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Find video protocols related to scientific articles indexed in Pubmed.
Epigenetic signatures of internal migration in Italy.
Int J Epidemiol
PUBLISHED: 10-15-2014
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Observational studies have suggested that the risks of non-communicable diseases in voluntary migrants become similar to those in the host population after one or more generations, supporting the hypothesis that these diseases have a predominantly environmental (rather than inherited) origin. However, no study has been conducted thus far to identify alterations at the molecular level that might mediate these changes in disease risk after migration.
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Dietary intake of acrylamide and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-11-2014
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Acrylamide, classified in 1994 by IARC as 'probably carcinogenic' to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results, and could not further examine histological subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) sub-cohort of women (n=325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method, and was evaluated both as a continuous variable (per 10µg/day) and in quintiles; when subgroups by histological EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 ?g/day. No associations, and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10µg/day:1.02, 95%CI:0.96-1.09; HRQ5vsQ1:0.97, 95%CI:0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.
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Prediagnostic immunoglobulin E levels and risk of chronic lymphocytic leukemia, other lymphomas and multiple myeloma-results of the European Prospective Investigation into Cancer and Nutrition.
Carcinogenesis
PUBLISHED: 09-30-2014
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Previous epidemiological studies suggest an inverse association between allergies, marked by elevated immunoglobulin (Ig) E levels, and non-Hodgkin lymphoma (NHL) risk. The evidence, however, is inconsistent and prospective data are sparse. We examined the association between prediagnostic total (low: <20; intermediate: 20-100; high >100 kU/l) and specific IgE (negative: <0.35; positive ?0.35 kU/I) concentrations against inhalant antigens and lymphoma risk in a study nested within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 1021 incident cases and matched controls of NHL, multiple myeloma (MM) and Hodgkin lymphoma with a mean follow-up time of 7 years were investigated. Multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CI) were calculated by conditional logistic regression. Specific IgE was not associated with the risk of MM, B-cell NHL and B-cell NHL subtypes. In contrast, total IgE levels were inversely associated with the risk of MM [high level: OR = 0.40 (95% CI = 0.21-0.79)] and B-cell NHL [intermediate level: OR = 0.68 (95% CI = 0.53-0.88); high level: OR = 0.62 (95% CI = 0.44-0.86)], largely on the basis of a strong inverse association with chronic lymphocytic leukemia [CLL; intermediate level: OR = 0.49 (95% CI = 0.30-0.80); high level: OR = 0.13 (95% CI = 0.05-0.35)] risk. The inverse relationship for CLL remained significant for those diagnosed 5 years after baseline. The findings of this large prospective study demonstrated significantly lower prediagnostic total IgE levels among CLL and MM cases compared with matched controls. This corresponds to the clinical immunodeficiency state often observed in CLL patients prior to diagnosis. No support for an inverse association between prediagnostic levels of specific IgE and NHL risk was found.
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Carbohydrate intake in the etiology of Crohn's disease and ulcerative colitis.
Inflamm. Bowel Dis.
PUBLISHED: 09-30-2014
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Diet may have a role in the etiology of inflammatory bowel disease. In previous studies, the associations between increased intakes of carbohydrates, sugar, starch, and inflammatory bowel disease are inconsistent. However, few prospective studies have investigated the associations between these macronutrients and incident Crohn's disease (CD) or ulcerative colitis (UC).
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Circulating 25-Hydroxyvitamin D3 in Relation to Renal Cell Carcinoma Incidence and Survival in the EPIC Cohort.
Am. J. Epidemiol.
PUBLISHED: 09-08-2014
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Normal renal function is essential for vitamin D metabolism, but it is unclear whether circulating vitamin D is associated with risk of renal cell carcinoma (RCC). We assessed whether 25-hydroxyvitamin D3 (25(OH)D3) was associated with risk of RCC and death after RCC diagnosis in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC recruited 385,747 participants with blood samples between 1992 and 2000. The current study included 560 RCC cases, 557 individually matched controls, and 553 additional controls. Circulating 25(OH)D3 was assessed by mass spectrometry. Conditional and unconditional logistic regression models were used to calculate odds ratios and 95% confidence intervals. Death after RCC diagnosis was assessed using Cox proportional hazards models and flexible parametric survival models. A doubling of 25(OH)D3 was associated with 28% lower odds of RCC after adjustment for season of and age at blood collection, sex, and country of recruitment (odds ratio = 0.72, 95% confidence interval: 0.60, 0.86; P = 0.0004). This estimate was attenuated somewhat after additional adjustment for smoking status at baseline, circulating cotinine, body mass index (weight (kg)/height (m)(2)), and alcohol intake (odds ratio = 0.82, 95% confidence interval: 0.68, 0.99; P = 0.038). There was also some indication that both low and high 25(OH)D3 levels were associated with higher risk of death from any cause among RCC cases.
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Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
J. Natl. Cancer Inst. Monographs
PUBLISHED: 09-01-2014
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Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.
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Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: A nested case-control study: Plasma micronutrients and pancreatic cancer risk.
Int. J. Cancer
PUBLISHED: 08-30-2014
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Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (?- and ?-carotene, lycopene, ?-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), ?- and ?-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma ?-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend?=?0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend?=?0.06) and ?-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend?=?0.08. For ?- and ?-carotene, lutein, sum of carotenoids and ?-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of ?-carotene, zeaxanthin and ?-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted.
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Fruit and vegetable intake and cause-specific mortality in the EPIC study.
Eur. J. Epidemiol.
PUBLISHED: 08-26-2014
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Consumption of fruits and vegetables is associated with a lower overall mortality. The aim of this study was to identify causes of death through which this association is established. More than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition study were included, of which 25,682 were reported deceased after 13 years of follow-up. Information on lifestyle, diet and vital status was collected through questionnaires and population registries. Hazard ratios (HR) with 95% confidence intervals (95% CI) for death from specific causes were calculated from Cox regression models, adjusted for potential confounders. Participants reporting consumption of more than 569 g/day of fruits and vegetables had lower risks of death from diseases of the circulatory (HR for upper fourth 0.85, 95% CI 0.77-0.93), respiratory (HR for upper fourth 0.73, 95% CI 0.59-0.91) and digestive system (HR for upper fourth 0.60, 95% CI 0.46-0.79) when compared with participants consuming less than 249 g/day. In contrast, a positive association with death from diseases of the nervous system was observed. Inverse associations were generally observed for vegetable, but not for fruit consumption. Associations were more pronounced for raw vegetable consumption, when compared with cooked vegetable consumption. Raw vegetable consumption was additionally inversely associated with death from neoplasms and mental and behavioral disorders. The lower risk of death associated with a higher consumption of fruits and vegetables may be derived from inverse associations with diseases of the circulatory, respiratory and digestive system, and may depend on the preparation of vegetables and lifestyle factors.
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Dietary fat intake and risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition.
Cancer Epidemiol
PUBLISHED: 08-22-2014
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There are inconsistent and limited data available to assess the relationship between fat intake and risk of epithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes in relation to risk of EOC and its major histologic subtypes in the European Prospective Investigation into Cancer and Nutrition which includes incident invasive (n=1095) and borderline (n=96) EOC. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariate models, we observed no association with consumption of total fat, animal or plant fat, saturated fat, cholesterol, monounsaturated fat, or fatty fish and risk of invasive EOC. There was, however, an increased risk of invasive EOC in the highest category of intake (Quartile 4 vs. Quartile 1) of polyunsaturated fat (HR=1.22, 95% CI=1.02-1.48, P(trend)=0.02). We did not observe heterogeneity in the risk associations in comparisons of serous and endometrioid histologic subtypes. This study does not support an etiological role for total fat intake in relation to EOC risk; however, based on observations of a positive association between intake of polyunsaturated fat and invasive EOC risk in the current and previous studies, this fat subtype warrants further investigation to determine its potential role in EOC development.
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Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 08-07-2014
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Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk; the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting.
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Cancer rehabilitation services: an Italian population-based cohort study.
Tumori
PUBLISHED: 07-31-2014
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In Italy more than 55% of cancer patients live for more than 5 years after diagnosis, sometimes with several cancer-related sequelae. For this reason rehabilitation must offer not only physical interventions but also psychological, clinical, social and nutritional support. The CAREMORE pilot study was designed to assess whether cancer registries could serve to collect information on rehabilitation services, to describe and quantify the services provided by the National Health Service, and to examine the allocation of rehabilitation services to cancer patients.
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Zhaoming Wang, Bin Zhu, Mingfeng Zhang, Hemang Parikh, Jinping Jia, Charles C Chung, Joshua N Sampson, Jason W Hoskins, Amy Hutchinson, Laurie Burdette, Abdisamad Ibrahim, Christopher Hautman, Preethi S Raj, Christian C Abnet, Andrew A Adjei, Anders Ahlbom, Demetrius Albanes, Naomi E Allen, Christine B Ambrosone, Melinda Aldrich, Pilar Amiano, Christopher Amos, Ulrika Andersson, Gerald Andriole, Irene L Andrulis, Cecilia Arici, Alan A Arslan, Melissa A Austin, Dalsu Baris, Donald A Barkauskas, Bryan A Bassig, Laura E Beane Freeman, Christine D Berg, Sonja I Berndt, Pier Alberto Bertazzi, Richard B Biritwum, Amanda Black, William Blot, Heiner Boeing, Paolo Boffetta, Kelly Bolton, Marie-Christine Boutron-Ruault, Paige M Bracci, Paul Brennan, Louise A Brinton, Michelle Brotzman, H Bas Bueno-de-Mesquita, Julie E Buring, Mary Ann Butler, Qiuyin Cai, Géraldine Cancel-Tassin, Federico Canzian, Guangwen Cao, Neil E Caporaso, Alfredo Carrato, Tania Carreon, Angela Carta, Gee-Chen Chang, I-Shou Chang, Jenny Chang-Claude, Xu Che, Chien-Jen Chen, Chih-Yi Chen, Chung-Hsing Chen, Constance Chen, Kuan-Yu Chen, Yuh-Min Chen, Anand P Chokkalingam, Lisa W Chu, Francoise Clavel-Chapelon, Graham A Colditz, Joanne S Colt, David Conti, Michael B Cook, Victoria K Cortessis, E David Crawford, Olivier Cussenot, Faith G Davis, Immaculata De Vivo, Xiang Deng, Ti Ding, Colin P Dinney, Anna Luisa Di Stefano, W Ryan Diver, Eric J Duell, Joanne W Elena, Jin-Hu Fan, Heather Spencer Feigelson, Maria Feychting, Jonine D Figueroa, Adrienne M Flanagan, Joseph F Fraumeni, Neal D Freedman, Brooke L Fridley, Charles S Fuchs, Manuela Gago-Dominguez, Steven Gallinger, Yu-Tang Gao, Susan M Gapstur, Montserrat Garcia-Closas, Reina Garcia-Closas, Julie M Gastier-Foster, J Michael Gaziano, Daniela S Gerhard, Carol A Giffen, Graham G Giles, Elizabeth M Gillanders, Edward L Giovannucci, Michael Goggins, Nalan Gokgoz, Alisa M Goldstein, Carlos González, Richard Gorlick, Mark H Greene, Myron Gross, H Barton Grossman, Robert Grubb, Jian Gu, Peng Guan, Christopher A Haiman, Göran Hallmans, Susan E Hankinson, Curtis C Harris, Patricia Hartge, Claudia Hattinger, Richard B Hayes, Qincheng He, Lee Helman, Brian E Henderson, Roger Henriksson, Judith Hoffman-Bolton, Chancellor Hohensee, Elizabeth A Holly, Yun-Chul Hong, Robert N Hoover, H Dean Hosgood, Chin-Fu Hsiao, Ann W Hsing, Chao Agnes Hsiung, Nan Hu, Wei Hu, Zhibin Hu, Ming-Shyan Huang, David J Hunter, Peter D Inskip, Hidemi Ito, Eric J Jacobs, Kevin B Jacobs, Mazda Jenab, Bu-Tian Ji, Christoffer Johansen, Mattias Johansson, Alison Johnson, Rudolf Kaaks, Ashish M Kamat, Aruna Kamineni, Margaret Karagas, Chand Khanna, Kay-Tee Khaw, Christopher Kim, In-Sam Kim, Jin Hee Kim, Yeul Hong Kim, Young-Chul Kim, Young Tae Kim, Chang Hyun Kang, Yoo Jin Jung, Cari M Kitahara, Alison P Klein, Robert Klein, Manolis Kogevinas, Woon-Puay Koh, Takashi Kohno, Laurence N Kolonel, Charles Kooperberg, Christian P Kratz, Vittorio Krogh, Hideo Kunitoh, Robert C Kurtz, Nilgun Kurucu, Qing Lan, Mark Lathrop, Ching C Lau, Fernando Lecanda, Kyoung-Mu Lee, Maxwell P Lee, Loic Le Marchand, Seth P Lerner, Donghui Li, Linda M Liao, Wei-Yen Lim, Dongxin Lin, Jie Lin, Sara Lindstrom, Martha S Linet, Jolanta Lissowska, Jianjun Liu, Börje Ljungberg, Josep Lloreta, Daru Lu, Jing Ma, Nuria Malats, Satu Mannisto, Neyssa Marina, Giuseppe Mastrangelo, Keitaro Matsuo, Katherine A McGlynn, Roberta Mckean-Cowdin, Lorna H McNeill, Robert R McWilliams, Beatrice S Melin, Paul S Meltzer, James E Mensah, Xiaoping Miao, Dominique S Michaud, Alison M Mondul, Lee E Moore, Kenneth Muir, Shelley Niwa, Sara H Olson, Nick Orr, Salvatore Panico, Jae Yong Park, Alpa V Patel, Ana Patiño-García, Sofia Pavanello, Petra H M Peeters, Beata Peplonska, Ulrike Peters, Gloria M Petersen, Piero Picci, Malcolm C Pike, Stefano Porru, Jennifer Prescott, Xia Pu, Mark P Purdue, You-Lin Qiao, Preetha Rajaraman, Elio Riboli, Harvey A Risch, Rebecca J Rodabough, Nathaniel Rothman, Avima M Ruder, Jeong-Seon Ryu, Marc Sanson, Alan Schned, Fredrick R Schumacher, Ann G Schwartz, Kendra L Schwartz, Molly Schwenn, Katia Scotlandi, Adeline Seow, Consol Serra, Massimo Serra, Howard D Sesso, Gianluca Severi, Hongbing Shen, Min Shen, Sanjay Shete, Kouya Shiraishi, Xiao-Ou Shu, Afshan Siddiq, Luis Sierrasesúmaga, Sabina Sierri, Alan Dart Loon Sihoe, Debra T Silverman, Matthias Simon, Melissa C Southey, Logan Spector, Margaret Spitz, Meir Stampfer, Pär Stattin, Mariana C Stern, Victoria L Stevens, Rachael Z Stolzenberg-Solomon, Daniel O Stram, Sara S Strom, Wu-Chou Su, Malin Sund, Sook Whan Sung, Anthony Swerdlow, Wen Tan, Hideo Tanaka, Wei Tang, Ze-Zhang Tang, Adonina Tardón, Evelyn Tay, Philip R Taylor, Yao Tettey, David M Thomas, Roberto Tirabosco, Anne Tjonneland, Geoffrey S Tobias, Jorge R Toro, Ruth C Travis, Dimitrios Trichopoulos, Rebecca Troisi, Ann Truelove, Ying-Huang Tsai, Margaret A Tucker, Rosario Tumino, David Van Den Berg, Stephen K Van Den Eeden, Roel Vermeulen, Paolo Vineis, Kala Visvanathan, Ulla Vogel, Chaoyu Wang, Chengfeng Wang, Junwen Wang, Sophia S Wang, Elisabete Weiderpass, Stephanie J Weinstein, Nicolas Wentzensen, William Wheeler, Emily White, John K Wiencke, Alicja Wolk, Brian M Wolpin, Maria Pik Wong, Margaret Wrensch, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wu, Jay S Wunder, Yong-Bing Xiang, Jun Xu, Hannah P Yang, Pan-Chyr Yang, Yasushi Yatabe, Yuanqing Ye, Edward D Yeboah, Zhihua Yin, Chen Ying, Chong-Jen Yu, Kai Yu, Jian-Min Yuan, Krista A Zanetti, Anne Zeleniuch-Jacquotte, Wei Zheng, Baosen Zhou, Lisa Mirabello, Sharon A Savage, Peter Kraft, Stephen J Chanock, Meredith Yeager, Maria Terese Landi, Jianxin Shi, Nilanjan Chatterjee, Laufey T Amundadottir.
Hum. Mol. Genet.
PUBLISHED: 07-15-2014
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Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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Incidence of pleural mesothelioma in a community exposed to fibres with fluoro-edenitic composition in Biancavilla (Sicily, Italy).
Ann. Ist. Super. Sanita
PUBLISHED: 06-28-2014
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Amphibolic fibres with fluoro-edenitic composition characterize Biancavilla soil, including the major quarry from which building materials have been extensively extracted. These fibres induce mesothelioma in experimental animals and their in vitro biological action is similar to that of crocidolite.
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Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study.
BMC Med
PUBLISHED: 06-27-2014
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Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
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Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity.
Diabetes
PUBLISHED: 06-19-2014
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We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterize their association with intermediate phenotypes, and to investigate their role in type 2 diabetes (T2D) risk among normal-weight, overweight, and obese individuals. We investigated the association of genetic scores with euglycemic-hyperinsulinemic clamp- and oral glucose tolerance test-based measures of insulin resistance and secretion and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight, and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (? in SDs per allele [95% CI], -0.03 [-0.04, -0.01]; P = 0.004). This score was associated with lower BMI (-0.01 [-0.01, -0.0]; P = 0.02) and gluteofemoral fat mass (-0.03 [-0.05, -0.02; P = 1.4 × 10(-6)) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and ?-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (Pinteraction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (Pinteraction > 0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size.
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Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk: Results from the EPIC cohort study.
Int. J. Cancer
PUBLISHED: 06-17-2014
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Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee and tea consumption were assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found no significant association between overall gastric cancer risk and consumption of total coffee (HR 1.09, 95%-confidence intervals [CI]: 0.84-1.43; quartile 4 vs. non/quartile 1), caffeinated coffee (HR 1.14, 95%-CI: 0.82-1.59; quartile 4 vs. non/quartile 1), decaffeinated coffee (HR 1.07, 95%-CI: 0.75-1.53; tertile 3 vs. non/tertile 1) and tea (HR 0.81, 95%-CI: 0.59-1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100 mL/day (HR 1.06, 95%-CI: 1.03-1.11). Similarly, a significant positive association was observed between gastric cardia cancer risk and caffeinated coffee consumption (HR 1.98, 95%-CI: 1.16-3.36, p-trend=0.06; quartile 3 vs. non/quartile 1) and per increment of 100 mL/day (HR 1.09, 95%-CI: 1.04-1.14). In conclusion, consumption of total, caffeinated and decaffeinated coffee and tea is not associated with overall gastric cancer risk. However, total and caffeinated coffee consumption may be associated with an increased risk of gastric cardia cancer. Further prospective studies are needed to rule out chance or confounding.
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Mitochondrial DNA copy number and future risk of B-cell lymphoma in a nested case-control study in the prospective EPIC cohort.
Blood
PUBLISHED: 06-04-2014
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It has been suggested that mitochondrial dysfunction and DNA damage are involved in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a compensatory mechanism of mitochondrial dysfunction previously has been associated with B-cell lymphomas, in particular chronic lymphocytic leukemia (CLL). However, current evidence is limited and based on a relatively small number of cases. Using a nested case-control study, we extended these findings with a focus on subtype-specific analyses. Relative mtDNA copy number was measured in the buffy coat of prospectively collected blood of 469 lymphoma cases and 469 matched controls. The association between mtDNA copy number and the risk of developing lymphoma and histologic subtypes was examined using logistic regression models. We found no overall association between mtDNA and risk of lymphoma. Subtype analyses revealed significant increased risks of CLL (n = 102) with increasing mtDNA copy number (odds ratio = 1.34, 1.44, and 1.80 for quartiles 2-4, respectively; P trend = .001). mtDNA copy number was not associated with follow-up time, suggesting that this observation is not strongly influenced by indolent disease status. This study substantially strengthens the evidence that mtDNA copy number is related to risk of CLL and supports the importance of mitochondrial dysfunction as a possible mechanistic pathway in CLL ontogenesis.
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Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population.
Int. J. Cancer
PUBLISHED: 05-16-2014
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ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio?=?1.84, 95%CI?=?1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.
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Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: Multicentre, prospective cohort study.
Int. J. Cancer
PUBLISHED: 05-09-2014
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Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend?
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Survival after cancer in Italian persons with AIDS, 1986-2005: a population-based estimation.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-07-2014
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Cancer survival in persons with AIDS (PWA) after introduction of antiretroviral therapies remains poorly characterized. The aim is to provide population-based estimates of cancer survival, overall and for the most important cancer types in PWA, and a comparison with persons without AIDS (non-PWA) affected by the same cancer.
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Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.
PLoS Med.
PUBLISHED: 05-01-2014
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Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention.
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Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: The EPIC study.
Int. J. Cancer
PUBLISHED: 04-29-2014
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Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for ?5 vs. >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs. natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92) and duration of OC use (HR for ?9 vs. ?1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR?=?1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR?=?1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the etiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause.
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Meat and fish consumption and the risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition.
Int. J. Cancer
PUBLISHED: 04-17-2014
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Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 493,179 EPIC participants, recruited between 1992 and 2000. Until December 2008, 691 RCC cases have been identified. Meat and fish consumption was assessed at baseline using country-specific dietary assessment instruments; 24-hour recalls were applied in an 8% subsample for calibration purposes. Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Women with a high consumption of red meat (HR?=?1.36, 95% CI 1.14-1.62; calibrated, per 50 g/day) and processed meat (HR?=?1.78, 95% CI 1.05-3.03; calibrated, per 50 g/day) had a higher risk of RCC, while no association existed in men. For processed meat, the association with RCC incidence was prominent in premenopausal women and was lacking in postmenopausal women (p interaction?=?0.02). Neither poultry nor fish consumption were statistically significantly associated with the risk of RCC. The results show a distinct association of red and processed meat consumption with incident RCC in women but not in men. A biological explanation for these findings remains unclear.
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Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study.
Int. J. Cancer
PUBLISHED: 04-11-2014
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Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR?=?0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR?=?0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR?=?0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported.
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Dietary fat intake and development of specific breast cancer subtypes.
J. Natl. Cancer Inst.
PUBLISHED: 04-09-2014
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We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and saturated fat were associated with greater risk of ER(+)PR(+) disease (HR = 1.20, 95% confidence interval [CI] = 1.00 to 1.45; HR = 1.28, 95% CI = 1.09 to 1.52; highest vs lowest quintiles) but not ER(-)PR(-) disease. High saturated fat was statistically significantly associated with greater risk of HER2(-) disease. High saturated fat intake particularly increases risk of receptor-positive disease, suggesting saturated fat involvement in the etiology of this BC subtype.
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Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).
Eur. J. Epidemiol.
PUBLISHED: 04-04-2014
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A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.
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t(14;18) Translocation: A predictive blood biomarker for follicular lymphoma.
J. Clin. Oncol.
PUBLISHED: 03-31-2014
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The (14;18) translocation constitutes both a genetic hallmark and critical early event in the natural history of follicular lymphoma (FL). However, t(14;18) is also detectable in the blood of otherwise healthy persons, and its relationship with progression to disease remains unclear. Here we sought to determine whether t(14;18)-positive cells in healthy individuals represent tumor precursors and whether their detection could be used as an early predictor for FL.
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Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk.
Int. J. Cancer
PUBLISHED: 03-27-2014
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High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8-19%). Using the CRP-score as instrumental variable, genetically twofold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06-2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer.
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Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.
Int. J. Cancer
PUBLISHED: 03-17-2014
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The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer, but little is known about its association with stage and grade of the disease. The association between self-reported diabetes mellitus at recruitment and risk of prostate cancer was examined in the European Prospective Investigation into Cancer and Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate cancer over an average follow-up of 12 years. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by EPIC-participating center and age at recruitment, and adjusted for education, smoking status, body mass index, waist circumference, and physical activity. In a subset of men without prostate cancer, the cross-sectional association between circulating concentrations of androgens and insulin-like growth factor proteins with diabetes status was also investigated using linear regression models. Compared to men with no diabetes, men with diabetes had a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63-0.86). There was no evidence that the association differed by stage (p-heterogeneity, 0.19) or grade (p-heterogeneity, 0.48) of the disease, although the numbers were small in some disease subgroups. In a subset of 626 men with hormone measurements, circulating concentrations of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in men with diabetes compared to men without diabetes. This large European study has confirmed an inverse association between self-reported diabetes mellitus and subsequent risk of prostate cancer.
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Anthropometric measures and bladder cancer risk: A prospective study in the EPIC cohort.
Int. J. Cancer
PUBLISHED: 03-10-2014
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Anthropometric measures have been related to risk of several cancers. For bladder cancer, however, evidence is sparse. Comparability of existing studies is hampered by use of different obesity-measures, inadequate control for smoking, and few female cases. This study examined associations between height, weight, waist and hip circumference, waist-hip ratio, waist-height ratio, body mass index (BMI), recalled weight at age 20 and bladder cancer, and investigated effect modification by age, tumor aggressiveness and smoking. The study was conducted in the European Prospective Investigation into Cancer and Nutrition cohort, in 390,878 participants. Associations were calculated using Cox Proportional Hazards Models. During follow-up, 1,391 bladder cancers (1,018 male; 373 female) occurred. Height was unrelated to bladder cancer in both genders. We found a small but significant positive association with weight [1.04 (1.01-1.07) per 5 kilo], BMI [1.05 (1.02-1.08) per 2 units], waist circumference [1.04 (1.01-1.08) per 5 cm], waist-hip ratio (1.07 (1.02-1.13) per 0.05 unit] and waist-height ratio [1.07 (1.01-1.13) per 0.05 unit] in men. Stratification by smoking status confined associations in men to former smokers. In never smokers, we found no significant associations, suggesting residual confounding by smoking. Results did not differ with tumor aggressiveness and age. Residual analyses on BMI/waist circumference showed a significantly higher disease risk with BMI in men (p?=?0.01), but no association with waist circumference. In conclusion, in this large study, height was unrelated to bladder cancer, whereas overweight was associated with a slightly higher bladder cancer risk in men. This association may, however, be distorted by residual confounding by smoking.
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Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition.
Int. J. Cancer
PUBLISHED: 03-05-2014
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The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2?=?0.79, 95% confidence interval [CI]?=?[0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 ?=?1.99 [0.98-4.06]; high grade: ORlog2 ?=?0.75 [0.61-0.93], phet ???0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed.
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Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort.
Eur. J. Epidemiol.
PUBLISHED: 02-21-2014
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Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99 % confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046).
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Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition.
Int. J. Cancer
PUBLISHED: 02-06-2014
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Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (?- and ?-carotene, canthaxanthin, ?-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (?-, ?- and ?- and ?-tocopherol) and dietary consumption of ?-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile?=?0.63, 95% CI: 0.46, 0.87, p for trend?=?0.01), most notably proximal colon cancer (IRR for highest quartile?=?0.46, 95% CI: 0.27, 0.77, p for trend?=?0.01). Additionally, inverse associations for dietary ?-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties.
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A prospective study of one-carbon metabolism biomarkers and cancer of the head and neck and esophagus.
Int. J. Cancer
PUBLISHED: 01-29-2014
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Experimental and epidemiological data suggest that factors of one-carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre-diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post-diagnosis all-cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [ORQ4 vs. Q1 ] being 2.13 (95% confidence interval [95% CI] 1.13-4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (ORQ4 vs. Q1 0.63, 95% CI 0.35-1.16, p for trend 0.02). Subgroup analyses by anatomical sub-site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8 × 10(-4) ), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck.
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Prediagnostic telomere length and risk of B-cell lymphoma-Results from the EPIC cohort study.
Int. J. Cancer
PUBLISHED: 01-17-2014
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Recent epidemiological investigations have reported on the association between telomere length (TL) and a number of malignancies, including B-cell lymphoma (BCL). The reported results for BCLs are however inconsistent. We carried out a nested case-control study to determine whether TL is associated with future risk of BCL. Using quantitative polymerase chain reaction, the relative TL (i.e. the ratio of telomere repeat copy number to single gene copy number) was measured in mononuclear cell DNA of prediagnostic peripheral blood samples of 464 lymphoma cases and 464 matched controls (median time between blood collection and diagnosis, 4.6 years). Conditional logistic regression was used to analyze the association between TL and the risk of developing lymphoma and histologic subtypes. TL was significantly longer in cases compared to controls (p = 0.01). Multivariable models showed a significantly increased risk of BCL [odds ratio (OR) = 1.66, 1.80 and 3.20 for quartiles 2-4, respectively, p-trend = 0.001], diffuse large B-cell lymphoma (DLBCL) (OR = 1.20, 2.48 and 2.36 for quartiles 2-4, respectively, p-trend = 0.03) and follicular lymphoma (FL) (OR = 1.39, 1.90 and 2.69 for quartiles 2-4, respectively, p-trend = 0.02) with increasing TL. This study suggests an association between longer leucocyte TL and increased risk of BCL which was most pronounced for DLBCL and FL.
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Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study.
Int. J. Cancer
PUBLISHED: 01-13-2014
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Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3 : 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3 : 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.
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Dietary Intakes of Individual Flavanols and Flavonols Are Inversely Associated with Incident Type 2 Diabetes in European Populations.
J. Nutr.
PUBLISHED: 12-24-2013
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Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study was conducted in 8 European countries across 26 study centers with 340,234 participants contributing 3.99 million person-years of follow-up, among whom 12,403 incident T2D cases were ascertained and a center-stratified subcohort of 16,154 individuals was defined. We estimated flavonoid intake at baseline from validated dietary questionnaires using a database developed from Phenol-Explorer and USDA databases. We used country-specific Prentice-weighted Cox regression models and random-effects meta-analysis methods to estimate HRs. Among the flavanol subclass, we observed significant inverse trends between intakes of all individual flavan-3-ol monomers and risk of T2D in multivariable models (all P-trend < 0.05). We also observed significant trends for the intakes of proanthocyanidin dimers (HR for the highest vs. the lowest quintile: 0.81; 95% CI: 0.71, 0.92; P-trend = 0.003) and trimers (HR: 0.91; 95% CI: 0.80, 1.04; P-trend = 0.07) but not for proanthocyanidins with a greater polymerization degree. Among the flavonol subclass, myricetin (HR: 0.77; 95% CI: 0.64, 0.93; P-trend = 0.001) was associated with a lower incidence of T2D. This large and heterogeneous European study showed inverse associations between all individual flavan-3-ol monomers, proanthocyanidins with a low polymerization degree, and the flavonol myricetin and incident T2D. These results suggest that individual flavonoids have different roles in the etiology of T2D.
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Circulating biomarkers of tryptophan and the kynurenine pathway and lung cancer risk.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 12-19-2013
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Background: Imbalances in tryptophan metabolism have been linked to cancer related immune escape and implicated in several cancers, including lung cancer. Methods: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) that included 893 incident lung cancer cases and 1,748 matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk. Results: Tryptophan (Ptrend=2x10-5) and the kynurenine/tryptophan ratio (KTR) (Ptrend=4x10-5) were associated with lung cancer risk overall after adjusting for established risk factors. The odds ratios comparing the fifth and first quintiles (OR5thvs.1st) were 0.52 (95% CI: 0.37-0.74) for tryptophan and 1.74 (95% CI: 1.24-2.45) for KTR. After adjusting for plasma methionine (available from previous work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted Ptrend=0.13) and KTR (Ptrend=0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5thvs.1st being 2.83 (95% CI: 1.62-4.94, Ptrend=3x10-5) that was only marginally affected by adjusting for methionine. Conclusions: This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. While this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology. Impact: This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk.
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Type 1 plasminogen activator inhibitor as a common risk factor for cancer and ischaemic vascular disease: the EPICOR study.
BMJ Open
PUBLISHED: 11-16-2013
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We examined the association of plasminogen activator inhibitor-1 (PAI-1) levels with colorectal cancer, breast cancer, acute coronary syndrome (ACS) and ischaemic stroke.
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Estimates of cancer burden in Sicily.
Tumori
PUBLISHED: 10-26-2013
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Estimates are complementary epidemiological measures which allow to present data on cancer burden, especially in geographical areas where measurements of cancer occurrence are not supported by exhaustive statistics on incidence, mortality and survival. The aim of this paper is to provide cancer incidence, mortality and prevalence estimates and projections for the major cancers in the period 1970-2015 for the entire region of Sicily.
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The Association Between Dietary Flavonoid and Lignan Intakes and Incident Type 2 Diabetes in European Populations: The EPIC-InterAct study.
Diabetes Care
PUBLISHED: 10-15-2013
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OBJECTIVE To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations. RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis. RESULTS In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77-1.04]; P value trend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72-1.07]; P value trend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69-0.95]; P value trend = 0.020) and flavanols (HR 0.82 [95% CI 0.68-0.99]; P value trend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57-0.93]; P value trend = 0.029), were associated with a significantly reduced hazard of diabetes. CONCLUSIONS Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.
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N-acetyltransferase 2 phenotype, occupation, and bladder cancer risk: results from the EPIC cohort.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-03-2013
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An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case-control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition.
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Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status-Results from the EPIC cohort.
Int. J. Cancer
PUBLISHED: 07-12-2013
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Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1 ?=?1.56 (95% CI 1.15-2.13), ptrend ?=?0.02 for testosterone and ORQ4-Q1 ?=?1.33 (95% CI 0.99-1.79), ptrend ?=?0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1 ?=?1.32 (95% CI 0.87-2.01), ptrend ?=?0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1 ?=?0.94 (95% CI 0.60-1.47), ptrend ?=?0.34, phet ?=?0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen.
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Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status-A prospective study within the EPIC cohort.
Int. J. Cancer
PUBLISHED: 06-18-2013
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Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case-control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 ?=?1.41 [95% confidence interval (CI) 1.01-1.98] for the highest vs. lowest quartile; OR?=?1.17 [95% CI 1.04-1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend ?=?0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 ?=?1.38 [95% CI 1.01-1.89]; OR?=?1.19 [95% CI 1.04-1.36] per 1-SD increase in IGF-I, ptrend ?=?0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER- breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet ?=?0.03 for ER+/PR+ vs. ER-/PR- disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older.
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Relative and disease-free survival for breast cancer in relation to subtype: a population-based study.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 05-15-2013
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No population-based study has investigated breast cancer (BC) subtypes defined by including Ki67. The aim of this study was to evaluate the relative proportions of immunohistochemical subtypes and differences in relative and disease-free survival between subtypes, in relation to patient and other cancer characteristics in Italian BC patient.
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Lifestyle factors and mortality risk in individuals with diabetes mellitus: are the associations different from those in individuals without diabetes?
Diabetologia
PUBLISHED: 04-22-2013
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Thus far, it is unclear whether lifestyle recommendations for people with diabetes should be different from those for the general public. We investigated whether the associations between lifestyle factors and mortality risk differ between individuals with and without diabetes.
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Lifestyle, dietary factors, and antibody levels to oral bacteria in cancer-free participants of a European cohort study.
Cancer Causes Control
PUBLISHED: 03-20-2013
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Increasing evidence suggests that oral microbiota play a pivotal role in chronic diseases, in addition to the well-established role in periodontal disease. Moreover, recent studies suggest that oral bacteria may also be involved in carcinogenesis; periodontal disease has been linked to several cancers. In this study, we examined whether lifestyle factors have an impact on antibody levels to oral bacteria.
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Polymorphisms of Helicobacter pylori signaling pathway genes and gastric cancer risk in the European Prospective Investigation into Cancer-Eurgast cohort.
Int. J. Cancer
PUBLISHED: 02-28-2013
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Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. Single nucleotide polymorphisms (SNPs) in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1,284 matched controls from the European Prospective Investigation into Cancer cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model, we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p = 0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p = 0.0003) and CD14 with cardia GC (p = 0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results, we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC.
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High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.
Eur. J. Cancer
PUBLISHED: 02-27-2013
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We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008.
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Prediagnostic plasma testosterone, sex hormone-binding globulin, IGF-I and hepatocellular carcinoma: etiological factors or risk markers?
Int. J. Cancer
PUBLISHED: 02-11-2013
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Elevated prediagnostic testosterone and insulin-like growth factor I (IGF-I) concentrations have been proposed to increase risk of hepatocellular carcinoma (HCC). However, the metabolism of these hormones is altered as a consequence of liver damage and they may have clinical utility as HCC risk markers. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition cohort and included 125 incident HCC cases and 247 individually matched controls. Testosterone, sex hormone-binding globulin (SHBG) and IGF-I were analyzed by immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression. The area under the receiver operating curves (AUC) was calculated to assess HCC predictive ability of the tested models. After adjustments for epidemiological variables (body mass index, smoking, ethanol intake, hepatitis and diabetes) and liver damage (a score based on albumin, bilirubin, aspartate aminotransaminase, alanine aminotransaminase, gamma-glutamyltransferase and alkaline phosphatase concentrations), only SHBG remained significantly associated with risk [OR for top versus bottom tertile of 3.86 (1.32-11.3), p(trend) = 0.009]. As a single factor SHBG had an AUC of 0.81 (0.75-0.86). A small, but significant increase in AUC was observed when SHBG was added to a model including the liver damage score and epidemiological variables (from 0.89 to 0.91, p = 0.02) and a net reclassification of 0.47% (0.45-0.48). The observed associations of HCC with prediagnostic SHBG, free testosterone and IGF-I concentrations are in directions opposite to that expected under the etiological hypotheses. SHBG has a potential to be tested as prediagnostic risk marker for HCC.
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Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study.
Int. J. Cancer
PUBLISHED: 02-08-2013
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Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend ?=?0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend ?=?0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.
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Methylome analysis and epigenetic changes associated with menarcheal age.
PLoS ONE
PUBLISHED: 01-01-2013
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Reproductive factors have been linked to both breast cancer and DNA methylation, suggesting methylation as an important mechanism by which reproductive factors impact on disease risk. However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR:1.32, 95%CI:1.14-1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR12-14vs.?11 yrs:1.78, 95%CI:1.01-3.17 and OR?15vs.?11 yrs:4.59, 95%CI:2.04-10.33; P for trend<0.0001). However, average levels of global methylation as measured by the Illumina technology were not significantly associated with menarcheal age. In locus by locus comparative analyses, only one CpG site had significantly different methylation depending on the menarcheal age category examined, but this finding was not replicated by pyrosequencing in an independent data set. This study suggests a link between age at menarche and genome wide DNA methylation, and the difference in results between the two arrays suggests that repetitive element methylation has a role in the association. Epigenetic changes may be modulated by menarcheal age, or the association may be a mirror of other important changes in early life that have a detectable effect on both methylation levels and menarcheal age.
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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.