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Find video protocols related to scientific articles indexed in Pubmed.
Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.
Wei-Yu Lin, Nicola J Camp, Maya Ghoussaini, Jonathan Beesley, Kyriaki Michailidou, John L Hopper, Carmel Apicella, Melissa C Southey, Jennifer Stone, Marjanka K Schmidt, Annegien Broeks, Laura J Van't Veer, Emiel J Th Rutgers, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Peter A Fasching, Lothar Haeberle, Arif B Ekici, Matthias W Beckmann, Julian Peto, Isabel Dos-Santos-Silva, Olivia Fletcher, Nichola Johnson, Manjeet K Bolla, Qin Wang, Joe Dennis, Elinor J Sawyer, Timothy Cheng, Ian Tomlinson, Michael J Kerin, Nicola Miller, Frederik Marme, Harald M Surowy, Barbara Burwinkel, Pascal Guénel, Thérèse Truong, Florence Menegaux, Claire Mulot, Stig E Bojesen, Børge G Nordestgaard, Sune F Nielsen, Henrik Flyger, Javier Benitez, M Pilar Zamora, José Ignacio Arias Perez, Primitiva Menéndez, Anna González-Neira, Guillermo Pita, M Rosario Alonso, Nuria Alvarez, Daniel Herrero, Hoda Anton-Culver, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Alfons Meindl, Peter Lichtner, Rita K Schmutzler, Bertram Müller-Myhsok, Hiltrud Brauch, Thomas Brüning, Yon-Dschun Ko, , Daniel C Tessier, Daniel Vincent, Francois Bacot, Heli Nevanlinna, Kristiina Aittomäki, Carl Blomqvist, Sofia Khan, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Akiyo Horio, Natalia V Bogdanova, Natalia N Antonenkova, Thilo Dörk, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Anna H Wu, Chiu-Chen Tseng, David Van Den Berg, Daniel O Stram, Patrick Neven, Els Wauters, Hans Wildiers, Diether Lambrechts, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Bernardo Bonanni, Fergus J Couch, Xianshu Wang, Celine Vachon, Kristen Purrington, Graham G Giles, Roger L Milne, Catriona McLean, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Jacques Simard, Mark S Goldberg, France Labrèche, Martine Dumont, Soo Hwang Teo, Cheng Har Yip, Norhashimah Hassan, Eranga Nishanthie Vithana, Vessela Kristensen, Wei Zheng, Sandra Deming-Halverson, Martha J Shrubsole, Jirong Long, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Saila Kauppila, Irene L Andrulis, Julia A Knight, Gord Glendon, Sandrine Tchatchou, Peter Devilee, Robert A E M Tollenaar, Caroline Seynaeve, Christi J van Asperen, Montserrat Garcia-Closas, Jonine Figueroa, Jolanta Lissowska, Louise Brinton, Kamila Czene, Hatef Darabi, Mikael Eriksson, Judith S Brand, Maartje J Hooning, Antoinette Hollestelle, Ans M W van den Ouweland, Agnes Jager, Jingmei Li, Jianjun Liu, Keith Humphreys, Xiao-Ou Shu, Wei Lu, Yu-Tang Gao, Hui Cai, Simon S Cross, Malcolm W R Reed, William Blot, Lisa B Signorello, Qiuyin Cai, Paul D P Pharoah, Barbara Perkins, Mitul Shah, Fiona M Blows, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Mikael Hartman, Hui Miao, Kee Seng Chia, Thomas Choudary Putti, Ute Hamann, Craig Luccarini, Caroline Baynes, Shahana Ahmed, Mel Maranian, Catherine S Healey, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Susan Slager, Amanda E Toland, Drakoulis Yannoukakos, Chen-Yang Shen, Chia-Ni Hsiung, Pei-Ei Wu, Shian-Ling Ding, Alan Ashworth, Michael Jones, Nick Orr, Anthony J Swerdlow, Helen Tsimiklis, Enes Makalic, Daniel F Schmidt, Quang M Bui, Stephen J Chanock, David J Hunter, Rebecca Hein, Norbert Dahmen, Lars Beckmann, Kirsimari Aaltonen, Taru A Muranen, Tuomas Heikkinen, Astrid Irwanto, Nazneen Rahman, Clare A Turnbull, Quinten Waisfisz, Hanne E J Meijers-Heijboer, Muriel A Adank, Rob B van der Luijt, Per Hall, Georgia Chenevix-Trench, Alison Dunning, Douglas F Easton, Angela Cox.
Hum. Mol. Genet.
PUBLISHED: 08-28-2014
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Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10(-5). Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 × 10(-6)), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10(-9). Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis.
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Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.
Christine F Skibola, Sonja I Berndt, Joseph Vijai, Lucia Conde, Zhaoming Wang, Meredith Yeager, Paul I W de Bakker, Brenda M Birmann, Claire M Vajdic, Jia-Nee Foo, Paige M Bracci, Roel C H Vermeulen, Susan L Slager, Silvia de Sanjosé, Sophia S Wang, Martha S Linet, Gilles Salles, Qing Lan, Gianluca Severi, Henrik Hjalgrim, Tracy Lightfoot, Mads Melbye, Jian Gu, Hervé Ghesquières, Brian K Link, Lindsay M Morton, Elizabeth A Holly, Alex Smith, Lesley F Tinker, Lauren R Teras, Anne Kricker, Nikolaus Becker, Mark P Purdue, John J Spinelli, Yawei Zhang, Graham G Giles, Paolo Vineis, Alain Monnereau, Kimberly A Bertrand, Demetrius Albanes, Anne Zeleniuch-Jacquotte, Attilio Gabbas, Charles C Chung, Laurie Burdett, Amy Hutchinson, Charles Lawrence, Rebecca Montalvan, Liming Liang, Jinyan Huang, Baoshan Ma, Jianjun Liu, Hans-Olov Adami, Bengt Glimelius, Yuanqing Ye, Grzegorz S Nowakowski, Ahmet Dogan, Carrie A Thompson, Thomas M Habermann, Anne J Novak, Mark Liebow, Thomas E Witzig, George J Weiner, Maryjean Schenk, Patricia Hartge, Anneclaire J De Roos, Wendy Cozen, Degui Zhi, Nicholas K Akers, Jacques Riby, Martyn T Smith, Mortimer Lacher, Danylo J Villano, Ann Maria, Eve Roman, Eleanor Kane, Rebecca D Jackson, Kari E North, W Ryan Diver, Jenny Turner, Bruce K Armstrong, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadié, Anthony Staines, James McKay, Angela R Brooks-Wilson, Tongzhang Zheng, Theodore R Holford, Saioa Chamosa, Rudolph Kaaks, Rachel S Kelly, Bodil Ohlsson, Ruth C Travis, Elisabete Weiderpass, Jacqueline Clavel, Edward Giovannucci, Peter Kraft, Jarmo Virtamo, Patrizio Mazza, Pierluigi Cocco, Maria Grazia Ennas, Brian C H Chiu, Joseph F Fraumeni, Alexandra Nieters, Kenneth Offit, Xifeng Wu, James R Cerhan, Karin E Smedby, Stephen J Chanock, Nathaniel Rothman.
Am. J. Hum. Genet.
PUBLISHED: 07-17-2014
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Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DR?1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
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Noninvasive diagnosis of actionable mutations by deep sequencing of circulating free DNA in lung cancer from never-smokers: a proof-of-concept study from BioCAST/IFCT-1002.
Clin. Cancer Res.
PUBLISHED: 07-10-2014
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Tumor somatic mutation analysis is part of the standard management of metastatic lung cancer. However, physicians often have to deal with small biopsies and consequently with challenging mutation testing. Circulating free DNA (cfDNA) is a promising tool for accessing the tumor genome as a liquid biopsy. Here, we evaluated next-generation sequencing (NGS) on cfDNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations.
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Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.
James R Cerhan, Sonja I Berndt, Joseph Vijai, Hervé Ghesquières, James McKay, Sophia S Wang, Zhaoming Wang, Meredith Yeager, Lucia Conde, Paul I W de Bakker, Alexandra Nieters, David Cox, Laurie Burdett, Alain Monnereau, Christopher R Flowers, Anneclaire J De Roos, Angela R Brooks-Wilson, Qing Lan, Gianluca Severi, Mads Melbye, Jian Gu, Rebecca D Jackson, Eleanor Kane, Lauren R Teras, Mark P Purdue, Claire M Vajdic, John J Spinelli, Graham G Giles, Demetrius Albanes, Rachel S Kelly, Mariagrazia Zucca, Kimberly A Bertrand, Anne Zeleniuch-Jacquotte, Charles Lawrence, Amy Hutchinson, Degui Zhi, Thomas M Habermann, Brian K Link, Anne J Novak, Ahmet Dogan, Yan W Asmann, Mark Liebow, Carrie A Thompson, Stephen M Ansell, Thomas E Witzig, George J Weiner, Amelie S Veron, Diana Zelenika, Hervé Tilly, Corinne Haioun, Thierry Jo Molina, Henrik Hjalgrim, Bengt Glimelius, Hans-Olov Adami, Paige M Bracci, Jacques Riby, Martyn T Smith, Elizabeth A Holly, Wendy Cozen, Patricia Hartge, Lindsay M Morton, Richard K Severson, Lesley F Tinker, Kari E North, Nikolaus Becker, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadié, Anthony Staines, Tracy Lightfoot, Simon Crouch, Alex Smith, Eve Roman, W Ryan Diver, Kenneth Offit, Andrew Zelenetz, Robert J Klein, Danylo J Villano, Tongzhang Zheng, Yawei Zhang, Theodore R Holford, Anne Kricker, Jenny Turner, Melissa C Southey, Jacqueline Clavel, Jarmo Virtamo, Stephanie Weinstein, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Dimitrios Trichopoulos, Roel C H Vermeulen, Heiner Boeing, Anne Tjonneland, Emanuele Angelucci, Simonetta Di Lollo, Marco Rais, Brenda M Birmann, Francine Laden, Edward Giovannucci, Peter Kraft, Jinyan Huang, Baoshan Ma, Yuanqing Ye, Brian C H Chiu, Joshua Sampson, Liming Liang, Ju-Hyun Park, Charles C Chung, Dennis D Weisenburger, Nilanjan Chatterjee, Joseph F Fraumeni, Susan L Slager, Xifeng Wu, Silvia de Sanjosé, Karin E Smedby, Gilles Salles, Christine F Skibola, Nathaniel Rothman, Stephen J Chanock.
Nat. Genet.
PUBLISHED: 06-26-2014
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Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
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Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.
Roger L Milne, Barbara Burwinkel, Kyriaki Michailidou, Jose-Ignacio Arias-Perez, M Pilar Zamora, Primitiva Menéndez-Rodríguez, David Hardisson, Marta Mendiola, Anna González-Neira, Guillermo Pita, M Rosario Alonso, Joe Dennis, Qin Wang, Manjeet K Bolla, Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk Schoemaker, Yon-Dschun Ko, Hiltrud Brauch, Ute Hamann, , Irene L Andrulis, Julia A Knight, Gord Glendon, Sandrine Tchatchou, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Jingmei Li, Judith S Brand, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Diether Lambrechts, Gilian Peuteman, Marie-Rose Christiaens, Ann Smeets, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska-Bieniek, Katazyna Durda, Mikael Hartman, Miao Hui, Wei Yen Lim, Ching Wan Chan, Federick Marme, Rongxi Yang, Peter Bugert, Annika Lindblom, Sara Margolin, Montserrat Garcia-Closas, Stephen J Chanock, Jolanta Lissowska, Jonine D Figueroa, Stig E Bojesen, Børge G Nordestgaard, Henrik Flyger, Maartje J Hooning, Mieke Kriege, Ans M W van den Ouweland, Linetta B Koppert, Olivia Fletcher, Nichola Johnson, Isabel Dos-Santos-Silva, Julian Peto, Wei Zheng, Sandra Deming-Halverson, Martha J Shrubsole, Jirong Long, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Angela Cox, Simon S Cross, Malcolm W R Reed, Marjanka K Schmidt, Annegien Broeks, Sten Cornelissen, Linde Braaf, Daehee Kang, Ji-Yeob Choi, Sue K Park, Dong-Young Noh, Jacques Simard, Martine Dumont, Mark S Goldberg, France Labrèche, Peter A Fasching, Alexander Hein, Arif B Ekici, Matthias W Beckmann, Paolo Radice, Paolo Peterlongo, Jacopo Azzollini, Monica Barile, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, John L Hopper, Daniel F Schmidt, Enes Makalic, Melissa C Southey, Soo Hwang Teo, Cheng Har Yip, Kavitta Sivanandan, Wan-Ting Tay, Chen-Yang Shen, Chia-Ni Hsiung, Jyh-Cherng Yu, Ming-Feng Hou, Pascal Guénel, Thérèse Truong, Marie Sanchez, Claire Mulot, William Blot, Qiuyin Cai, Heli Nevanlinna, Taru A Muranen, Kristiina Aittomäki, Carl Blomqvist, Anna H Wu, Chiu-Chen Tseng, David Van Den Berg, Daniel O Stram, Natalia Bogdanova, Thilo Dörk, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Xiao-Ou Shu, Wei Lu, Yu-Tang Gao, Ben Zhang, Fergus J Couch, Amanda E Toland, Drakoulis Yannoukakos, Suleeporn Sangrajrang, James McKay, Xianshu Wang, Janet E Olson, Celine Vachon, Kristen Purrington, Gianluca Severi, Laura Baglietto, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Peter Devilee, Robert A E M Tollenaar, Caroline Seynaeve, Kamila Czene, Mikael Eriksson, Keith Humphreys, Hatef Darabi, Shahana Ahmed, Mitul Shah, Paul D P Pharoah, Per Hall, Graham G Giles, Javier Benitez, Alison M Dunning, Georgia Chenevix-Trench, Douglas F Easton.
Hum. Mol. Genet.
PUBLISHED: 06-18-2014
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Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.
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Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study.
Nichola Johnson, Frank Dudbridge, Nick Orr, Lorna Gibson, Michael E Jones, Minouk J Schoemaker, Elizabeth J Folkerd, Ben P Haynes, John L Hopper, Melissa C Southey, Gillian S Dite, Carmel Apicella, Marjanka K Schmidt, Annegien Broeks, Laura J Van T Veer, Femke Atsma, Kenneth Muir, Artitaya Lophatananon, Peter A Fasching, Matthias W Beckmann, Arif B Ekici, Stefan P Renner, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, Barbara Burwinkel, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Pascal Guénel, Thérèse Truong, Emilie Cordina, Florence Menegaux, Stig E Bojesen, Børge G Nordestgaard, Henrik Flyger, Roger Milne, M Pilar Zamora, José Ignacio Arias Perez, Javier Benitez, Leslie Bernstein, Hoda Anton-Culver, Argyrios Ziogas, Christina Clarke Dur, Hermann Brenner, Heiko Muller, Volker Arndt, Aida Karina Dieffenbach, Alfons Meindl, Joerg Heil, Claus R Bartram, Rita K Schmutzler, Hiltrud Brauch, Christina Justenhoven, Yon-Dschun Ko, Heli Nevanlinna, Taru A Muranen, Kristiina Aittomäki, Carl Blomqvist, Keitaro Matsuo, Thilo Dörk, Natalia V Bogdanova, Natalia N Antonenkova, Annika Lindblom, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Georgia Chenevix-Trench, Jonathan Beesley, Anna H Wu, David Van Den Berg, Chiu-Chen Tseng, Diether Lambrechts, Dominiek Smeets, Patrick Neven, Hans Wildiers, Jenny Chang-Claude, Anja Rudolph, Stefan Nickels, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Bernardo Bonanni, Valeria Pensotti, Fergus J Couch, Janet E Olson, Xianshu Wang, Zachary Fredericksen, Vernon S Pankratz, Graham G Giles, Gianluca Severi, Laura Baglietto, Chris Haiman, Jacques Simard, Mark S Goldberg, France Labrèche, Martine Dumont, Penny Soucy, Soo Teo, Cheng Har Yip, Sze Yee Phuah, Belinda K Cornes, Vessela N Kristensen, Grethe Grenaker Alnæs, Anne-Lise Børresen-Dale, Wei Zheng, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L Andrulis, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Peter Devillee, Jonine Figueroa, Stephen J Chanock, Jolanta Lissowska, Mark E Sherman, Per Hall, Nils Schoof, Maartje Hooning, Antoinette Hollestelle, Rogier A Oldenburg, Madeleine Tilanus-Linthorst, Jianjun Liu, Angie Cox, Ian W Brock, Malcolm Wr Reed, Simon S Cross, William Blot, Lisa B Signorello, Paul Dp Pharoah, Alison M Dunning, Mitul Shah, Daehee Kang, Dong-Young Noh, Sue K Park, Ji-Yeob Choi, Mikael Hartman, Hui Miao, Wei Yen Lim, Anthony Tang, Ute Hamann, Asta Försti, Thomas Rüdiger, Hans Ulrich Ulmer, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Susan Slager, Amanda E Toland, Celine Vachon, Drakoulis Yannoukakos, Chen-Yang Shen, Jyh-Cherng Yu, Chiun-Sheng Huang, Ming-Feng Hou, Anna González-Neira, Daniel C Tessier, Daniel Vincent, Francois Bacot, Craig Luccarini, Joe Dennis, Kyriaki Michailidou, Manjeet K Bolla, Jean Wang, Douglas F Easton, Montserrat Garcia-Closas, Mitch Dowsett, Alan Ashworth, Anthony J Swerdlow, Julian Peto, Isabel Dos Santos Silva, Olivia Fletcher.
Breast Cancer Res.
PUBLISHED: 05-26-2014
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We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age <=50 years.
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Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.
Nat. Genet.
PUBLISHED: 05-08-2014
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We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 × 10(-20)) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 × 10(-13)). We also showed an association between common variation at 3q28 (TP63, rs13314271, OR = 1.13, P = 7.22 × 10(-10)) and lung adenocarcinoma that had been previously reported only in Asians. These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis. Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants with substantive effects on cancer risk from preexisting genome-wide association study data.
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TP53, MSH4, and LATS1 germline mutations in a family with clustering of nervous system tumors.
Am. J. Pathol.
PUBLISHED: 04-17-2014
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Exome DNA sequencing of blood samples from a Li-Fraumeni family with a TP53 germline mutation (codon 236 deletion) and multiple nervous system tumors revealed additional germline mutations. Missense mutations in the MSH4 DNA repair gene (c.2480T>A; p.I827N) were detected in three patients with gliomas (two anaplastic astrocytomas, two glioblastomas). Two family members without a TP53 germline mutation who developed peripheral schwannomas also carried the MSH4 germline mutation, and in addition, a germline mutation of the LATS1 gene (c.286C>T; p.R96W). LATS1 is a downstream mediator of the NF2, but has not previously been found to be related to schwannomas. We therefore screened the entire coding sequence of the LATS1 gene in 65 sporadic schwannomas, 12 neurofibroma/schwannoma hybrid tumors, and 4 cases of schwannomatosis. We only found a single base deletion at codon 827 (exon 5) in a spinal schwannoma, leading to a stop at codon 835 (c.2480delG; p.*R827Kfs*8). Mutational loss of LATS1 function may thus play a role in some inherited schwannomas, but only exceptionally in sporadic schwannomas. This is the first study reporting a germline MSH4 mutation. Since it was present in all patients, it may have contributed to the subsequent acquisition of TP53 and LATS1 germline mutations.
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Nationwide dissemination of contingency management: the Veterans Administration initiative.
Am J Addict
PUBLISHED: 04-15-2014
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Contingency management (CM) is an empirically validated intervention but one not often applied in practice settings in the US.
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Genetic variants in DNA repair pathways and risk of upper aerodigestive tract cancers: combined analysis of data from two genome-wide association studies in European populations.
Carcinogenesis
PUBLISHED: 03-21-2014
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DNA repair pathways are good candidates for upper aerodigestive tract cancer susceptibility because of their critical role in maintaining genome integrity. We have selected 13 pathways involved in DNA repair representing 212 autosomal genes. To assess the role of these pathways and their associated genes, two European data sets from the International Head and Neck Cancer Epidemiology consortium were pooled, totaling 1954 cases and 3121 controls, with documented demographic, lifetime alcohol and tobacco consumption information. We applied an innovative approach that tests single nucleotide polymorphism (SNP)-sets within DNA repair pathways and then within genes belonging to the significant pathways. We showed an association between the polymerase pathway and oral cavity/pharynx cancers (P-corrected = 4.45 × 10(-) (2)), explained entirely by the association with one SNP, rs1494961 (P = 2.65 × 10(-) (4)), a missense mutation V306I in the second exon of HELQ gene. We also found an association between the cell cycle regulation pathway and esophagus cancer (P-corrected = 1.48 × 10(-) (2)), explained by three SNPs located within or near CSNK1E gene: rs1534891 (P = 1.27 × 10(-) (4)), rs7289981 (P = 3.37 × 10(-) (3)) and rs13054361 (P = 4.09 × 10(-) (3)). As a first attempt to investigate pathway-level associations, our results suggest a role of specific DNA repair genes/pathways in specific upper aerodigestive tract cancer sites.
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Social network correlates of participation in telephone continuing care for alcohol dependence.
Am J Addict
PUBLISHED: 03-15-2014
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Research on face-to-face treatment for substance misuse suggests that patients' social networks may impact treatment entry and participation, but there has been no similar research on entry and participation in telephone-based continuing care. We examined whether alcohol-specific social support predicted engagement and participation in telephone continuing care for alcohol dependence, and whether treatment participation resulted in beneficial changes in participants' social networks.
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Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.
Maya Ghoussaini, Stacey L Edwards, Kyriaki Michailidou, Silje Nord, Richard Cowper-Sal Lari, Kinjal Desai, Siddhartha Kar, Kristine M Hillman, Susanne Kaufmann, Dylan M Glubb, Jonathan Beesley, Joe Dennis, Manjeet K Bolla, Qin Wang, Ed Dicks, Qi Guo, Marjanka K Schmidt, Mitul Shah, Robert Luben, Judith Brown, Kamila Czene, Hatef Darabi, Mikael Eriksson, Daniel Klevebring, Stig E Bojesen, Børge G Nordestgaard, Sune F Nielsen, Henrik Flyger, Diether Lambrechts, Bernard Thienpont, Patrick Neven, Hans Wildiers, Annegien Broeks, Laura J Van't Veer, Emiel J Th Rutgers, Fergus J Couch, Janet E Olson, Emily Hallberg, Celine Vachon, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Julian Peto, Isabel Dos-Santos-Silva, Lorna Gibson, Heli Nevanlinna, Taru A Muranen, Kristiina Aittomäki, Carl Blomqvist, Per Hall, Jingmei Li, Jianjun Liu, Keith Humphreys, Daehee Kang, Ji-Yeob Choi, Sue K Park, Dong-Young Noh, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Yasushi Yatabe, Pascal Guénel, Thérèse Truong, Florence Menegaux, Marie Sanchez, Barbara Burwinkel, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Anna H Wu, Chiu-Chen Tseng, David Van Den Berg, Daniel O Stram, Javier Benitez, M Pilar Zamora, Jose Ignacio Arias Perez, Primitiva Menéndez, Xiao-Ou Shu, Wei Lu, Yu-Tang Gao, Qiuyin Cai, Angela Cox, Simon S Cross, Malcolm W R Reed, Irene L Andrulis, Julia A Knight, Gord Glendon, Sandrine Tchatchou, Elinor J Sawyer, Ian Tomlinson, Michael J Kerin, Nicola Miller, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Annika Lindblom, Sara Margolin, Soo Hwang Teo, Cheng Har Yip, Daphne S C Lee, Tien Y Wong, Maartje J Hooning, John W M Martens, J Margriet Collée, Carolien H M van Deurzen, John L Hopper, Melissa C Southey, Helen Tsimiklis, Miroslav K Kapuscinski, Chen-Yang Shen, Pei-Ei Wu, Jyh-Cherng Yu, Shou-Tung Chen, Grethe Grenaker Alnæs, Anne-Lise Borresen-Dale, Graham G Giles, Roger L Milne, Catriona McLean, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Mikael Hartman, Hui Miao, Shaik Ahmad Bin Syed Buhari, Yik Ying Teo, Peter A Fasching, Lothar Haeberle, Arif B Ekici, Matthias W Beckmann, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk J Schoemaker, Montserrat Garcia-Closas, Jonine Figueroa, Stephen J Chanock, Jolanta Lissowska, Jacques Simard, Mark S Goldberg, France Labrèche, Martine Dumont, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Hiltrud Brauch, Thomas Brüning, Yon-Dschun Koto, Paolo Radice, Paolo Peterlongo, Bernardo Bonanni, Sara Volorio, Thilo Dörk, Natalia V Bogdanova, Sonja Helbig, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Peter Devilee, Robert A E M Tollenaar, Caroline Seynaeve, Christi J van Asperen, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Susan Slager, Amanda E Toland, Christine B Ambrosone, Drakoulis Yannoukakos, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Ute Hamann, Diana Torres, Wei Zheng, Jirong Long, Hoda Anton-Culver, Susan L Neuhausen, Craig Luccarini, Caroline Baynes, Shahana Ahmed, Mel Maranian, Catherine S Healey, Anna González-Neira, Guillermo Pita, M Rosario Alonso, Nuria Alvarez, Daniel Herrero, Daniel C Tessier, Daniel Vincent, Francois Bacot, Ines de Santiago, Jason Carroll, Carlos Caldas, Melissa A Brown, Mathieu Lupien, Vessela N Kristensen, Paul D P Pharoah, Georgia Chenevix-Trench, Juliet D French, Douglas F Easton, Alison M Dunning, .
Nat Commun
PUBLISHED: 03-12-2014
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GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.
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Genome-wide association study reveals two new risk loci for bipolar disorder.
Nat Commun
PUBLISHED: 01-29-2014
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Bipolar disorder (BD) is a common and highly heritable mental illness and genome-wide association studies (GWAS) have robustly identified the first common genetic variants involved in disease aetiology. The data also provide strong evidence for the presence of multiple additional risk loci, each contributing a relatively small effect to BD susceptibility. Large samples are necessary to detect these risk loci. Here we present results from the largest BD GWAS to date by investigating 2.3 million single-nucleotide polymorphisms (SNPs) in a sample of 24,025 patients and controls. We detect 56 genome-wide significant SNPs in five chromosomal regions including previously reported risk loci ANK3, ODZ4 and TRANK1, as well as the risk locus ADCY2 (5p15.31) and a region between MIR2113 and POU3F2 (6q16.1). ADCY2 is a key enzyme in cAMP signalling and our finding provides new insights into the biological mechanisms involved in the development of BD.
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Modelling mutational landscapes of human cancers in vitro.
Sci Rep
PUBLISHED: 01-10-2014
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Experimental models that recapitulate mutational landscapes of human cancers are needed to decipher the rapidly expanding data on human somatic mutations. We demonstrate that mutation patterns in immortalised cell lines derived from primary murine embryonic fibroblasts (MEFs) exposed in vitro to carcinogens recapitulate key features of mutational signatures observed in human cancers. In experiments with several cancer-causing agents we obtained high genome-wide concordance between human tumour mutation data and in vitro data with respect to predominant substitution types, strand bias and sequence context. Moreover, we found signature mutations in well-studied human cancer driver genes. To explore endogenous mutagenesis, we used MEFs ectopically expressing activation-induced cytidine deaminase (AID) and observed an excess of AID signature mutations in immortalised cell lines compared to their non-transgenic counterparts. MEF immortalisation is thus a simple and powerful strategy for modelling cancer mutation landscapes that facilitates the interpretation of human tumour genome-wide sequencing data.
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Genetic variants in nicotine addiction and alcohol metabolism genes, oral cancer risk and the propensity to smoke and drink alcohol: a replication study in India.
PLoS ONE
PUBLISHED: 01-01-2014
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Genetic variants in nicotinic acetylcholine receptor and alcohol metabolism genes have been associated with propensity to smoke tobacco and drink alcohol, respectively, and also implicated in genetic susceptibility to head and neck cancer. In addition to smoking and alcohol, tobacco chewing is an important oral cancer risk factor in India. It is not known if these genetic variants influence propensity or oral cancer susceptibility in the context of this distinct etiology.
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Disease Control and Safety of Belimumab Plus Standard Therapy Over 7 Years in Patients with Systemic Lupus Erythematosus.
J. Rheumatol.
PUBLISHED: 11-01-2013
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To evaluate the efficacy/safety of belimumab plus standard therapy in patients (n = 449) with active systemic lupus erythematosus (SLE) treated up to 7 years (n = 177 currently ongoing).
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An adaptive approach for identifying cocaine dependent patients who benefit from extended continuing care.
J Consult Clin Psychol
PUBLISHED: 09-16-2013
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Objective: Study tested whether cocaine dependent patients using cocaine or alcohol at intake or in the first few weeks of intensive outpatient treatment would benefit more from extended continuing care than patients abstinent during this period. The effect of incentives for continuing care attendance was also examined. Method: Participants (N = 321) were randomized to treatment as usual (TAU), TAU and telephone monitoring and counseling (TMC), or TAU and TMC plus incentives (TMC+). The primary outcomes were (a) abstinence from all drugs and heavy alcohol use and (b) cocaine urine toxicology. Follow-ups were at 3, 6, 9, 12, 18, and 24 months. Results: Cocaine and alcohol use at intake or early in treatment predicted worse outcomes on both measures (ps ? .0002). Significant effects favoring TMC over TAU on the abstinence composite were obtained in participants who used cocaine (odds ratio [OR] = 1.95 [1.02, 3.73]) or alcohol (OR = 2.47 [1.28, 4.78]) at intake or early in treatment. A significant effect favoring TMC+ over TAU on cocaine urine toxicology was obtained in those using cocaine during that period (OR = 0.55 [0.31, 0.95]). Conversely, there were no treatment effects in participants abstinent at baseline and no overall treatment main effects. Incentives almost doubled the number of continuing care sessions received but did not further improve outcomes. Conclusion: An adaptive approach for cocaine dependence in which extended continuing care is provided only to patients who are using cocaine or alcohol at intake or early in treatment improves outcomes in this group while reducing burden and costs in lower risk patients. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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Fine-Scale Mapping of the FGFR2 Breast Cancer Risk Locus: Putative Functional Variants Differentially Bind FOXA1 and E2F1.
Kerstin B Meyer, Martin O'Reilly, Kyriaki Michailidou, Saskia Carlebur, Stacey L Edwards, Juliet D French, Radhika Prathalingham, Joe Dennis, Manjeet K Bolla, Qin Wang, Ines de Santiago, John L Hopper, Helen Tsimiklis, Carmel Apicella, Melissa C Southey, Marjanka K Schmidt, Annegien Broeks, Laura J van 't Veer, Frans B Hogervorst, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Peter A Fasching, Michael P Lux, Arif B Ekici, Matthias W Beckmann, Julian Peto, Isabel Dos Santos Silva, Olivia Fletcher, Nichola Johnson, Elinor J Sawyer, Ian Tomlinson, Michael J Kerin, Nicola Miller, Federick Marme, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Thérèse Truong, Pierre Laurent-Puig, Florence Menegaux, Stig E Bojesen, Børge G Nordestgaard, Sune F Nielsen, Henrik Flyger, Roger L Milne, M Pilar Zamora, Jose I Arias, Javier Benitez, Susan Neuhausen, Hoda Anton-Culver, Argyrios Ziogas, Christina C Dur, Hermann Brenner, Heiko Muller, Volker Arndt, Christa Stegmaier, Alfons Meindl, Rita K Schmutzler, Christoph Engel, Nina Ditsch, Hiltrud Brauch, Thomas Brüning, Yon-Dschun Ko, , Heli Nevanlinna, Taru A Muranen, Kristiina Aittomäki, Carl Blomqvist, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Yasushi Yatabe, Thilo Dörk, Sonja Helbig, Natalia V Bogdanova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Georgia Chenevix-Trench, Anna H Wu, Chiu-Chen Tseng, David Van Den Berg, Daniel O Stram, Diether Lambrechts, Bernard Thienpont, Marie-Rose Christiaens, Ann Smeets, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Bernardo Bonanni, Loris Bernard, Fergus J Couch, Janet E Olson, Xianshu Wang, Kristen Purrington, Graham G Giles, Gianluca Severi, Laura Baglietto, Catriona McLean, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Jacques Simard, Mark S Goldberg, France Labrèche, Martine Dumont, Soo-Hwang Teo, Cheng-Har Yip, Sze-Yee Phuah, Vessela Kristensen, Grethe Grenaker Alnæs, Anne-Lise Børresen-Dale, Wei Zheng, Sandra Deming-Halverson, Martha Shrubsole, Jirong Long, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Saila Kauppila, Irene L Andrulis, Julia A Knight, Gord Glendon, Sandrine Tchatchou, Peter Devilee, Robert A E M Tollenaar, Caroline M Seynaeve, Montserrat Garcia-Closas, Jonine Figueroa, Stephen J Chanock, Jolanta Lissowska, Kamila Czene, Hartef Darabi, Kimael Eriksson, Maartje J Hooning, John W M Martens, Ans M W van den Ouweland, Carolien H M van Deurzen, Per Hall, Jingmei Li, Jianjun Liu, Keith Humphreys, Xiao-Ou Shu, Wei Lu, Yu-Tang Gao, Hui Cai, Angela Cox, Malcolm W R Reed, William Blot, Lisa B Signorello, Qiuyin Cai, Paul D P Pharoah, Maya Ghoussaini, Patricia Harrington, Jonathan Tyrer, Daehee Kang, Ji-Yeob Choi, Sue K Park, Dong-Young Noh, Mikael Hartman, Miao Hui, Wei-Yen Lim, Shaik A Buhari, Ute Hamann, Asta Försti, Thomas Rüdiger, Hans-Ulrich Ulmer, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska, Katarzyna Durda, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Celine Vachon, Susan Slager, Florentia Fostira, Robert Pilarski, Chen-Yang Shen, Chia-Ni Hsiung, Pei-Ei Wu, Ming-Feng Hou, Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk J Schoemaker, Bruce A J Ponder, Alison M Dunning, Douglas F Easton.
Am. J. Hum. Genet.
PUBLISHED: 08-01-2013
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The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus. Within risk signals 1 and 3, genetic analysis identified five and two variants, respectively, highly correlated with the most strongly associated SNPs. By using a combination of genetic fine mapping, data on DNase hypersensitivity, and electrophoretic mobility shift assays to study protein-DNA binding, we identified rs35054928, rs2981578, and rs45631563 as putative functional SNPs. Chromatin immunoprecipitation showed that FOXA1 preferentially bound to the risk-associated allele (C) of rs2981578 and was able to recruit ER? to this site in an allele-specific manner, whereas E2F1 preferentially bound the risk variant of rs35054928. The risk alleles were preferentially found in open chromatin and bound by Ser5 phosphorylated RNA polymerase II, suggesting that the risk alleles are associated with changes in transcription. Chromatin conformation capture demonstrated that the risk region was able to interact with the promoter of FGFR2, the likely target gene of this risk region. A role for FOXA1 in mediating breast cancer susceptibility at this locus is consistent with the finding that the FGFR2 risk locus primarily predisposes to estrogen-receptor-positive disease.
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Who benefits from extended continuing care for cocaine dependence?
Addict Behav
PUBLISHED: 06-14-2013
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The goal of this study was to determine which cocaine dependent patients engaged in an intensive outpatient program (IOP) were most likely to benefit from extended continuing care (24months). Participants (N=321) were randomized to: IOP treatment as usual (TAU), TAU plus Telephone Monitoring and Counseling (TMC), or TAU plus TMC plus incentives for session attendance (TMC+). Potential moderators examined were gender, stay in a controlled environment prior to IOP, number of prior drug treatments, and seven measures of progress toward IOP goals. Outcomes were: (1) abstinence from all drugs and heavy alcohol use, and (2) cocaine urine toxicology. Follow-ups were conducted at 3, 6, 9, 12, 18, and 24months post-baseline. Results indicated that there were significant effects favoring TMC+ over TAU on the cocaine urine toxicology outcome for participants in a controlled environment prior to IOP and for those with no days of depression early in IOP. Trends were obtained favoring TMC over TAU for those in a controlled environment (cocaine urine toxicology outcome) or with high family/social problem severity (abstinence composite outcome), and TMC+ over TAU for those with high family/social problem severity or high self-efficacy (cocaine urine toxicology outcome). None of the other potential moderator effects examined reached the level of a trend. These results generally do not suggest that patients with greater problem severity or poorer performance early in treatment on the measures considered in this report will benefit to a greater degree from extended continuing care.
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Telephone monitoring and support after discharge from residential PTSD treatment: a randomized controlled trial.
Psychiatr Serv
PUBLISHED: 06-14-2013
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This study assessed whether adding a telephone care management protocol to usual aftercare improved the outcomes of veterans in the year after they were discharged from residential treatment for posttraumatic stress disorder (PTSD).
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Enhanced continuing care provided in parallel to intensive outpatient treatment does not improve outcomes for patients with cocaine dependence.
J Stud Alcohol Drugs
PUBLISHED: 06-07-2013
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This study tested whether the addition of an enhanced continuing care (ECC) intervention that combined in-person and telephone sessions and began in the first week of treatment improved outcomes for cocaine-dependent patients entering an intensive outpatient program (IOP).
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Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in Belarusian children exposed to radiation.
Int. J. Cancer
PUBLISHED: 05-03-2013
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A dramatic increase in the incidence of papillary thyroid carcinoma (PTC) after childhood exposure to ionizing radiation from the Chernobyl nuclear accident has been described as the largest number of tumors of one type due to one cause that have ever occurred. inter-individual variations in response to radiation have been documented and the role of genetics in sporadic PTC is well established, suggesting that genetic factors may also affect the risk of radiation-related PTC. To investigate how environmental and host factors interplay to modify PTC risk, we genotyped 83 cases and 324 matched controls sampled from children living in the area contaminated by fallout from the Chernobyl power plant accident for 19 polymorphisms previously associated with PTC, thyroid biology or radiation-induced second primary tumors. Significant association with PTC was found for rs1801516 (D1853N) in ATM (odds ratio (OR) = 0.34, 95% confidence interval (CI) 0.16, 0.73) and rs1867277 in the promoter region of FOXE1 (OR = 1.55, 95% CI 1.03, 2.34). Analysis of additional polymorphisms confirmed the association between these two genes and PTC. Our findings suggest that both DNA double-strand break repair pathway and thyroid morphogenesis pathway or dysregulation of thyroid differentiated state maintenance are involved in the etiology of PTC, and that the studied genetic polymorphisms and radiation dose appear to act as independent multiplicative risk factors for PTC.
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A universal open-source Electronic Laboratory Notebook.
Bioinformatics
PUBLISHED: 05-03-2013
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Laboratory notebooks remain crucial to the activities of research communities. With the increase in generation of electronic data within both wet and dry analytical laboratories and new technologies providing more efficient means of communication, Electronic Laboratory Notebooks (ELN) offer equivalent record keeping to paper-based laboratory notebooks (PLN). They additionally allow more efficient mechanisms for data sharing and retrieval, which explains the growing number of commercial ELNs available varying in size and scope but all are increasingly accepted and used by the scientific community. The International Agency for Research on Cancer (IARC) having already an LIMS and a Biobank Management System for respectively laboratory workflows and sample management, we have developed a free multidisciplinary ELN specifically dedicated to work notes that will be flexible enough to accommodate different types of data. Availability and implementation: Information for installation of our freeware ELN with source codes customizations are detailed in supplementary data.
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Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.
Sonja I Berndt, Christine F Skibola, Vijai Joseph, Nicola J Camp, Alexandra Nieters, Zhaoming Wang, Wendy Cozen, Alain Monnereau, Sophia S Wang, Rachel S Kelly, Qing Lan, Lauren R Teras, Nilanjan Chatterjee, Charles C Chung, Meredith Yeager, Angela R Brooks-Wilson, Patricia Hartge, Mark P Purdue, Brenda M Birmann, Bruce K Armstrong, Pierluigi Cocco, Yawei Zhang, Gianluca Severi, Anne Zeleniuch-Jacquotte, Charles Lawrence, Laurie Burdette, Jeffrey Yuenger, Amy Hutchinson, Kevin B Jacobs, Timothy G Call, Tait D Shanafelt, Anne J Novak, Neil E Kay, Mark Liebow, Alice H Wang, Karin E Smedby, Hans-Olov Adami, Mads Melbye, Bengt Glimelius, Ellen T Chang, Martha Glenn, Karen Curtin, Lisa A Cannon-Albright, Brandt Jones, W Ryan Diver, Brian K Link, George J Weiner, Lucia Conde, Paige M Bracci, Jacques Riby, Elizabeth A Holly, Martyn T Smith, Rebecca D Jackson, Lesley F Tinker, Yolanda Benavente, Nikolaus Becker, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadié, James McKay, Anthony Staines, Kari G Rabe, Sara J Achenbach, Celine M Vachon, Lynn R Goldin, Sara S Strom, Mark C Lanasa, Logan G Spector, Jose F Leis, Julie M Cunningham, J Brice Weinberg, Vicki A Morrison, Neil E Caporaso, Aaron D Norman, Martha S Linet, Anneclaire J De Roos, Lindsay M Morton, Richard K Severson, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Dimitrios Trichopoulos, Giovanna Masala, Elisabete Weiderpass, Maria-Dolores Chirlaque, Roel C H Vermeulen, Ruth C Travis, Graham G Giles, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Jacqueline Clavel, Tongzhang Zheng, Theodore R Holford, Kenneth Offit, Andrew Zelenetz, Robert J Klein, John J Spinelli, Kimberly A Bertrand, Francine Laden, Edward Giovannucci, Peter Kraft, Anne Kricker, Jenny Turner, Claire M Vajdic, Maria Grazia Ennas, Giovanni M Ferri, Lucia Miligi, Liming Liang, Joshua Sampson, Simon Crouch, Ju-Hyun Park, Kari E North, Angela Cox, John A Snowden, Josh Wright, Angel Carracedo, Carlos Lopez-Otin, Sílvia Beà, Itziar Salaverria, David Martín-Garcia, Elias Campo, Joseph F Fraumeni, Silvia de Sanjosé, Henrik Hjalgrim, James R Cerhan, Stephen J Chanock, Nathaniel Rothman, Susan L Slager.
Nat. Genet.
PUBLISHED: 05-02-2013
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Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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The FOXE1 locus is a major genetic determinant for familial nonmedullary thyroid carcinoma.
Int. J. Cancer
PUBLISHED: 04-29-2013
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Thyroid cancer is the most common endocrine malignancy and nonmedullary thyroid carcinoma (NMTC) represents 90% of all cases. NMTC risk in first-degree relatives of affected cases is elevated fivefold to ninefold. Familial NMTC (FNMTC) accounts for about 3-7% of all thyroid tumors and is a more aggressive clinical entity than its sporadic counterparts. Linkage analysis on high-risk families performed a decade ago mapped several susceptibility loci, but did not lead to the identification of high-penetrance causal germline mutations. More recently, a genome-wide association study (GWAS) identified common single nucleotide polymorphisms (SNPs) affecting the risk of sporadic NMTC. We sought to verify if the newly identified genetic risk factors for NMTC are relevant for FNMTC as well. We genotyped 23 SNPs at 11 candidate loci in 672 subjects belonging to 133 pedigrees with at least two NMTC cases. Statistical analysis was performed using family-based association tests, modified quasi-likelihood score and logistic-normal models. SNPs at 9q22.33 near FOXE1 showed convincing evidence of association with NMTC risk in these high-risk families. The other tested loci resulted negative. These findings confirm the importance of the SNPs identified by recent GWAS on sporadic NMTC on FNMTC as well. However, the proposed FOXE1 causal variants do not show the strongest association signal. Moreover, mutation screening of the FOXE1 coding sequence in the FNMTC cases did not identify rarer causal variants, suggesting that other yet unidentified variants at this locus are involved in FNMTC etiology.
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A Randomized Clinical Trial of Alcohol Care Management Delivered in Department of Veterans Affairs Primary Care Clinics Versus Specialty Addiction Treatment.
J Gen Intern Med
PUBLISHED: 04-22-2013
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Alcohol use disorder is one of the leading causes of disability worldwide. Despite the availability of efficacious treatments, few individuals with an alcohol use disorder are actively engaged in treatment. Available evidence suggests that primary care may play a crucial role in the identification of patients with an alcohol use disorder, delivery of interventions, and the success of treatment.
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The effects of cannabis use expectancies on self-initiated cannabis cessation.
Addiction
PUBLISHED: 04-19-2013
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To prospectively investigate the relation between cannabis use expectancies and cannabis use prior to and during a self-initiated cannabis cessation attempt.
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A new method for producing transgenic birds via direct in vivo transfection of primordial germ cells.
Transgenic Res.
PUBLISHED: 03-25-2013
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Traditional methods of avian transgenesis involve complex manipulations involving either retroviral infection of blastoderms or the ex vivo manipulation of primordial germ cells (PGCs) followed by injection of the cells back into a recipient embryo. Unlike in mammalian systems, avian embryonic PGCs undergo a migration through the vasculature on their path to the gonad where they become the sperm or ova producing cells. In a development which simplifies the procedure of creating transgenic chickens we have shown that PGCs are directly transfectable in vivo using commonly available transfection reagents. We used Lipofectamine 2000 complexed with Tol2 transposon and transposase plasmids to stably transform PGCs in vivo generating transgenic offspring that express a reporter gene carried in the transposon. The process has been shown to be highly effective and as robust as the other methods used to create germ-line transgenic chickens while substantially reducing time, infrastructure and reagents required. The method described here defines a simple direct approach for transgenic chicken production, allowing researchers without extensive PGC culturing facilities or skills with retroviruses to produce transgenic chickens for wide-ranging applications in research, biotechnology and agriculture.
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Epstein - Barr virus transforming protein LMP-1 alters B cells gene expression by promoting accumulation of the oncoprotein ?Np73?.
PLoS Pathog.
PUBLISHED: 03-14-2013
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Many studies have proved that oncogenic viruses develop redundant mechanisms to alter the functions of the tumor suppressor p53. Here we show that Epstein-Barr virus (EBV), via the oncoprotein LMP-1, induces the expression of ?Np73?, a strong antagonist of p53. This phenomenon is mediated by the LMP-1 dependent activation of c-Jun NH2-terminal kinase 1 (JNK-1) which in turn favours the recruitment of p73 to ?Np73? promoter. A specific chemical inhibitor of JNK-1 or silencing JNK-1 expression strongly down-regulated ?Np73? mRNA levels in LMP-1-containing cells. Accordingly, LMP-1 mutants deficient to activate JNK-1 did not induce ?Np73? accumulation. The recruitment of p73 to the ?Np73? promoter correlated with the displacement of the histone-lysine N-methyltransferase EZH2 which is part of the transcriptional repressive polycomb 2 complex. Inhibition of ?Np73? expression in lymphoblastoid cells (LCLs) led to the stimulation of apoptosis and up-regulation of a large number of cellular genes as determined by whole transcriptome shotgun sequencing (RNA-seq). In particular, the expression of genes encoding products known to play anti-proliferative/pro-apoptotic functions, as well as genes known to be deregulated in different B cells malignancy, was altered by ?Np73? down-regulation. Together, these findings reveal a novel EBV mechanism that appears to play an important role in the transformation of primary B cells.
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Genome-wide association study of susceptibility loci for cervical cancer.
J. Natl. Cancer Inst.
PUBLISHED: 03-12-2013
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Cervical carcinoma has a heritable genetic component, but the genetic basis of cervical cancer is still not well understood.
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Index cholecystectomy: a continuing challenge for a provincial hospital.
N. Z. Med. J.
PUBLISHED: 03-07-2013
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To review the management of acute gallstone disease at a provincial New Zealand centre and compare to current national/international practice.
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Factors in sustained recovery from cocaine dependence.
J Subst Abuse Treat
PUBLISHED: 02-25-2013
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The goal was to identify factors that predicted sustained cocaine abstinence and transitions from cocaine use to abstinence over 24 months. Data from baseline assessments and multiple follow-ups were obtained from three studies of continuing care for patients in intensive outpatient programs (IOPs). In the combined sample, remaining cocaine abstinent and transitioning into abstinence at the next follow-up were predicted by older age, less education, and less cocaine and alcohol use at baseline, and by higher self-efficacy, commitment to abstinence, better social support, lower depression, and lower scores on other problem severity measures assessed during the follow-up. In addition, higher self-help participation, self-help beliefs, readiness to change, and coping assessed during the follow-up predicted transitions from cocaine use to abstinence. These results were stable over 24 months. Commitment to abstinence, self-help behaviors and beliefs, and self-efficacy contributed independently to the prediction of cocaine use transitions. Implications for treatment are discussed.
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Training workshops positively impact beliefs about contingency management in a nationwide dissemination effort.
J Subst Abuse Treat
PUBLISHED: 02-22-2013
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In 2011, the Veterans Administration called for nationwide implementation of contingency management (CM) in its intensive outpatient substance use disorders treatment programs, and this study evaluated the impact of the initial 1 and ½ day training workshops on knowledge and perceptions about CM among 159 clinical leaders from 113 clinics. Workshop attendance significantly increased CM-related knowledge (d=1.88) and changed attendees perceptions of CM (ds=0.26-0.74). Endorsement of barriers to CM adoption decreased and positive impressions of CM increased. These perceptions about CM emerged as key correlates of post-training preparedness to implement CM. Results suggest that training workshops can be an effective avenue for increasing CM-related knowledge, as well as addressing persistent misperceptions about CM that may impede adoption efforts. Continued efforts to introduce educational materials and offer training and consultation opportunities may increase understanding about this evidence-based intervention among clinicians, thereby leading to improved patient outcomes.
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Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.
Stig E Bojesen, Karen A Pooley, Sharon E Johnatty, Jonathan Beesley, Kyriaki Michailidou, Jonathan P Tyrer, Stacey L Edwards, Hilda A Pickett, Howard C Shen, Chanel E Smart, Kristine M Hillman, Phuong L Mai, Kate Lawrenson, Michael D Stutz, Yi Lu, Rod Karevan, Nicholas Woods, Rebecca L Johnston, Juliet D French, Xiaoqing Chen, Maren Weischer, Sune F Nielsen, Melanie J Maranian, Maya Ghoussaini, Shahana Ahmed, Caroline Baynes, Manjeet K Bolla, Qin Wang, Joe Dennis, Lesley McGuffog, Daniel Barrowdale, Andrew Lee, Sue Healey, Michael Lush, Daniel C Tessier, Daniel Vincent, Françis Bacot, , Ignace Vergote, Sandrina Lambrechts, Evelyn Despierre, Harvey A Risch, Anna González-Neira, Mary Anne Rossing, Guillermo Pita, Jennifer A Doherty, Nuria Alvarez, Melissa C Larson, Brooke L Fridley, Nils Schoof, Jenny Chang-Claude, Mine S Cicek, Julian Peto, Kimberly R Kalli, Annegien Broeks, Sebastian M Armasu, Marjanka K Schmidt, Linde M Braaf, Boris Winterhoff, Heli Nevanlinna, Gottfried E Konecny, Diether Lambrechts, Lisa Rogmann, Pascal Guénel, Attila Teoman, Roger L Milne, Joaquín J García, Angela Cox, Vijayalakshmi Shridhar, Barbara Burwinkel, Frederik Marme, Rebecca Hein, Elinor J Sawyer, Christopher A Haiman, Shan Wang-Gohrke, Irene L Andrulis, Kirsten B Moysich, John L Hopper, Kunle Odunsi, Annika Lindblom, Graham G Giles, Hermann Brenner, Jacques Simard, Galina Lurie, Peter A Fasching, Michael E Carney, Paolo Radice, Lynne R Wilkens, Anthony Swerdlow, Marc T Goodman, Hiltrud Brauch, Montserrat Garcia-Closas, Peter Hillemanns, Robert Winqvist, Matthias Dürst, Peter Devilee, Ingo Runnebaum, Anna Jakubowska, Jan Lubiński, Arto Mannermaa, Ralf Bützow, Natalia V Bogdanova, Thilo Dörk, Liisa M Pelttari, Wei Zheng, Arto Leminen, Hoda Anton-Culver, Clareann H Bunker, Vessela Kristensen, Roberta B Ness, Kenneth Muir, Robert Edwards, Alfons Meindl, Florian Heitz, Keitaro Matsuo, Andreas du Bois, Anna H Wu, Philipp Harter, Soo-Hwang Teo, Ira Schwaab, Xiao-Ou Shu, William Blot, Satoyo Hosono, Daehee Kang, Toru Nakanishi, Mikael Hartman, Yasushi Yatabe, Ute Hamann, Beth Y Karlan, Suleeporn Sangrajrang, Susanne Krüger Kjaer, Valerie Gaborieau, Allan Jensen, Diana Eccles, Estrid Høgdall, Chen-Yang Shen, Judith Brown, Yin Ling Woo, Mitul Shah, Mat Adenan Noor Azmi, Robert Luben, Siti Zawiah Omar, Kamila Czene, Robert A Vierkant, Børge G Nordestgaard, Henrik Flyger, Celine Vachon, Janet E Olson, Xianshu Wang, Douglas A Levine, Anja Rudolph, Rachel Palmieri Weber, Dieter Flesch-Janys, Edwin Iversen, Stefan Nickels, Joellen M Schildkraut, Isabel dos Santos Silva, Daniel W Cramer, Lorna Gibson, Kathryn L Terry, Olivia Fletcher, Allison F Vitonis, C Ellen van der Schoot, Elizabeth M Poole, Frans B L Hogervorst, Shelley S Tworoger, Jianjun Liu, Elisa V Bandera, Jingmei Li, Sara H Olson, Keith Humphreys, Irene Orlow, Carl Blomqvist, Lorna Rodriguez-Rodriguez, Kristiina Aittomäki, Helga B Salvesen, Taru A Muranen, Elisabeth Wik, Barbara Brouwers, Camilla Krakstad, Els Wauters, Mari K Halle, Hans Wildiers, Lambertus A Kiemeney, Claire Mulot, Katja K Aben, Pierre Laurent-Puig, Anne Mvan Altena, Thérèse Truong, Leon F A G Massuger, Javier Benitez, Tanja Pejovic, Jose Ignacio Arias Perez, Maureen Hoatlin, M Pilar Zamora, Linda S Cook, Sabapathy P Balasubramanian, Linda E Kelemen, Andreas Schneeweiss, Nhu D Le, Christof Sohn, Angela Brooks-Wilson, Ian Tomlinson, Michael J Kerin, Nicola Miller, Cezary Cybulski, Brian E Henderson, Janusz Menkiszak, Fredrick Schumacher, Nicolas Wentzensen, Loic Le Marchand, Hannah P Yang, Anna Marie Mulligan, Gord Glendon, Svend Aage Engelholm, Julia A Knight, Claus K Høgdall, Carmel Apicella, Martin Gore, Helen Tsimiklis, Honglin Song, Melissa C Southey, Agnes Jager, Ans M Wvan den Ouweland, Robert Brown, John W M Martens, James M Flanagan, Mieke Kriege, James Paul, Sara Margolin, Nadeem Siddiqui, Gianluca Severi, Alice S Whittemore, Laura Baglietto, Valerie McGuire, Christa Stegmaier, Weiva Sieh, Heiko Muller, Volker Arndt, France Labrèche, Yu-Tang Gao, Mark S Goldberg, Gong Yang, Martine Dumont, John R McLaughlin, Arndt Hartmann, Arif B Ekici, Matthias W Beckmann, Catherine M Phelan, Michael P Lux, Jenny Permuth-Wey, Bernard Peissel, Thomas A Sellers, Filomena Ficarazzi, Monica Barile, Argyrios Ziogas, Alan Ashworth, Aleksandra Gentry-Maharaj, Michael Jones, Susan J Ramus, Nick Orr, Usha Menon, Celeste L Pearce, Thomas Brüning, Malcolm C Pike, Yon-Dschun Ko, Jolanta Lissowska, Jonine Figueroa, Jolanta Kupryjanczyk, Stephen J Chanock, Agnieszka Dansonka-Mieszkowska, Arja Jukkola-Vuorinen, Iwona K Rzepecka, Katri Pylkäs, Mariusz Bidzinski, Saila Kauppila, Antoinette Hollestelle, Caroline Seynaeve, Rob A E M Tollenaar, Katarzyna Durda, Katarzyna Jaworska, Jaana M Hartikainen, Veli-Matti Kosma, Vesa Kataja, Natalia N Antonenkova, Jirong Long, Martha Shrubsole, Sandra Deming-Halverson, Artitaya Lophatananon, Pornthep Siriwanarangsan, Sarah Stewart-Brown, Nina Ditsch, Peter Lichtner, Rita K Schmutzler, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Chiu-Chen Tseng, Daniel O Stram, David Van Den Berg, Cheng Har Yip, M Kamran Ikram, Yew-Ching Teh, Hui Cai, Wei Lu, Lisa B Signorello, Qiuyin Cai, Dong-Young Noh, Keun-Young Yoo, Hui Miao, Philip Tsau-Choong Iau, Yik Ying Teo, James McKay, Charles Shapiro, Foluso Ademuyiwa, George Fountzilas, Chia-Ni Hsiung, Jyh-Cherng Yu, Ming-Feng Hou, Catherine S Healey, Craig Luccarini, Susan Peock, Dominique Stoppa-Lyonnet, Paolo Peterlongo, Timothy R Rebbeck, Marion Piedmonte, Christian F Singer, Eitan Friedman, Mads Thomassen, Kenneth Offit, Thomas V O Hansen, Susan L Neuhausen, Csilla I Szabo, Ignacio Blanco, Judy Garber, Steven A Narod, Jeffrey N Weitzel, Marco Montagna, Edith Olah, Andrew K Godwin, Drakoulis Yannoukakos, David E Goldgar, Trinidad Caldés, Evgeny N Imyanitov, Laima Tihomirova, Banu K Arun, Ian Campbell, Arjen R Mensenkamp, Christi J van Asperen, Kees E P van Roozendaal, Hanne Meijers-Heijboer, J Margriet Collée, Jan C Oosterwijk, Maartje J Hooning, Matti A Rookus, Rob B van der Luijt, Theo A Mvan Os, D Gareth Evans, Debra Frost, Elena Fineberg, Julian Barwell, Lisa Walker, M John Kennedy, Radka Platte, Rosemarie Davidson, Steve D Ellis, Trevor Cole, Brigitte Bressac-de Paillerets, Bruno Buecher, Francesca Damiola, Laurence Faivre, Marc Frénay, Olga M Sinilnikova, Olivier Caron, Sophie Giraud, Sylvie Mazoyer, Valérie Bonadona, Virginie Caux-Moncoutier, Aleksandra Toloczko-Grabarek, Jacek Gronwald, Tomasz Byrski, Amanda B Spurdle, Bernardo Bonanni, Daniela Zaffaroni, Giuseppe Giannini, Loris Bernard, Riccardo Dolcetti, Siranoush Manoukian, Norbert Arnold, Christoph Engel, Helmut Deissler, Kerstin Rhiem, Dieter Niederacher, Hansjoerg Plendl, Christian Sutter, Barbara Wappenschmidt, Ake Borg, Beatrice Melin, Johanna Rantala, Maria Soller, Katherine L Nathanson, Susan M Domchek, Gustavo C Rodriguez, Ritu Salani, Daphne Gschwantler Kaulich, Muy-Kheng Tea, Shani Shimon Paluch, Yael Laitman, Anne-Bine Skytte, Torben A Kruse, Uffe Birk Jensen, Mark Robson, Anne-Marie Gerdes, Bent Ejlertsen, Lenka Foretova, Sharon A Savage, Jenny Lester, Penny Soucy, Karoline B Kuchenbaecker, Curtis Olswold, Julie M Cunningham, Susan Slager, Vernon S Pankratz, Ed Dicks, Sunil R Lakhani, Fergus J Couch, Per Hall, Alvaro N A Monteiro, Simon A Gayther, Paul D P Pharoah, Roger R Reddel, Ellen L Goode, Mark H Greene, Douglas F Easton, Andrew Berchuck, Antonis C Antoniou, Georgia Chenevix-Trench, Alison M Dunning.
Nat. Genet.
PUBLISHED: 01-31-2013
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TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ?480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10(-12)) and BRCA1 mutation carrier (P = 1.6 × 10(-14)) breast and invasive ovarian (P = 1.3 × 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
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Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
Kyriaki Michailidou, Per Hall, Anna González-Neira, Maya Ghoussaini, Joe Dennis, Roger L Milne, Marjanka K Schmidt, Jenny Chang-Claude, Stig E Bojesen, Manjeet K Bolla, Qin Wang, Ed Dicks, Andrew Lee, Clare Turnbull, Nazneen Rahman, , Olivia Fletcher, Julian Peto, Lorna Gibson, Isabel Dos Santos Silva, Heli Nevanlinna, Taru A Muranen, Kristiina Aittomäki, Carl Blomqvist, Kamila Czene, Astrid Irwanto, Jianjun Liu, Quinten Waisfisz, Hanne Meijers-Heijboer, Muriel Adank, Rob B van der Luijt, Rebecca Hein, Norbert Dahmen, Lars Beckman, Alfons Meindl, Rita K Schmutzler, Bertram Müller-Myhsok, Peter Lichtner, John L Hopper, Melissa C Southey, Enes Makalic, Daniel F Schmidt, André G Uitterlinden, Albert Hofman, David J Hunter, Stephen J Chanock, Daniel Vincent, Francois Bacot, Daniel C Tessier, Sander Canisius, Lodewyk F A Wessels, Christopher A Haiman, Mitul Shah, Robert Luben, Judith Brown, Craig Luccarini, Nils Schoof, Keith Humphreys, Jingmei Li, Børge G Nordestgaard, Sune F Nielsen, Henrik Flyger, Fergus J Couch, Xianshu Wang, Celine Vachon, Kristen N Stevens, Diether Lambrechts, Matthieu Moisse, Robert Paridaens, Marie-Rose Christiaens, Anja Rudolph, Stefan Nickels, Dieter Flesch-Janys, Nichola Johnson, Zoe Aitken, Kirsimari Aaltonen, Tuomas Heikkinen, Annegien Broeks, Laura J Van't Veer, C Ellen van der Schoot, Pascal Guénel, Thérèse Truong, Pierre Laurent-Puig, Florence Menegaux, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, M Pilar Zamora, Jose Ignacio Arias Perez, Guillermo Pita, M Rosario Alonso, Angela Cox, Ian W Brock, Simon S Cross, Malcolm W R Reed, Elinor J Sawyer, Ian Tomlinson, Michael J Kerin, Nicola Miller, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Irene L Andrulis, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Annika Lindblom, Sara Margolin, Maartje J Hooning, Antoinette Hollestelle, Ans M W van den Ouweland, Agnes Jager, Quang M Bui, Jennifer Stone, Gillian S Dite, Carmel Apicella, Helen Tsimiklis, Graham G Giles, Gianluca Severi, Laura Baglietto, Peter A Fasching, Lothar Haeberle, Arif B Ekici, Matthias W Beckmann, Hermann Brenner, Heiko Muller, Volker Arndt, Christa Stegmaier, Anthony Swerdlow, Alan Ashworth, Nick Orr, Michael Jones, Jonine Figueroa, Jolanta Lissowska, Louise Brinton, Mark S Goldberg, France Labrèche, Martine Dumont, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Hiltrud Brauch, Ute Hamann, Thomas Brüning, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Bernardo Bonanni, Peter Devilee, Rob A E M Tollenaar, Caroline Seynaeve, Christi J van Asperen, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska, Katarzyna Durda, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Natalia V Bogdanova, Natalia N Antonenkova, Thilo Dörk, Vessela N Kristensen, Hoda Anton-Culver, Susan Slager, Amanda E Toland, Stephen Edge, Florentia Fostira, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Aiko Sueta, Anna H Wu, Chiu-Chen Tseng, David Van Den Berg, Daniel O Stram, Xiao-Ou Shu, Wei Lu, Yu-Tang Gao, Hui Cai, Soo Hwang Teo, Cheng Har Yip, Sze Yee Phuah, Belinda K Cornes, Mikael Hartman, Hui Miao, Wei Yen Lim, Jen-Hwei Sng, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Chen-Yang Shen, Chia-Ni Hsiung, Pei-Ei Wu, Shian-Ling Ding, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, William J Blot, Lisa B Signorello, Qiuyin Cai, Wei Zheng, Sandra Deming-Halverson, Martha Shrubsole, Jirong Long, Jacques Simard, Montse Garcia-Closas, Paul D P Pharoah, Georgia Chenevix-Trench, Alison M Dunning, Javier Benitez, Douglas F Easton.
Nat. Genet.
PUBLISHED: 01-30-2013
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Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ?9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility.
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Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.
PLoS ONE
PUBLISHED: 01-28-2013
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Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC) have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the "K2 Study", using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ?2 and false discovery rate <0.05) mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA) project and identified 60% (402) of the downregulated and 74% (469) of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.
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Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers.
Juliet D French, Maya Ghoussaini, Stacey L Edwards, Kerstin B Meyer, Kyriaki Michailidou, Shahana Ahmed, Sofia Khan, Mel J Maranian, Martin O'Reilly, Kristine M Hillman, Joshua A Betts, Thomas Carroll, Peter J Bailey, Ed Dicks, Jonathan Beesley, Jonathan Tyrer, Ana-Teresa Maia, Andrew Beck, Nicholas W Knoblauch, Constance Chen, Peter Kraft, Daniel Barnes, Anna González-Neira, M Rosario Alonso, Daniel Herrero, Daniel C Tessier, Daniel Vincent, Francois Bacot, Craig Luccarini, Caroline Baynes, Don Conroy, Joe Dennis, Manjeet K Bolla, Qin Wang, John L Hopper, Melissa C Southey, Marjanka K Schmidt, Annegien Broeks, Senno Verhoef, Sten Cornelissen, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Peter A Fasching, Christian R Loehberg, Arif B Ekici, Matthias W Beckmann, Julian Peto, Isabel Dos Santos Silva, Nichola Johnson, Zoe Aitken, Elinor J Sawyer, Ian Tomlinson, Michael J Kerin, Nicola Miller, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Thérèse Truong, Pierre Laurent-Puig, Florence Menegaux, Stig E Bojesen, Børge G Nordestgaard, Sune F Nielsen, Henrik Flyger, Roger L Milne, M Pilar Zamora, José Ignacio Arias Perez, Javier Benitez, Hoda Anton-Culver, Hermann Brenner, Heiko Muller, Volker Arndt, Christa Stegmaier, Alfons Meindl, Peter Lichtner, Rita K Schmutzler, Christoph Engel, Hiltrud Brauch, Ute Hamann, Christina Justenhoven, , Kirsimari Aaltonen, Päivi Heikkilä, Kristiina Aittomäki, Carl Blomqvist, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Aiko Sueta, Natalia V Bogdanova, Natalia N Antonenkova, Thilo Dörk, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Anna H Wu, Chiu-Chen Tseng, David Van Den Berg, Daniel O Stram, Diether Lambrechts, Stéphanie Peeters, Ann Smeets, Giuseppe Floris, Jenny Chang-Claude, Anja Rudolph, Stefan Nickels, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Bernardo Bonanni, Domenico Sardella, Fergus J Couch, Xianshu Wang, Vernon S Pankratz, Adam Lee, Graham G Giles, Gianluca Severi, Laura Baglietto, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Jacques Simard, Mark S Goldberg, France Labrèche, Martine Dumont, Soo Hwang Teo, Cheng Har Yip, Char-Hong Ng, Eranga Nishanthie Vithana, Vessela Kristensen, Wei Zheng, Sandra Deming-Halverson, Martha Shrubsole, Jirong Long, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L Andrulis, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Peter Devilee, Caroline Seynaeve, Montserrat Garcia-Closas, Jonine Figueroa, Stephen J Chanock, Jolanta Lissowska, Kamila Czene, Daniel Klevebring, Nils Schoof, Maartje J Hooning, John W M Martens, J Margriet Collée, Madeleine Tilanus-Linthorst, Per Hall, Jingmei Li, Jianjun Liu, Keith Humphreys, Xiao-Ou Shu, Wei Lu, Yu-Tang Gao, Hui Cai, Angela Cox, Sabapathy P Balasubramanian, William Blot, Lisa B Signorello, Qiuyin Cai, Paul D P Pharoah, Catherine S Healey, Mitul Shah, Karen A Pooley, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Mikael Hartman, Hui Miao, Jen-Hwei Sng, Xueling Sim, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Suleeporn Sangrajrang, Valerie Gaborieau, James McKay, Amanda E Toland, Christine B Ambrosone, Drakoulis Yannoukakos, Andrew K Godwin, Chen-Yang Shen, Chia-Ni Hsiung, Pei-Ei Wu, Shou-Tung Chen, Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk J Schoemaker, Bruce A J Ponder, Heli Nevanlinna, Melissa A Brown, Georgia Chenevix-Trench, Douglas F Easton, Alison M Dunning.
Am. J. Hum. Genet.
PUBLISHED: 01-03-2013
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Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.
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The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma.
Hum. Mol. Genet.
PUBLISHED: 11-23-2011
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In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10(-8), per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10(-14)) and rs12617313 (P = 7.48 × 10(-12)), both highly correlated with rs9679290 (r(2) > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r(2) < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10(-9), per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants.
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A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23.
Xifeng Wu, Ghislaine Scelo, Mark P Purdue, Nathaniel Rothman, Mattias Johansson, Yuanqing Ye, Zhaoming Wang, Diana Zelenika, Lee E Moore, Christopher G Wood, Egor Prokhortchouk, Valerie Gaborieau, Kevin B Jacobs, Wong-Ho Chow, Jorge R Toro, David Zaridze, Jie Lin, Jan Lubiński, Joanna Trubicka, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonóra Fabiánová, Dana Mates, Viorel Jinga, Vladimír Bencko, Alena Slamova, Ivana Holcatova, Marie Navratilova, Vladimir Janout, Paolo Boffetta, Joanne S Colt, Faith G Davis, Kendra L Schwartz, Rosamonde E Banks, Peter J Selby, Patricia Harnden, Christine D Berg, Ann W Hsing, Robert L Grubb, Heiner Boeing, Paolo Vineis, Francoise Clavel-Chapelon, Domenico Palli, Rosario Tumino, Vittorio Krogh, Salvatore Panico, Eric J Duell, José Ramón Quirós, Maria-Jose Sanchez, Carmen Navarro, Eva Ardanaz, Miren Dorronsoro, Kay-Tee Khaw, Naomi E Allen, H Bas Bueno-de-Mesquita, Petra H M Peeters, Dimitrios Trichopoulos, Jakob Linseisen, Börje Ljungberg, Kim Overvad, Anne Tjønneland, Isabelle Romieu, Elio Riboli, Victoria L Stevens, Michael J Thun, W Ryan Diver, Susan M Gapstur, Paul D Pharoah, Douglas F Easton, Demetrius Albanes, Jarmo Virtamo, Lars Vatten, Kristian Hveem, Tony Fletcher, Kvetoslava Koppova, Olivier Cussenot, Géraldine Cancel-Tassin, Simone Benhamou, Michelle A Hildebrandt, Xia Pu, Mario Foglio, Doris Lechner, Amy Hutchinson, Meredith Yeager, Joseph F Fraumeni, Mark Lathrop, Konstantin G Skryabin, James D McKay, Jian Gu, Paul Brennan, Stephen J Chanock.
Hum. Mol. Genet.
PUBLISHED: 10-18-2011
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Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D? = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10(-10) and P = 6.07 × 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.
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Genome-wide association study of HPV seropositivity.
Hum. Mol. Genet.
PUBLISHED: 09-06-2011
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High-risk ? mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas ? cutaneous HPV types (e.g. HPV8) have been implicated in non-melanoma skin cancer. Although antibodies against the capsid protein L1 of HPV are considered as markers of cumulative exposure, not all infected persons seroconvert. To identify common genetic variants that influence HPV seroconversion, we performed a two-stage genome-wide association study. Genome-wide genotyping of 316 015 single nucleotide polymorphisms was carried out using the Illumina HumanHap300 BeadChip in 4811 subjects from a central European case-control study of lung, head and neck and kidney cancer that had serology data available on 13 HPV types. Only one association met genome-wide significance criteria, namely that between HPV8 seropositivity and rs9357152 [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.24-1.50 for the minor allele G; P=1.2 × 10(-10)], a common genetic variant (minor allele frequency=0.33) located within the major histocompatibility complex (MHC) II region at 6p21.32. This association was subsequently replicated in an independent set of 2344 subjects from a Latin American case-control study of head and neck cancer (OR=1.35, 95% CI=1.18-1.56, P=2.2 × 10(-5)), yielding P=1.3 × 10(-14) in the combined analysis (P-heterogeneity=0.87). No heterogeneity was noted by cancer status (controls/lung cancer cases/head and neck cancer cases/kidney cancer cases). This study provides a proof of principle that genetic variation plays a role in antibody reactivity to HPV infection.
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Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium.
Jonine D Figueroa, Montserrat Garcia-Closas, Manjeet Humphreys, Radka Platte, John L Hopper, Melissa C Southey, Carmel Apicella, Fleur Hammet, Marjanka K Schmidt, Annegien Broeks, Rob A E M Tollenaar, Laura J Van't Veer, Peter A Fasching, Matthias W Beckmann, Arif B Ekici, Reiner Strick, Julian Peto, Isabel Dos Santos Silva, Olivia Fletcher, Nichola Johnson, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Barbara Burwinkel, Federik Marme, Andreas Schneeweiss, Christof Sohn, Stig Bojesen, Henrik Flyger, Børge G Nordestgaard, Javier Benitez, Roger L Milne, Jose Ignacio Arias, M Pilar Zamora, Hermann Brenner, Heiko Muller, Volker Arndt, Nazneen Rahman, Clare Turnbull, Sheila Seal, Anthony Renwick, Hiltrud Brauch, Christina Justenhoven, Thomas Brüning, , Jenny Chang-Claude, Rebecca Hein, Shan Wang-Gohrke, Thilo Dörk, Peter Schürmann, Michael Bremer, Peter Hillemanns, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Natalia Bogdanova, Natalia Antonenkova, Yuri I Rogov, Johann Hinrich Karstens, Marina Bermisheva, Darya Prokofieva, Shamil Hanafievich Gantcev, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Georgia Chenevix-Trench, Jonathan Beesley, Xiaoqing Chen, Arto Mannermaa, Veli-Matti Kosma, Ylermi Soini, Vesa Kataja, Diether Lambrechts, Betul T Yesilyurt, Marie-Rose Chrisiaens, Stéphanie Peeters, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Fergus Couch, Adam M Lee, Robert Diasio, Xianshu Wang, Graham G Giles, Gianluca Severi, Laura Baglietto, Catriona Maclean, Ken Offit, Mark Robson, Vijai Joseph, Mia Gaudet, Esther M John, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene Andrulis, Julia A Knight, Anna Marie Mulligan, Frances P O'Malley, Louise A Brinton, Mark E Sherman, Jolanta Lissowska, Stephen J Chanock, Maartje Hooning, John W M Martens, Ans M W van den Ouweland, J Margriet Collée, Per Hall, Kamila Czene, Angela Cox, Ian W Brock, Malcolm W R Reed, Simon S Cross, Paul Pharoah, Alison M Dunning, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska, Katarzyna Durda, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Chen-Yang Shen, Shian-Ling Ding, Huan-Ming Hsu, Jyh-Cherng Yu, Hoda Anton-Culver, Argyrios Ziogas, Alan Ashworth, Anthony Swerdlow, Michael Jones, Nick Orr, Amy Trentham-Dietz, Kathleen Egan, Polly Newcomb, Linda Titus-Ernstoff, Doug Easton, Amanda B Spurdle.
Hum. Mol. Genet.
PUBLISHED: 08-18-2011
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A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r(2)= 0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI = 1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI = 0.98-1.07, case-only P-heterogeneity = 7.6 × 10(-5)]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P= 6.7 × 10(-3)) and lobular histology (case-only P= 0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer.
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Extended telephone-based continuing care for alcohol dependence: 24-month outcomes and subgroup analyses.
Addiction
PUBLISHED: 08-08-2011
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To determine whether 18 months of telephone continuing care improves 24-month outcomes for patients with alcohol dependence. Subgroup analyses were performed to identify patients who would benefit most from continuing care.
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Confirmation of 5p12 as a susceptibility locus for progesterone-receptor-positive, lower grade breast cancer.
Roger L Milne, Ellen L Goode, Montserrat Garcia-Closas, Fergus J Couch, Gianluca Severi, Rebecca Hein, Zachary Fredericksen, Nuria Malats, M Pilar Zamora, José Ignacio Arias Perez, Javier Benitez, Thilo Dörk, Peter Schürmann, Johann H Karstens, Peter Hillemanns, Angela Cox, Ian W Brock, Graeme Elliot, Simon S Cross, Sheila Seal, Clare Turnbull, Anthony Renwick, Nazneen Rahman, Chen-Yang Shen, Jyh-Cherng Yu, Chiun-Sheng Huang, Ming-Feng Hou, Børge G Nordestgaard, Stig E Bojesen, Charlotte Lanng, Grethe Grenaker Alnæs, Vessela Kristensen, Anne-Lise Børrensen-Dale, John L Hopper, Gillian S Dite, Carmel Apicella, Melissa C Southey, Diether Lambrechts, Betul T Yesilyurt, Giuseppe Floris, Karin Leunen, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Jenny Chang-Claude, Shan Wang-Gohrke, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Graham G Giles, Laura Baglietto, Esther M John, Alexander Miron, Stephen J Chanock, Jolanta Lissowska, Mark E Sherman, Jonine D Figueroa, Natalia V Bogdanova, Natalia N Antonenkova, Iosif V Zalutsky, Yuri I Rogov, Peter A Fasching, Christian M Bayer, Arif B Ekici, Matthias W Beckmann, Hermann Brenner, Heiko Muller, Volker Arndt, Christa Stegmaier, Irene L Andrulis, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Alfons Meindl, Joerg Heil, Claus R Bartram, Rita K Schmutzler, Gilles D Thomas, Robert N Hoover, Olivia Fletcher, Lorna J Gibson, Isabel Dos Santos Silva, Julian Peto, Stefan Nickels, Dieter Flesch-Janys, Hoda Anton-Culver, Argyrios Ziogas, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, Marjanka K Schmidt, Annegien Broeks, Laura J van 't Veer, Rob A E M Tollenaar, Paul D P Pharoah, Alison M Dunning, Karen A Pooley, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Anna Jakubowska, Jan Lubiński, Katarzyna Jaworska, Katarzyna Durda, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, David J Hunter, Susan E Hankinson, Peter Kraft, Sara Lindstrom, Xiaoqing Chen, Jonathan Beesley, Ute Hamann, Volker Harth, Christina Justenhoven, , Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Maartje Hooning, Antoinette Hollestelle, Rogier A Oldenburg, Madeleine Tilanus-Linthorst, Elza Khusnutdinova, Marina Bermisheva, Darya Prokofieva, Albina Farahtdinova, Janet E Olson, Xianshu Wang, Manjeet K Humphreys, Qin Wang, Georgia Chenevix-Trench, Douglas F Easton.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 07-27-2011
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The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium.
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Computerized continuing care support for alcohol and drug dependence: a preliminary analysis of usage and outcomes.
J Subst Abuse Treat
PUBLISHED: 07-01-2011
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The central aim of this administrative data analysis was to examine usage of a Web-based disease management program designed to provide continuing recovery support to patients discharged from residential drug and alcohol treatment. Tailored clinical content was delivered in a multimedia format over the course of 18 months posttreatment. The program also included access to a recovery coach across the 18 months. Consistent with other disease management programs, program usage decreased over time. A small subsample of patients accessed a large number of program modules in the year following treatment; these patients had significantly higher abstinence rates and consumed less alcohol than patients accessing few or no modules. Regression analyses revealed a significant relationship between the number of modules accessed and substance use outcomes in the year following treatment when controlling for motivation, self-efficacy, and pretreatment substance use. Limiting the analyses to only the more compliant patients did not reduce the magnitude of these effects. These preliminary results suggest that computerized support programs may be beneficial to patients recently treated for drug and alcohol issues. Methods to increase program engagement need additional study.
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Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population.
PLoS ONE
PUBLISHED: 06-20-2011
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Genetic factors associated with the risk of smoking related cancers have until recently remained elusive. Since the publication of a genome-wide association study (GWAS) on lung cancer new genetic loci have been identified that appear to be associated with disease risk. In this replication study we genotyped 14 single nucleotide polymorphisms (SNPs) located at the 5p12.3-p15.33, 6p21.3-p22.1, 6q23-q27 and 15q25.1 loci in 874 lung, 450 bladder, 418 laryngeal cancer cases and cancer-free controls, matched by year of birth and sex to the cases. Our results revealed that loci in the chromosome region 15q25.1 (rs16969968[A], rs8034191[G]) and 5p15 (rs402710[T]) are associated with lung cancer risk in the Polish population (smoking status adjusted OR = 1.45, 1.35, 0.77; p ? 0.0001, 0.0005, 0.002; 95%CI 1.23-1.72, 1.14-1.59, 0.66-0.91 respectively). None of the other regions analyzed herein were implicated in the risk of lung, bladder or laryngeal cancer. This study supports previous findings on lung cancer but fails to show association of SNPs located in 15q25.1 and 5p15 region with other smoking related cancers like bladder and laryngeal cancer.
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Implementation of evidence-based substance use disorder continuing care interventions.
Psychol Addict Behav
PUBLISHED: 03-30-2011
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Continuing care following initial substance use disorder treatment often is associated with improved treatment outcomes and evidence-based interventions (EBIs) have been developed in this area. However, rates of patient participation in continuing care treatment and mutual help groups (MHGs) are low and a large gap exists between the existing EBIs and actual clinical care. This paper uses the Consolidated Framework for Implementation Research (CFIR; Damschroder et al., 2009) to review the literature on continuing care treatment and monitoring, and mutual help-group promotion. Although existing research provides implications for implementing EBIs in continuing care, few direct implementation trials have been conducted. This literature indicates that EBIs in continuing care have been successfully modified for different settings, that they can be delivered using different modalities (e.g., individual, group, and telephone-based care), and that low cost options are available. Additionally, much is known about the differential effectiveness of continuing care with different populations that may guide treatment programs and providers in selecting the most effective interventions for their clients. One significant barrier to successful implementation of EBIs for continuing care is the lack of information about incentives for providing continuing care across what in the CFIR terminology is a programs outer setting (i.e., external economic, political, and social setting), and its inner setting (i.e., internal political, structural, and cultural contexts). Implications for implementation of EBIs in substance use disorder continuing care are discussed.
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A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 02-18-2011
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Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35).
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A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.
James D McKay, Thérèse Truong, Valerie Gaborieau, Amélie Chabrier, Shu-Chun Chuang, Graham Byrnes, David Zaridze, Oxana Shangina, Neonila Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonóra Fabiánová, Alexandru Bucur, Vladimír Bencko, Ivana Holcatova, Vladimir Janout, Lenka Foretova, Pagona Lagiou, Dimitrios Trichopoulos, Simone Benhamou, Christine Bouchardy, Wolfgang Ahrens, Franco Merletti, Lorenzo Richiardi, Renato Talamini, Luigi Barzan, Kristina Kjaerheim, Gary J Macfarlane, Tatiana V Macfarlane, Lorenzo Simonato, Cristina Canova, Antonio Agudo, Xavier Castellsague, Ray Lowry, David I Conway, Patricia A McKinney, Claire M Healy, Mary E Toner, Ariana Znaor, María Paula Curado, Sergio Koifman, Ana Menezes, Victor Wünsch-Filho, Jose Eluf Neto, Leticia Fernández Garrote, Stefania Boccia, Gabriella Cadoni, Dario Arzani, Andrew F Olshan, Mark C Weissler, William K Funkhouser, Jingchun Luo, Jan Lubiński, Joanna Trubicka, Marcin Lener, Dorota Oszutowska, Stephen M Schwartz, Chu Chen, Sherianne Fish, David R Doody, Joshua E Muscat, Philip Lazarus, Carla J Gallagher, Shen-Chih Chang, Zuo-Feng Zhang, Qingyi Wei, Erich M Sturgis, Li-E Wang, Silvia Franceschi, Rolando Herrero, Karl T Kelsey, Michael D McClean, Carmen J Marsit, Heather H Nelson, Marjorie Romkes, Shama Buch, Tomoko Nukui, Shilong Zhong, Martin Lacko, Johannes J Manni, Wilbert H M Peters, Rayjean J Hung, John Mclaughlin, Lars Vatten, Inger Njølstad, Gary E Goodman, John K Field, Triantafillos Liloglou, Paolo Vineis, Francoise Clavel-Chapelon, Domenico Palli, Rosario Tumino, Vittorio Krogh, Salvatore Panico, Carlos A González, J Ramon Quiros, Carmen Martínez, Carmen Navarro, Eva Ardanaz, Nerea Larranaga, Kay-Tee Khaw, Timothy Key, H Bas Bueno-de-Mesquita, Petra H M Peeters, Antonia Trichopoulou, Jakob Linseisen, Heiner Boeing, Göran Hallmans, Kim Overvad, Anne Tjønneland, Merethe Kumle, Elio Riboli, Kristjan Välk, Tõnu Vooder, Tõnu Voodern, Andres Metspalu, Diana Zelenika, Anne Boland, Marc Delepine, Mario Foglio, Doris Lechner, Hélène Blanché, Ivo G Gut, Pilar Galán, Simon Heath, Mia Hashibe, Richard B Hayes, Paolo Boffetta, Mark Lathrop, Paul Brennan.
PLoS Genet.
PUBLISHED: 02-11-2011
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Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ? 5 × 10??). Two novel variants were identified, a 4q21 variant (rs1494961, p?=?1×10??) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10??) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10??); rs1229984-ADH1B, p = 7 × 10??; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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Association of a novel functional promoter variant (rs2075533 C>T) in the apoptosis gene TNFSF8 with risk of lung cancer--a finding from Texas lung cancer genome-wide association study.
Carcinogenesis
PUBLISHED: 02-02-2011
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Published genome-wide association studies (GWASs) have identified few variants in the known biological pathways involved in lung cancer etiology. To mine the possibly hidden causal single nucleotide polymorphisms (SNPs), we explored all SNPs in the extrinsic apoptosis pathway from our published GWAS dataset for 1154 lung cancer cases and 1137 cancer-free controls. In an initial association analysis of 611 tagSNPs in 41 apoptosis-related genes, we identified only 10 tagSNPs associated with lung cancer risk with a P value<10(-2), including four tagSNPs in DAPK1 and three tagSNPs in TNFSF8. Unlike DAPK1 SNPs, TNFSF8 rs2181033 tagged other four predicted functional but untyped SNPs (rs776576, rs776577, rs31813148 and rs2075533) in the promoter region. Therefore, we further tested binding affinity of these four SNPs by performing the electrophoretic mobility shift assay. We found that only rs2075533T allele modified levels of nuclear proteins bound to DNA, leading to significantly decreased expression of luciferase reporter constructs by 5- to -10-fold in H1299, HeLa and HCT116 cell lines compared with the C allele. We also performed a replication study of the untyped rs2075533 in an independent Texas population but did not confirm the protective effect. We further performed a mini meta-analysis for SNPs of TNFSF8 obtained from other four published lung cancer GWASs with 12 ?214 cases and 47? 721 controls, and we found that only rs3181366 (r2=0.69 with the untyped rs2075533) was associated to lung cancer risk (P=0.008). Our findings suggest a possible role of novel TNFSF8 variants in susceptibility to lung cancer.
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An analysis of single nucleotide polymorphisms of 125 DNA repair genes in the Texas genome-wide association study of lung cancer with a replication for the XRCC4 SNPs.
DNA Repair (Amst.)
PUBLISHED: 01-09-2011
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DNA repair genes are important for maintaining genomic stability and limiting carcinogenesis. We analyzed all single nucleotide polymorphisms (SNPs) of 125 DNA repair genes covered by the Illumina HumanHap300 (v1.1) BeadChips in a previously conducted genome-wide association study (GWAS) of 1154 lung cancer cases and 1137 controls and replicated the top-hits of XRCC4 SNPs in an independent set of 597 cases and 611 controls in Texas populations. We found that six of 20 XRCC4 SNPs were associated with a decreased risk of lung cancer with a P-value of 0.01 or lower in the discovery dataset, of which the most significant SNP was rs10040363 (P for allelic test=4.89 x 10??). Moreover, the data in this region allowed us to impute a potentially functional SNP rs2075685 (imputed P for allelic test=1.3 x 10?³). A luciferase reporter assay demonstrated that the rs2075685G>T change in the XRCC4 promoter increased expression of the gene. In the replication study of rs10040363, rs1478486, rs9293329, and rs2075685, however, only rs10040363 achieved a borderline association with a decreased risk of lung cancer in a dominant model (adjusted OR=0.80, 95% CI=0.62-1.03 and P=0.079). In the final combined analysis of both the Texas GWAS discovery and replication datasets, the strength of the association was increased for rs10040363 (adjusted OR=0.77, 95% CI=0.66-0.89, P(dominant)=5 x 10?? and P for trend=5 x 10??) and rs1478486 (adjusted OR=0.82, 95% CI=0.71-0.94, P(dominant)=6 x 10?³ and P for trend=3.5 x 10?³). Finally, we conducted a meta-analysis of these XRCC4 SNPs with available data from published GWA studies of lung cancer with a total of 12,312 cases and 47,921 controls, in which none of these XRCC4 SNPs was associated with lung cancer risk. It appeared that rs2075685, although associated with increased expression of a reporter gene and lung cancer risk in the Texas populations, did not have an effect on lung cancer risk in other populations. This study underscores the importance of replication using published data in larger populations.
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Treating alcoholism as a chronic disease: approaches to long-term continuing care.
Alcohol Res Health
PUBLISHED: 01-01-2011
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For many patients, alcohol and other drug (AOD) use disorders are chronic, recurring conditions involving multiple cycles of treatment, abstinence, and relapse. To disrupt this cycle, treatment can include continuing care to reduce the risk of relapse. The most commonly used treatment approach is initial intensive inpatient or outpatient care based on 12-step principles, followed by continuing care involving self-help groups, 12-step group counseling, or individual therapy. Although these programs can be effective, many patients drop out of initial treatment or do not complete continuing care. Thus, researchers and clinicians have begun to develop alternative approaches to enhance treatment retention in both initial and continuing care. One focus of these efforts has been the design of extended treatment models. These approaches increasingly blur the distinction between initial and continuing care and aim to prolong treatment participation by providing a continuum of care. Other researchers have focused on developing alternative treatment strategies (e.g., telephone-based interventions) that go beyond traditional settings and adaptive treatment algorithms that may improve outcomes for clients who do not respond well to traditional approaches.
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Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.
Xiaohong R Yang, Jenny Chang-Claude, Ellen L Goode, Fergus J Couch, Heli Nevanlinna, Roger L Milne, Mia Gaudet, Marjanka K Schmidt, Annegien Broeks, Angela Cox, Peter A Fasching, Rebecca Hein, Amanda B Spurdle, Fiona Blows, Kristy Driver, Dieter Flesch-Janys, Judith Heinz, Peter Sinn, Alina Vrieling, Tuomas Heikkinen, Kristiina Aittomäki, Päivi Heikkilä, Carl Blomqvist, Jolanta Lissowska, Beata Peplonska, Stephen Chanock, Jonine Figueroa, Louise Brinton, Per Hall, Kamila Czene, Keith Humphreys, Hatef Darabi, Jianjun Liu, Laura J van 't Veer, Flora E van Leeuwen, Irene L Andrulis, Gord Glendon, Julia A Knight, Anna Marie Mulligan, Frances P O'Malley, Nayana Weerasooriya, Esther M John, Matthias W Beckmann, Arndt Hartmann, Sebastian B Weihbrecht, David L Wachter, Sebastian M Jud, Christian R Loehberg, Laura Baglietto, Dallas R English, Graham G Giles, Catriona A McLean, Gianluca Severi, Diether Lambrechts, Thijs Vandorpe, Caroline Weltens, Robert Paridaens, Ann Smeets, Patrick Neven, Hans Wildiers, Xianshu Wang, Janet E Olson, Victoria Cafourek, Zachary Fredericksen, Matthew Kosel, Celine Vachon, Helen E Cramp, Daniel Connley, Simon S Cross, Sabapathy P Balasubramanian, Malcolm W R Reed, Thilo Dörk, Michael Bremer, Andreas Meyer, Johann H Karstens, Aysun Ay, Tjoung-Won Park-Simon, Peter Hillemanns, José Ignacio Arias Perez, Primitiva Menéndez Rodríguez, Pilar Zamora, Javier Benitez, Yon-Dschun Ko, Hans-Peter Fischer, Ute Hamann, Beate Pesch, Thomas Brüning, Christina Justenhoven, Hiltrud Brauch, Diana M Eccles, William J Tapper, Sue M Gerty, Elinor J Sawyer, Ian P Tomlinson, Angela Jones, Michael Kerin, Nicola Miller, Niall McInerney, Hoda Anton-Culver, Argyrios Ziogas, Chen-Yang Shen, Chia-Ni Hsiung, Pei-Ei Wu, Show-Lin Yang, Jyh-Cherng Yu, Shou-Tung Chen, Giu-Cheng Hsu, Christopher A Haiman, Brian E Henderson, Loic Le Marchand, Laurence N Kolonel, Annika Lindblom, Sara Margolin, Anna Jakubowska, Jan Lubiński, Tomasz Huzarski, Tomasz Byrski, Bohdan Górski, Jacek Gronwald, Maartje J Hooning, Antoinette Hollestelle, Ans M W van den Ouweland, Agnes Jager, Mieke Kriege, Madeleine M A Tilanus-Linthorst, Margriet Collée, Shan Wang-Gohrke, Katri Pylkäs, Arja Jukkola-Vuorinen, Kari Mononen, Mervi Grip, Pasi Hirvikoski, Robert Winqvist, Arto Mannermaa, Veli-Matti Kosma, Jaana Kauppinen, Vesa Kataja, Päivi Auvinen, Ylermi Soini, Reijo Sironen, Stig E Bojesen, David Dynnes Ørsted, Diljit Kaur-Knudsen, Henrik Flyger, Børge G Nordestgaard, Helene Holland, Georgia Chenevix-Trench, Siranoush Manoukian, Monica Barile, Paolo Radice, Susan E Hankinson, David J Hunter, Rulla Tamimi, Suleeporn Sangrajrang, Paul Brennan, James McKay, Fabrice Odefrey, Valerie Gaborieau, Peter Devilee, P E A Huijts, R A E M Tollenaar, C Seynaeve, Gillian S Dite, Carmel Apicella, John L Hopper, Fleur Hammet, Helen Tsimiklis, Letitia D Smith, Melissa C Southey, Manjeet K Humphreys, Douglas Easton, Paul Pharoah, Mark E Sherman, Montserrat Garcia-Closas.
J. Natl. Cancer Inst.
PUBLISHED: 12-29-2010
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Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.
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A randomized trial of extended telephone-based continuing care for alcohol dependence: within-treatment substance use outcomes.
J Consult Clin Psychol
PUBLISHED: 09-30-2010
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The study tested whether adding up to 18 months of telephone continuing care, either as monitoring and feedback (TM) or longer contacts that included counseling (TMC), to intensive outpatient programs (IOPs) improved outcomes for alcohol-dependent patients.
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Isolated melanoma metastasis to stomach with possible regressed primary lesion: the importance of pursuing solitary melanoma metastases.
N. Z. Med. J.
PUBLISHED: 09-02-2010
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This is a case of a 60-year-old man who presented with anaemia and was subsequently diagnosed with a solitary 5 cm malignant melanoma metastasis of the gastric fundus. No primary lesion was identified. After surgical resection he is alive at 5 years follow-up, adding weight to the notion that solitary melanoma metastases should be aggressively pursued, as long-term survival is possible.
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A qualitative case study examining intervention tailoring for minorities.
Am J Health Behav
PUBLISHED: 07-08-2010
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To explore issues of intervention tailoring for ethnic minorities based on information and experiences shared by researchers affiliated with the Health Maintenance Consortium (HMC).
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Intervention taxonomy (ITAX): describing essential features of interventions.
Am J Health Behav
PUBLISHED: 07-08-2010
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To identify key features of interventions that need to be considered in the design, execution, and reporting of interventions.
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Moderators of response to telephone continuing care for alcoholism.
Am J Health Behav
PUBLISHED: 07-08-2010
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To evaluate potential moderators of the effect of adding extended telephone monitoring (TM) and telephone monitoring and counseling (TMC) continuing care to treatment as usual (TAU) for alcoholism. Continuing care was predicted to be more effective for patients with severe substance-use histories, poor initial response to treatment, and other risk factors for relapse.
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Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium.
J. Natl. Cancer Inst.
PUBLISHED: 06-14-2010
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Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies.
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Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3.
Mark P Purdue, Mattias Johansson, Diana Zelenika, Jorge R Toro, Ghislaine Scelo, Lee E Moore, Egor Prokhortchouk, Xifeng Wu, Lambertus A Kiemeney, Valerie Gaborieau, Kevin B Jacobs, Wong-Ho Chow, David Zaridze, Vsevolod Matveev, Jan Lubiński, Joanna Trubicka, Neonila Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonóra Fabiánová, Alexandru Bucur, Vladimír Bencko, Lenka Foretova, Vladimir Janout, Paolo Boffetta, Joanne S Colt, Faith G Davis, Kendra L Schwartz, Rosamonde E Banks, Peter J Selby, Patricia Harnden, Christine D Berg, Ann W Hsing, Robert L Grubb, Heiner Boeing, Paolo Vineis, Francoise Clavel-Chapelon, Domenico Palli, Rosario Tumino, Vittorio Krogh, Salvatore Panico, Eric J Duell, José Ramón Quirós, Maria-Jose Sanchez, Carmen Navarro, Eva Ardanaz, Miren Dorronsoro, Kay-Tee Khaw, Naomi E Allen, H Bas Bueno-de-Mesquita, Petra H M Peeters, Dimitrios Trichopoulos, Jakob Linseisen, Börje Ljungberg, Kim Overvad, Anne Tjønneland, Isabelle Romieu, Elio Riboli, Anush Mukeria, Oxana Shangina, Victoria L Stevens, Michael J Thun, W Ryan Diver, Susan M Gapstur, Paul D Pharoah, Douglas F Easton, Demetrius Albanes, Stephanie J Weinstein, Jarmo Virtamo, Lars Vatten, Kristian Hveem, Inger Njølstad, Grethe S Tell, Camilla Stoltenberg, Rajiv Kumar, Kvetoslava Koppova, Olivier Cussenot, Simone Benhamou, Egbert Oosterwijk, Sita H Vermeulen, Katja K H Aben, Saskia L van der Marel, Yuanqing Ye, Christopher G Wood, Xia Pu, Alexander M Mazur, Eugenia S Boulygina, Nikolai N Chekanov, Mario Foglio, Doris Lechner, Ivo Gut, Simon Heath, Hélène Blanché, Amy Hutchinson, Gilles Thomas, Zhaoming Wang, Meredith Yeager, Joseph F Fraumeni, Konstantin G Skryabin, James D McKay, Nathaniel Rothman, Stephen J Chanock, Mark Lathrop, Paul Brennan.
Nat. Genet.
PUBLISHED: 05-03-2010
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We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10??) and rs7579899 (P = 2.3 × 10??), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10?¹?). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10??). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
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Voucher incentives increase treatment participation in telephone-based continuing care for cocaine dependence.
Drug Alcohol Depend
PUBLISHED: 04-19-2010
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Telephone-based monitoring is a promising approach to continuing care of substance use disorders, but patients often do not engage or participate enough to benefit. Voucher incentives can increase retention in outpatient treatment and continuing care, but may be less effective when reinforcement is delayed, as in telephone-based care. We compared treatment utilization rates among cocaine-dependent patients enrolled in telephone continuing care with and without voucher incentives to determine whether incentives increase participation in telephone-based care.
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The effect of alcohol treatment on social costs of alcohol dependence: results from the COMBINE study.
Med Care
PUBLISHED: 04-16-2010
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The COMBINE (combined pharmacotherapies and behavioral intervention) clinical trial recently evaluated the efficacy of pharmacotherapies, behavioral therapies, and their combinations for the treatment of alcohol dependence. Previously, the cost and cost-effectiveness of COMBINE have been studied. Policy makers, patients, and nonalcohol-dependent individuals may be concerned not only with alcohol treatment costs but also with the effect of alcohol interventions on broader social costs and outcomes.
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Revisiting the cost-effectiveness of the COMBINE study for alcohol dependent patients: the patient perspective.
Med Care
PUBLISHED: 04-01-2010
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Most cost and cost-effectiveness studies of substance abuse treatments focus on the costs to the provider/payer. Although this perspective is important, the costs incurred by patients should also be considered when evaluating treatment. This article presents estimates of patients costs associated with the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) alcohol treatments and evaluates the treatments cost-effectiveness from the patient perspective.
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Common genetic variation of insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-3, and acid labile subunit in relation to serum IGF-I levels and mammographic density.
Breast Cancer Res. Treat.
PUBLISHED: 01-28-2010
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Mammographic density is strongly related to increased breast cancer risk. Accumulating evidence indicates that a role for the IGF-pathway in mammographic density and breast cancer development. Here, we investigate whether common genetic variation in this pathway influences insulin-like growth factor-I (IGF-I) levels and mammographic density. In 1,916 premenopausal women within the Prospect-EPIC cohort, we examined associations of 14 haplotype tagging SNPs in the ALS, IGFBP1, and IGFBP3 genes with IGF-I circulating levels and mammographic density. In 657 women, who became postmenopausal during follow-up, we investigated how these SNPs were related with the decrease in density over menopause. Linear regression models were used for statistical analysis. None of the ALS or IGFBP3 SNPs were statistically significantly associated with IGF-I levels or mammographic density. The CC genotype for rs1908751 (IGFBP1) was associated with lower levels of IGF-I (110.9 ng/ml) compared to the CT/TT genotypes (115.7 ng/ml) (P = 0.04). Women with the CC genotype also had lower percent density, although not statistically significantly (P = 0.12). Women carrying the AA genotype for rs1995051 (IGFBP1) showed that borderline significantly lower IGF-I levels (P = 0.06) and significantly lower mammographic density (40.3% compared to 43.5% in the GG/GA genotypes; P = 0.05). No relationships were found for any of the SNPs in relation with changes in breast density over menopause. These findings suggest that common genetic variation in the IGFBP1 gene is weakly related to IGF-I levels and mammographic density. Our results do not provide support for such a role of genetic variants in the IGFBP3 and ALS genes.
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International Lung Cancer Consortium: coordinated association study of 10 potential lung cancer susceptibility variants.
Carcinogenesis
PUBLISHED: 01-27-2010
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Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3).
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Randomized trial of continuing care enhancements for cocaine-dependent patients following initial engagement.
J Consult Clin Psychol
PUBLISHED: 01-27-2010
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The effects of cognitive-behavioral relapse prevention (RP), contingency management (CM), and their combination (CM + RP) were evaluated in a randomized trial with 100 cocaine-dependent patients (58% female, 89% African American) who were engaged in treatment for at least 2 weeks and had an average of 44 days of abstinence at baseline.
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The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk.
BMC Cancer
PUBLISHED: 01-20-2010
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The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC).
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Does coordinated care management improve employment for substance-using welfare recipients?
J Stud Alcohol Drugs
PUBLISHED: 11-10-2009
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This study tested whether coordinated care management, a continuity of care intervention for substance-use disorders, improved employment among men and women on public assistance compared with usual welfare management.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.