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Find video protocols related to scientific articles indexed in Pubmed.
Intrauterine devices and endometrial cancer risk: A pooled analysis of the Epidemiology of Endometrial Cancer Consortium.
Int. J. Cancer
PUBLISHED: 07-30-2014
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Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR?=?0.81, 95% CI?=?0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR?=?0.69, 95% CI?=?0.58-0.82), older age at first use (?35 years pooled-OR?=?0.53, 95% CI?=?0.43-0.67), older age at last use (?45 years pooled-OR?=?0.60, 95% CI?=?0.50-0.72), longer duration of use (?10 years pooled-OR?=?0.61, 95% CI?=?0.52-0.71) and recent use (within 1 year of study entry pooled-OR?=?0.39, 95% CI?=?0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes.
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Clinical utility of droplet digital PCR for human cytomegalovirus.
J. Clin. Microbiol.
PUBLISHED: 05-28-2014
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Human cytomegalovirus (CMV) has historically been the major infectious cause of morbidity and mortality among patients receiving hematopoietic cell or organ transplant. Standard care in a transplant setting involves frequent monitoring of CMV viral load over weeks to months to determine when antiviral treatment may be required. Quantitative PCR (qPCR) is the standard molecular diagnostic method for monitoring. Recently, digital PCR (dPCR) has shown promise in viral diagnostics, although current dPCR systems have lower throughput than qPCR systems. Here, we compare qPCR and droplet digital PCR (ddPCR) for CMV detection in patient plasma samples. Droplet digital PCR exhibits increased precision over qPCR at viral loads of ?4 log10 with equivalent sensitivity. However, retrospective analysis of longitudinal samples from transplant patients with CMV viral loads near therapeutic thresholds did not provide evidence that the improved precision of ddPCR would be of clinical benefit. Given the throughput advantages of current qPCR systems, a widespread switch to dPCR for CMV monitoring would appear premature.
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Occupational exposure and ovarian cancer risk.
Cancer Causes Control
PUBLISHED: 04-03-2014
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Relatively little work has been done concerning occupational risk factors in ovarian cancer. Although studies conducted in occupational settings have reported positive associations, their usefulness is generally limited by the lack of information on important confounders. In a population-based case-control study, we assessed risk for developing epithelial ovarian cancer (EOC) associated with occupational exposure while accounting for important confounders.
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Fatal breast cancer risk in relation to use of unopposed estrogen and combined hormone therapy.
Breast Cancer Res. Treat.
PUBLISHED: 03-09-2014
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Use of combined hormone therapy (CHT) is associated with increased breast cancer incidence, but it is unclear whether this translates into increased breast cancer mortality. To address this question, we conducted a population-based nested case-control study in Saskatchewan, Canada, where a population-based prescription drug database has existed since 1975. We evaluated fatal breast cancer risk in relation to recency and duration of use of CHT and unopposed estrogen hormone therapy (EHT). A total of 1,288 cases and 12,535 controls were included in the analyses. Exclusive use of EHT was not associated with fatal breast cancer risk, either overall or within categories of recency or duration [odds ratio (OR) for current vs. never use = 1.1; 95 % confidence interval (CI) 0.8-1.3]. Use of CHT (includes women who had also used EHT) was also not associated with fatal breast cancer risk (OR for current vs. never use = 0.9; 95 % CI 0.7-1.3), except for a suggestion of an increased risk with current long-term use. Consistent with prior studies, we observed no increased risk of fatal breast cancer associated with use of EHT. To date only a few studies have evaluated fatal breast cancer risk in relation to use of CHT, and collectively the results are inconsistent.
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Identification of chromosomally integrated human herpesvirus 6 by droplet digital PCR.
Clin. Chem.
PUBLISHED: 03-04-2014
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Human herpesvirus 6 (HHV-6) latently infects a majority of adults. In about 1% of the population HHV-6 exists in a chromosomally integrated form (ciHHV-6) that resides in every somatic and germ cell and can be transmitted through the germ line. Patients with ciHHV-6 have been misdiagnosed and unnecessarily treated for active HHV-6 infection, sometimes with important side effects, based on results from quantitative molecular HHV-6 tests.
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Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.
Linda E Kelemen, Kathryn L Terry, Marc T Goodman, Penelope M Webb, Elisa V Bandera, Valerie McGuire, Mary Anne Rossing, Qinggang Wang, Ed Dicks, Jonathan P Tyrer, Honglin Song, Jolanta Kupryjanczyk, Agnieszka Dansonka-Mieszkowska, Joanna Plisiecka-Halasa, Agnieszka Timorek, Usha Menon, Aleksandra Gentry-Maharaj, Simon A Gayther, Susan J Ramus, Steven A Narod, Harvey A Risch, John R McLaughlin, Nadeem Siddiqui, Rosalind Glasspool, James Paul, Karen Carty, Jacek Gronwald, Jan Lubiński, Anna Jakubowska, Cezary Cybulski, Lambertus A Kiemeney, Leon F A G Massuger, Anne M Van Altena, Katja K H Aben, Sara H Olson, Irene Orlow, Daniel W Cramer, Douglas A Levine, Maria Bisogna, Graham G Giles, Melissa C Southey, Fiona Bruinsma, Susanne K Kjaer, Estrid Høgdall, Allan Jensen, Claus K Høgdall, Lene Lundvall, Svend-Aage Engelholm, Florian Heitz, Andreas du Bois, Philipp Harter, Ira Schwaab, Ralf Bützow, Heli Nevanlinna, Liisa M Pelttari, Arto Leminen, Pamela J Thompson, Galina Lurie, Lynne R Wilkens, Diether Lambrechts, Els Van Nieuwenhuysen, Sandrina Lambrechts, Ignace Vergote, Jonathan Beesley, , Peter A Fasching, Matthias W Beckmann, Alexander Hein, Arif B Ekici, Jennifer A Doherty, Anna H Wu, Celeste L Pearce, Malcolm C Pike, Daniel Stram, Jenny Chang-Claude, Anja Rudolph, Thilo Dörk, Matthias Dürst, Peter Hillemanns, Ingo B Runnebaum, Natalia Bogdanova, Natalia Antonenkova, Kunle Odunsi, Robert P Edwards, Joseph L Kelley, Francesmary Modugno, Roberta B Ness, Beth Y Karlan, Christine Walsh, Jenny Lester, Sandra Orsulic, Brooke L Fridley, Robert A Vierkant, Julie M Cunningham, Xifeng Wu, Karen Lu, Dong Liang, Michelle A T Hildebrandt, Rachel Palmieri Weber, Edwin S Iversen, Shelley S Tworoger, Elizabeth M Poole, Helga B Salvesen, Camilla Krakstad, Line Bjorge, Ingvild L Tangen, Tanja Pejovic, Yukie Bean, Melissa Kellar, Nicolas Wentzensen, Louise A Brinton, Jolanta Lissowska, Montserrat Garcia-Closas, Ian G Campbell, Diana Eccles, Alice S Whittemore, Weiva Sieh, Joseph H Rothstein, Hoda Anton-Culver, Argyrios Ziogas, Catherine M Phelan, Kirsten B Moysich, Ellen L Goode, Joellen M Schildkraut, Andrew Berchuck, Paul D P Pharoah, Thomas A Sellers, Angela Brooks-Wilson, Linda S Cook, Nhu D Le.
Mol Nutr Food Res
PUBLISHED: 02-01-2014
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We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake.
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Exome-wide association study of endometrial cancer in a multiethnic population.
PLoS ONE
PUBLISHED: 01-01-2014
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Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.
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Hormone Contraception Before the First Birth and Endometrial Cancer Risk.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 12-10-2013
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There is a well-documented reduction in endometrial cancer (EC) risk with combined oral contraceptive (COC) use. COC use prior to the first full-term pregnancy may affect breast cancer risk for decades, but this relationship has not been investigated in EC. We investigated the risk for EC with COC use prior to the first full-term pregnancy. Cases (n=524) from a population-based cancer registry and age-matched controls (n=1032) were recruited between 2002 and 2006 in Alberta, Canada. Participants completed an in-person interview and provided detailed information on exogenous hormone use and other risk factors. Risk reductions in EC with COC use over the premenopausal years were consistent with the published literature. We also found evidence of a long-term, significant risk reduction in parous women with COC use prior to the first full-term pregnancy. Among parous women, ?5 years of COC use prior to a first full-term pregnancy was associated with a significant reduction in risk (adjusted OR=0.42, 95%CI=0.25-0.72), even if this exposure was a womans only use of COCs (adjusted OR=0.35, 95%CI=0.18-0.68). Further understanding of the long-term effects of COC use may help guide the timing of chemoprevention efforts via COCs.
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Risk of Ovarian Cancer and the NF-?B Pathway: Genetic association with IL1A and TNFSF10.
Bridget Charbonneau, Matthew S Block, William R Bamlet, Robert A Vierkant, Kimberly R Kalli, Zachary Fogarty, David N Rider, Thomas A Sellers, Shelley S Tworoger, Elizabeth Poole, Harvey A Risch, Helga B Salvesen, Lambertus A Kiemeney, Laura Baglietto, Graham G Giles, Gianluca Severi, Britton Trabert, Nicolas Wentzensen, Georgia Chenevix-Trench, , Alice S Whittemore, Weiva Sieh, Jenny Chang-Claude, Elisa V Bandera, Irene Orlow, Kathryn Terry, Marc T Goodman, Pamela J Thompson, Linda S Cook, Mary Anne Rossing, Roberta B Ness, Steven A Narod, Jolanta Kupryjanczyk, Karen Lu, Ralf Bützow, Thilo Dörk, Tanja Pejovic, Ian Campbell, Nhu D Le, Clareann H Bunker, Natalia Bogdanova, Ingo B Runnebaum, Diana Eccles, James Paul, Anna H Wu, Simon A Gayther, Estrid Hogdall, Florian Heitz, Stanley B Kaye, Beth Y Karlan, Hoda Anton-Culver, Jacek Gronwald, Claus K Hogdall, Diether Lambrechts, Peter A Fasching, Usha Menon, Joellen Schildkraut, Celeste Leigh Pearce, Douglas A Levine, Susanne Krüger Kjaer, Daniel Cramer, James M Flanagan, Catherine M Phelan, Robert Brown, Leon F A G Massuger, Honglin Song, Jennifer A Doherty, Camilla Krakstad, Dong Liang, Kunle Odunsi, Andrew Berchuck, Allan Jensen, Jan Lubiński, Heli Nevanlinna, Yukie T Bean, Galina Lurie, Argyrios Ziogas, Christine Walsh, Evelyn Despierre, Louise Brinton, Alexander Hein, Anja Rudolph, Agnieszka Dansonka-Mieszkowska, Sara H Olson, Philipp Harter, Jonathan Tyrer, Allison F Vitonis, Angela Brooks-Wilson, Katja K Aben, Malcolm C Pike, Susan J Ramus, Elisabeth Wik, Cezary Cybulski, Jie Lin, Lara Sucheston, Robert Edwards, Valerie McGuire, Jenny Lester, Andreas du Bois, Lene Lundvall, Shan Wang-Gohrke, Lukasz M Szafron, Sandrina Lambrechts, Hannah Yang, Matthias W Beckmann, Liisa M Pelttari, Anne M Van Altena, David Van Den Berg, Mari K Halle, Aleksandra Gentry-Maharaj, Ira Schwaab, Urmila Chandran, Janusz Menkiszak, Arif B Ekici, Lynne R Wilkens, Arto Leminen, Francesmary Modugno, Grace Friel, Joseph H Rothstein, Ignace Vergote, Montserrat Garcia-Closas, Michelle A T Hildebrandt, Piotr Sobiczewski, Linda E Kelemen, Paul D P Pharoah, Kirsten Moysich, Keith L Knutson, Julie M Cunningham, Brooke L Fridley, Ellen L Goode.
Cancer Res.
PUBLISHED: 11-22-2013
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A missense single nucleotide polymorphism in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561), but the functional implications of this polymorphism are undefined. IL-1? is regulated by and activated by NF-?B, a transcription factor family that induces transcription of IL1A along with other pro-inflammatory genes and is an important modifier in carcinogenesis. We therefore tagged SNPs in over 200 genes in the NF-?B pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell and 1,016 low grade serous (LGS), including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium (OCAC). In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer (OR=0.84, 95% CI: 0.76-0.93; p=0.00075), which remained intact even after excluding participants in the prior study (OR=0.85, 95% CI: 0.75-0.95; p=0.006). Considering a multiple-testing-corrected significance threshold of p< 2.5x10-5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential (LMP) tumors OR=0.85, 95% CI: 0.79-0.91; p=0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation related risk factors is warranted.
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Longitudinal changes in IGF-I and IGFBP-3, and mammographic density among postmenopausal women.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 09-09-2013
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A relation between the breast cancer risk factors, insulin-like growth factor-I (IGF-I) and mammographic density, is biologically plausible, but results from cross-sectional epidemiologic studies have been mixed. Our objective was to examine the relation in a longitudinal manner, that is, between the change in circulating IGF-I concentrations and the change in mammographic measures over one year. Data from an exercise intervention trial conducted in 302 postmenopausal women ages 50 to 74 years were used. Blood drawn at baseline and postintervention was assessed for IGF-I and its binding protein (IGFBP-3) by direct chemiluminscent immunoassay. Area and volumetric measurements of mammographic dense fibroglandular and nondense fatty tissue were made. Statistical analyses were based on multiple linear regression. A one SD (20.2 ng/mL) change in IGF-I over one year was associated with small changes in percent dense area [mean: 0.8%; 95% confidence interval (CI), 0.1-1.4] and dense area (mean: 1.2 cm(2); 95% CI, 0.2-2.1). Change in IGFBP-3 was also associated with percent and absolute dense area. Absolute and percent dense volume, and mammographic measures representing fatty tissue (nondense area and volume) were not associated with changes in IGF-I and IGFBP-3. Longitudinal associations may be more detectable than cross-sectional associations due to the absence of confounding by invariant personal factors. Absolute and percent dense area, measures that are related to breast cancer risk, may be affected by IGF-I. Confirmation should be sought in further longitudinal studies in which larger changes in the IGF system are evoked.
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Reliability of self-reported sun exposure in Canadian women and estimation of lifetime exposure to vitamin D from sun and diet.
Public Health Nutr
PUBLISHED: 07-25-2013
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To assess the inter-method reliability of the Ovarian Cancer in Alberta (OVAL) survey developed to estimate adult vitamin D exposure from sun and diet for every tenth year, against the longer Geraldton Skin Cancer Prevention Survey (the assumed gold standard). We also estimated total vitamin D exposure using the OVAL survey.
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Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA.
Madalene A Earp, Linda E Kelemen, Anthony M Magliocco, Kenneth D Swenerton, Georgia Chenevix-Trench, , Yi Lu, Alexander Hein, Arif B Ekici, Matthias W Beckmann, Peter A Fasching, Diether Lambrechts, Evelyn Despierre, Ignace Vergote, Sandrina Lambrechts, Jennifer A Doherty, Mary Anne Rossing, Jenny Chang-Claude, Anja Rudolph, Grace Friel, Kirsten B Moysich, Kunle Odunsi, Lara Sucheston-Campbell, Galina Lurie, Marc T Goodman, Michael E Carney, Pamela J Thompson, Ingo B Runnebaum, Matthias Dürst, Peter Hillemanns, Thilo Dörk, Natalia Antonenkova, Natalia Bogdanova, Arto Leminen, Heli Nevanlinna, Liisa M Pelttari, Ralf Bützow, Clareann H Bunker, Francesmary Modugno, Robert P Edwards, Roberta B Ness, Andreas du Bois, Florian Heitz, Ira Schwaab, Philipp Harter, Beth Y Karlan, Christine Walsh, Jenny Lester, Allan Jensen, Susanne K Kjær, Claus K Høgdall, Estrid Høgdall, Lene Lundvall, Thomas A Sellers, Brooke L Fridley, Ellen L Goode, Julie M Cunningham, Robert A Vierkant, Graham G Giles, Laura Baglietto, Gianluca Severi, Melissa C Southey, Dong Liang, Xifeng Wu, Karen Lu, Michelle A T Hildebrandt, Douglas A Levine, Maria Bisogna, Joellen M Schildkraut, Edwin S Iversen, Rachel Palmieri Weber, Andrew Berchuck, Daniel W Cramer, Kathryn L Terry, Elizabeth M Poole, Shelley S Tworoger, Elisa V Bandera, Urmila Chandran, Irene Orlow, Sara H Olson, Elisabeth Wik, Helga B Salvesen, Line Bjorge, Mari K Halle, Anne M Van Altena, Katja K H Aben, Lambertus A Kiemeney, Leon F A G Massuger, Tanja Pejovic, Yukie T Bean, Cezary Cybulski, Jacek Gronwald, Jan Lubiński, Nicolas Wentzensen, Louise A Brinton, Jolanta Lissowska, Montserrat Garcia-Closas, Ed Dicks, Joe Dennis, Douglas F Easton, Honglin Song, Jonathan P Tyrer, Paul D P Pharoah, Diana Eccles, Ian G Campbell, Alice S Whittemore, Valerie McGuire, Weiva Sieh, Joseph H Rothstein, James M Flanagan, James Paul, Robert Brown, Catherine M Phelan, Harvey A Risch, John R McLaughlin, Steven A Narod, Argyrios Ziogas, Hoda Anton-Culver, Aleksandra Gentry-Maharaj, Usha Menon, Simon A Gayther, Susan J Ramus, Anna H Wu, Celeste L Pearce, Malcolm C Pike, Agnieszka Dansonka-Mieszkowska, Iwona K Rzepecka, Lukasz M Szafron, Jolanta Kupryjanczyk, Linda S Cook, Nhu D Le, Angela Brooks-Wilson.
Hum. Genet.
PUBLISHED: 07-17-2013
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Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.
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Genome-wide association study of endometrial cancer in E2C2.
Hum. Genet.
PUBLISHED: 06-20-2013
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Endometrial cancer (EC), a neoplasm of the uterine epithelial lining, is the most common gynecological malignancy in developed countries and the fourth most common cancer among US women. Women with a family history of EC have an increased risk for the disease, suggesting that inherited genetic factors play a role. We conducted a two-stage genome-wide association study of Type I EC. Stage 1 included 5,472 women (2,695 cases and 2,777 controls) of European ancestry from seven studies. We selected independent single-nucleotide polymorphisms (SNPs) that displayed the most significant associations with EC in Stage 1 for replication among 17,948 women (4,382 cases and 13,566 controls) in a multiethnic population (African America, Asian, Latina, Hawaiian and European ancestry), from nine studies. Although no novel variants reached genome-wide significance, we replicated previously identified associations with genetic markers near the HNF1B locus. Our findings suggest that larger studies with specific tumor classification are necessary to identify novel genetic polymorphisms associated with EC susceptibility.
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Type I and II endometrial cancers: have they different risk factors?
J. Clin. Oncol.
PUBLISHED: 06-03-2013
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Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors.
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Case-control study of inflammatory markers and the risk of endometrial cancer.
Eur. J. Cancer Prev.
PUBLISHED: 05-25-2013
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Chronic inflammation may be important in endometrial cancer etiology. Several established endometrial cancer risk factors, particularly obesity, are hypothesized to operate through this pathway by increasing proinflammatory cytokines such as tumor necrosis factor ? (TNF-?), interleukin-6 (IL-6), and acute-phase protein C-reactive protein (CRP). This study sought to investigate the association between inflammatory markers and the risk of endometrial cancer (types I and II). We recruited 519 incident endometrial cancer cases and 964 frequency age-matched controls in this population-based case-control study in Alberta (Canada) from 2002 to 2006. Participants completed in-person interviews, were assessed for anthropometric measures, and provided 8-h fasting blood samples either preoperatively or postoperatively. Blood was analyzed for the concentrations of TNF-?, IL-6, and CRP by immunoassay. Endometrial cancer cases had consistently higher mean levels of TNF-?, IL-6, and CRP compared with controls in these predominantly postmenopausal women. After adjusting for age, all markers were associated with statistically significant increased risks for endometrial cancer; however, after multivariable adjustment, only the risk from CRP remained elevated (odds ratio=1.22, 95% confidence interval: 1.02-1.47). Similarly, upon stratification by cancer type, only CRP was associated positively with an increased risk for type I endometrial cancer (odds ratio=1.25, 95% confidence interval: 1.03-1.52). All markers were associated with an elevated risk for the more rare and aggressive type II cancers; however, these findings were statistically nonsignificant, likely because of the small number of cases in this group. In conclusion, we found epidemiologic evidence for an association between CRP and the risk of endometrial cancer, which was slightly stronger for type I cancer. No associations emerged for TNF-? and IL-6.
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Rapid detection of human cytomegalovirus UL97 and UL54 mutations directly from patient samples.
J. Clin. Microbiol.
PUBLISHED: 05-15-2013
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Human cytomegalovirus (CMV) is a significant contributor to morbidity and mortality in immunocompromised patients, particularly in the transplant setting. The availability of anti-CMV drugs has improved treatment, but drug resistance is an emerging problem. Here, we describe an improved, rapid, sequencing-based assay for the two genes in CMV where drug resistance occurs, the UL97 and UL54 genes. This assay is performed in 96-well format with a single master mix and provides clinical results within 2 days. It sequences codons 440 to 645 in the UL97 gene and codons 255 to 1028 in the UL54 gene with a limit of detection of 240 IU/ml. With this assay, we tested 43 specimens that had previously been tested for UL97 drug resistance and identified 3 with UL54 mutations. One of these patients had no concurrent UL97 mutation, pointing toward the need for an assay that facilitates dual UL97/UL54 gene testing for complete resistance profiling.
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Hormonal and reproductive risk factors for sporadic microsatellite stable and unstable endometrial tumors.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 05-15-2013
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Hormonal and reproductive factors modulate bioavailable estrogen to influence endometrial cancer risk. Estrogen affects the microsatellite status of tumors, but the relation between these estrogen-related factors and microsatellite instability (MSI) status of endometrial tumors is not known. We evaluated associations between hormonal and reproductive factors and risks of microsatellite stable (MSS) and MSI endometrial cancer among postmenopausal women (MSS cases = 258, MSI cases = 103, and controls = 742) in a population-based case-control study in Alberta, Canada (2002-2006). Polytomous logistic regression was used to estimate ORs and 95% confidence intervals (95% CI). We observed a significant trend in risk reduction for MSI (Ptrend = 0.005) but not MSS (Ptrend = 0.23) cancer with oral contraceptive use; with 5-year use or more, the risk reduction was stronger for MSI (OR = 0.42; 95% CI, 0.23-0.77) than for MSS cancer (OR = 0.80; 95% CI, 0.54-1.17; Pheterogeneity = 0.05). For more recent use (<30 years), the risk reduction was stronger for MSI (OR = 0.36; 95% CI, 0.19-0.69) than for MSS cancer (OR = 0.77; 95% CI, 0.51-1.15; Pheterogeneity = 0.032). No differential risk associations were observed for menopausal hormone use, parity and age at menarche, menopause or first pregnancy. We found limited evidence for statistical heterogeneity of associations of endometrial cancer risk with hormonal and reproductive factors by MSI status, except with oral contraceptive use. This finding suggests a potential role for the MMR system in the reduction of endometrial cancer risk associated with oral contraceptive use, although the exact mechanism is unclear. This study shows for the first time that oral contraceptive use is associated with a reduced risk for MSI but not for MSS endometrial cancer.
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Anthropometric measures and the risk of endometrial cancer, overall and by tumor microsatellite status and histological subtype.
Am. J. Epidemiol.
PUBLISHED: 05-14-2013
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Obesity is an established risk factor for endometrial cancer, but this association is not well understood for subtypes of endometrial cancer. We evaluated the association of recent and adult-life obesity with subtypes of endometrial cancer based on microsatellite status (microsatellite-stable (MSS) vs. microsatellite-instable (MSI)) and histology (type I vs. type II). Analyses were based on a population-based case-control study (524 cases and 1,032 controls) conducted in Alberta, Canada (2002-2006) and included the following groupings of subtypes: MSS = 337 and MSI = 130; type I = 458 and type II = 66. Logistic and polytomous logistic regression were used to estimate odds ratios and 95% confidence intervals for overall endometrial cancer and subtypes of endometrial cancer, respectively. The risks of all subtypes of endometrial cancer, except type II, increased with an increase in all of the anthropometric characteristics examined. The risks for MSI tumors were suggestively stronger than those for MSS tumors; the risk with high (?30) body mass index (weight (kg)/height (m)(2)) was significantly stronger for MSI tumors (odds ratio = 4.96, 95% confidence interval: 2.76, 8.91) than for MSS tumors (odds ratio = 2.33, 95% confidence interval: 1.66, 3.28) (P-heterogeneity = 0.02). Obesity is associated with most subtypes of endometrial cancer, and further studies are warranted to elucidate the biological mechanisms underlying the stronger risk for the MSI subtype with a high body mass index.
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Case-control study of lifetime alcohol consumption and endometrial cancer risk.
Cancer Causes Control
PUBLISHED: 05-08-2013
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Alcohol consumption is hypothesized to increase the risk of endometrial cancer by increasing circulating estrogen levels. This study sought to investigate the association between lifetime alcohol consumption and endometrial cancer risk.
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Inherited common variants in mitochondrial DNA and invasive serous epithelial ovarian cancer risk.
BMC Res Notes
PUBLISHED: 04-10-2013
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Mitochondria are the site of oxidative phosphorylation, a process which generates reactive oxygen species (ROS). Elevated ROS levels can lead to oxidative stress, a cellular state implicated in carcinogenesis. It is hypothesized that alternations in mitochondrial (MT) DNA, including heritable MT single nucleotide polymorphisms (MT-SNPs), have the potential to change the capacity of MT function, leading to increased oxidative stress and cancer risk. We investigated if common MT-SNPs and/or haplogroups and are associated with invasive serous ovarian cancer (OvCa) risk METHODS: A panel of 64 MT-SNPs designed to tag all common variation in the European MT genome (minor allele frequency (MAF) >1%, r^2 >0.8) was genotyped in study participants of European descent using the Sequenom MassARRAY iPlex Gold(R) system (Sequenom Inc, CA, USA). Invasive serous OvCa cases (n = 405) and frequency age-matched controls (n = 445) were drawn from a population-based case-control study of OvCa in western Canada. Binary logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (C.I.) for carriage of the minor versus major allele by case-control status. MitoTool was used to test the relationship between European haplogroup status and case-control status using Fishers exact test.
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Association between sex hormones, glucose homeostasis, adipokines, and inflammatory markers and mammographic density among postmenopausal women.
Breast Cancer Res. Treat.
PUBLISHED: 04-08-2013
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The biological mechanisms underlying the relationship between mammographic density and breast cancer risk are unknown. Our objective was to examine the association between mammographic density and circulating factors that are putative breast cancer intermediate endpoints. Biologic data from a year-long aerobic exercise intervention trial conducted in 302 postmenopausal women aged 50-74 years were analyzed. Sex hormones, markers of glucose homeostasis, inflammatory markers, and adipokines were assayed in fasting blood drawn at baseline and after 1 year. Area and volumetric measurements of mammographic dense fibroglandular and nondense fatty tissue were made. Multiple linear regression was used to examine the association between the circulating factors and mammographic measures and partial correlations were estimated. Mammographic nondense volume was positively correlated with concentrations of estradiol (r = 0.28), estrone (r = 0.13), insulin (r = 0.41), glucose (r = 0.15), leptin (r = 0.49), and C-reactive protein (r = 0.22), and negatively correlated with sex hormone binding globulin (r = -0.30) and adiponectin (r = -0.12) but correlations became null after adjustment for overall body adiposity as represented by body mass index and waist circumference. With adjustment for overall adiposity, mammographic dense volume, a measure that represents fibroglandular tissue, was negatively correlated with leptin (r = -0.19) and C-reactive protein (r = -0.19). As expected, circulating factors originating from or correlated with adipose tissue were also correlated with mammographic measures of breast adipose tissue, but not after adjustment for overall body adiposity. Interpreting correlations between adiposity-derived factors and mammographic measures whose validity may be affected by adiposity is problematic. To rectify this problem, future studies with very good measures of the volume of fibroglandular tissue in the breast will be necessary.
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Endometrial cancer and a family history of cancer.
Gynecol. Oncol.
PUBLISHED: 04-04-2013
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Lynch Syndrome (LS), an inherited genetic syndrome, predisposes to cancers such as colorectal and endometrial. However, the risk for endometrial cancer (EC) in women not affected by LS, but with a family history of cancer, is currently unknown. We examined the association between a family history of cancer and the risk for EC in non-LS patients.
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Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer.
Hui Shen, Brooke L Fridley, Honglin Song, Kate Lawrenson, Julie M Cunningham, Susan J Ramus, Mine S Cicek, Jonathan Tyrer, Douglas Stram, Melissa C Larson, Martin Köbel, , Argyrios Ziogas, Wei Zheng, Hannah P Yang, Anna H Wu, Eva L Wozniak, Yin Ling Woo, Boris Winterhoff, Elisabeth Wik, Alice S Whittemore, Nicolas Wentzensen, Rachel Palmieri Weber, Allison F Vitonis, Daniel Vincent, Robert A Vierkant, Ignace Vergote, David Van Den Berg, Anne M Van Altena, Shelley S Tworoger, Pamela J Thompson, Daniel C Tessier, Kathryn L Terry, Soo-Hwang Teo, Claire Templeman, Daniel O Stram, Melissa C Southey, Weiva Sieh, Nadeem Siddiqui, Yurii B Shvetsov, Xiao-Ou Shu, Viji Shridhar, Shan Wang-Gohrke, Gianluca Severi, Ira Schwaab, Helga B Salvesen, Iwona K Rzepecka, Ingo B Runnebaum, Mary Anne Rossing, Lorna Rodriguez-Rodriguez, Harvey A Risch, Stefan P Renner, Elizabeth M Poole, Malcolm C Pike, Catherine M Phelan, Liisa M Pelttari, Tanja Pejovic, James Paul, Irene Orlow, Siti Zawiah Omar, Sara H Olson, Kunle Odunsi, Stefan Nickels, Heli Nevanlinna, Roberta B Ness, Steven A Narod, Toru Nakanishi, Kirsten B Moysich, Alvaro N A Monteiro, Joanna Moes-Sosnowska, Francesmary Modugno, Usha Menon, John R McLaughlin, Valerie McGuire, Keitaro Matsuo, Noor Azmi Mat Adenan, Leon F A G Massuger, Galina Lurie, Lene Lundvall, Jan Lubiński, Jolanta Lissowska, Douglas A Levine, Arto Leminen, Alice W Lee, Nhu D Le, Sandrina Lambrechts, Diether Lambrechts, Jolanta Kupryjanczyk, Camilla Krakstad, Gottfried E Konecny, Susanne Krüger Kjaer, Lambertus A Kiemeney, Linda E Kelemen, Gary L Keeney, Beth Y Karlan, Rod Karevan, Kimberly R Kalli, Hiroaki Kajiyama, Bu-Tian Ji, Allan Jensen, Anna Jakubowska, Edwin Iversen, Satoyo Hosono, Claus K Høgdall, Estrid Høgdall, Maureen Hoatlin, Peter Hillemanns, Florian Heitz, Rebecca Hein, Philipp Harter, Mari K Halle, Per Hall, Jacek Gronwald, Martin Gore, Marc T Goodman, Graham G Giles, Aleksandra Gentry-Maharaj, Montserrat Garcia-Closas, James M Flanagan, Peter A Fasching, Arif B Ekici, Robert Edwards, Diana Eccles, Douglas F Easton, Matthias Dürst, Andreas du Bois, Thilo Dörk, Jennifer A Doherty, Evelyn Despierre, Agnieszka Dansonka-Mieszkowska, Cezary Cybulski, Daniel W Cramer, Linda S Cook, Xiaoqing Chen, Bridget Charbonneau, Jenny Chang-Claude, Ian Campbell, Ralf Bützow, Clareann H Bunker, Doerthe Brueggmann, Robert Brown, Angela Brooks-Wilson, Louise A Brinton, Natalia Bogdanova, Matthew S Block, Elizabeth Benjamin, Jonathan Beesley, Matthias W Beckmann, Elisa V Bandera, Laura Baglietto, Francois Bacot, Sebastian M Armasu, Natalia Antonenkova, Hoda Anton-Culver, Katja K Aben, Dong Liang, Xifeng Wu, Karen Lu, Michelle A T Hildebrandt, Joellen M Schildkraut, Thomas A Sellers, David Huntsman, Andrew Berchuck, Georgia Chenevix-Trench, Simon A Gayther, Paul D P Pharoah, Peter W Laird, Ellen L Goode, Celeste Leigh Pearce.
Nat Commun
PUBLISHED: 02-21-2013
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HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 × 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.
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Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.
Jennifer Permuth-Wey, Kate Lawrenson, Howard C Shen, Aneliya Velkova, Jonathan P Tyrer, Zhihua Chen, Hui-Yi Lin, Y Ann Chen, Ya-Yu Tsai, Xiaotao Qu, Susan J Ramus, Rod Karevan, Janet Lee, Nathan Lee, Melissa C Larson, Katja K Aben, Hoda Anton-Culver, Natalia Antonenkova, Antonis C Antoniou, Sebastian M Armasu, , Francois Bacot, Laura Baglietto, Elisa V Bandera, Jill Barnholtz-Sloan, Matthias W Beckmann, Michael J Birrer, Greg Bloom, Natalia Bogdanova, Louise A Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Bützow, Qiuyin Cai, Ian Campbell, Jenny Chang-Claude, Stephen Chanock, Georgia Chenevix-Trench, Jin Q Cheng, Mine S Cicek, Gerhard A Coetzee, Linda S Cook, Fergus J Couch, Daniel W Cramer, Julie M Cunningham, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer A Doherty, Thilo Dörk, Andreas du Bois, Matthias Dürst, Douglas F Easton, Diana Eccles, Robert Edwards, Arif B Ekici, Peter A Fasching, David A Fenstermacher, James M Flanagan, Montserrat Garcia-Closas, Aleksandra Gentry-Maharaj, Graham G Giles, Rosalind M Glasspool, Jesus Gonzalez-Bosquet, Marc T Goodman, Martin Gore, Bohdan Górski, Jacek Gronwald, Per Hall, Mari K Halle, Philipp Harter, Florian Heitz, Peter Hillemanns, Maureen Hoatlin, Claus K Høgdall, Estrid Høgdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Heather Jim, Kimberly R Kalli, Beth Y Karlan, Stanley B Kaye, Linda E Kelemen, Lambertus A Kiemeney, Fumitaka Kikkawa, Gottfried E Konecny, Camilla Krakstad, Susanne Krüger Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Johnathan M Lancaster, Nhu D Le, Arto Leminen, Douglas A Levine, Dong Liang, Boon Kiong Lim, Jie Lin, Jolanta Lissowska, Karen H Lu, Jan Lubiński, Galina Lurie, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R McLaughlin, Usha Menon, Francesmary Modugno, Kirsten B Moysich, Toru Nakanishi, Steven A Narod, Lotte Nedergaard, Roberta B Ness, Heli Nevanlinna, Stefan Nickels, Houtan Noushmehr, Kunle Odunsi, Sara H Olson, Irene Orlow, James Paul, Celeste L Pearce, Tanja Pejovic, Liisa M Pelttari, Malcolm C Pike, Elizabeth M Poole, Paola Raska, Stefan P Renner, Harvey A Risch, Lorna Rodriguez-Rodriguez, Mary Anne Rossing, Anja Rudolph, Ingo B Runnebaum, Iwona K Rzepecka, Helga B Salvesen, Ira Schwaab, Gianluca Severi, Viji Shridhar, Xiao-Ou Shu, Yurii B Shvetsov, Weiva Sieh, Honglin Song, Melissa C Southey, Beata Spiewankiewicz, Daniel Stram, Rebecca Sutphen, Soo-Hwang Teo, Kathryn L Terry, Daniel C Tessier, Pamela J Thompson, Shelley S Tworoger, Anne M Van Altena, Ignace Vergote, Robert A Vierkant, Daniel Vincent, Allison F Vitonis, Shan Wang-Gohrke, Rachel Palmieri Weber, Nicolas Wentzensen, Alice S Whittemore, Elisabeth Wik, Lynne R Wilkens, Boris Winterhoff, Yin Ling Woo, Anna H Wu, Yong-Bing Xiang, Hannah P Yang, Wei Zheng, Argyrios Ziogas, Famida Zulkifli, Catherine M Phelan, Edwin Iversen, Joellen M Schildkraut, Andrew Berchuck, Brooke L Fridley, Ellen L Goode, Paul D P Pharoah, Alvaro N A Monteiro, Thomas A Sellers, Simon A Gayther.
Nat Commun
PUBLISHED: 02-18-2013
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Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3 untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10(-8)) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10(-10)). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.
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Prevalence, clinical and virologic outcomes of hepatitis B virus co-infection in HIV-1 positive Kenyan women on antiretroviral therapy.
PLoS ONE
PUBLISHED: 02-13-2013
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Sub-Saharan Africa carries a high burden of co-infection with HIV-1 and hepatitis B virus (HBV). In this region, individuals with HIV-1/HBV co-infection on antiretroviral therapy (ART) frequently receive lamivudine as the only agent active against HBV, raising concerns for development of HBV resistance to lamivudine. We aimed to determine the prevalence, clinical, and virologic outcomes of chronic HBV infection, including HBV resistance to lamivudine, in a cohort of HIV-1 seropositive Kenyan women on long-term ART.
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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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GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.
Paul D P Pharoah, Ya-Yu Tsai, Susan J Ramus, Catherine M Phelan, Ellen L Goode, Kate Lawrenson, Melissa Buckley, Brooke L Fridley, Jonathan P Tyrer, Howard Shen, Rachel Weber, Rod Karevan, Melissa C Larson, Honglin Song, Daniel C Tessier, Francois Bacot, Daniel Vincent, Julie M Cunningham, Joe Dennis, Ed Dicks, , Katja K Aben, Hoda Anton-Culver, Natalia Antonenkova, Sebastian M Armasu, Laura Baglietto, Elisa V Bandera, Matthias W Beckmann, Michael J Birrer, Greg Bloom, Natalia Bogdanova, James D Brenton, Louise A Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Bützow, Ian Campbell, Michael E Carney, Renato S Carvalho, Jenny Chang-Claude, Y Anne Chen, Zhihua Chen, Wong-Ho Chow, Mine S Cicek, Gerhard Coetzee, Linda S Cook, Daniel W Cramer, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer A Doherty, Thilo Dörk, Andreas du Bois, Matthias Dürst, Diana Eccles, Robert Edwards, Arif B Ekici, Peter A Fasching, David Fenstermacher, James Flanagan, Yu-Tang Gao, Montserrat Garcia-Closas, Aleksandra Gentry-Maharaj, Graham Giles, Anxhela Gjyshi, Martin Gore, Jacek Gronwald, Qi Guo, Mari K Halle, Philipp Harter, Alexander Hein, Florian Heitz, Peter Hillemanns, Maureen Hoatlin, Estrid Høgdall, Claus K Høgdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Kimberly R Kalli, Beth Y Karlan, Linda E Kelemen, Lambertus A Kiemeney, Susanne Krüger Kjaer, Gottfried E Konecny, Camilla Krakstad, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu D Le, Nathan Lee, Janet Lee, Arto Leminen, Boon Kiong Lim, Jolanta Lissowska, Jan Lubiński, Lene Lundvall, Galina Lurie, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R McLaughlin, Usha Menon, Francesmary Modugno, Kirsten B Moysich, Toru Nakanishi, Steven A Narod, Roberta B Ness, Heli Nevanlinna, Stefan Nickels, Houtan Noushmehr, Kunle Odunsi, Sara Olson, Irene Orlow, James Paul, Tanja Pejovic, Liisa M Pelttari, Jenny Permuth-Wey, Malcolm C Pike, Elizabeth M Poole, Xiaotao Qu, Harvey A Risch, Lorna Rodriguez-Rodriguez, Mary Anne Rossing, Anja Rudolph, Ingo Runnebaum, Iwona K Rzepecka, Helga B Salvesen, Ira Schwaab, Gianluca Severi, Hui Shen, Vijayalakshmi Shridhar, Xiao-Ou Shu, Weiva Sieh, Melissa C Southey, Paul Spellman, Kazuo Tajima, Soo-Hwang Teo, Kathryn L Terry, Pamela J Thompson, Agnieszka Timorek, Shelley S Tworoger, Anne M Van Altena, David Van Den Berg, Ignace Vergote, Robert A Vierkant, Allison F Vitonis, Shan Wang-Gohrke, Nicolas Wentzensen, Alice S Whittemore, Elisabeth Wik, Boris Winterhoff, Yin Ling Woo, Anna H Wu, Hannah P Yang, Wei Zheng, Argyrios Ziogas, Famida Zulkifli, Marc T Goodman, Per Hall, Douglas F Easton, Celeste L Pearce, Andrew Berchuck, Georgia Chenevix-Trench, Edwin Iversen, Alvaro N A Monteiro, Simon A Gayther, Joellen M Schildkraut, Thomas A Sellers.
Nat. Genet.
PUBLISHED: 01-30-2013
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Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10(-9)) and 10p12 (rs1243180, P = 1.8 × 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.
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Carotid intima-media thickness determined vascular age and the Framingham Risk Score.
Crit Pathw Cardiol
PUBLISHED: 11-18-2011
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We examined carotid intima-media thickness (CIMT)-determined vascular age on the Framingham Risk Score (FRS) and the Framingham Heart Age in patients of diverse ethnic origin without a history of diabetes or established cardiovascular disease. In this cross-sectional study, 2291 men and women had CIMT obtained by high resolution B-mode ultrasound in a routine examination between August 1, 2000 and October 1, 2001. We randomly split the population into a training subset (n = 1114) and an analysis subset (n = 1177) using the training subset to regress the average CIMT for each individual on chronologic age. We compared the FRS using CIMT-determined vascular age versus chronologic age in the analysis subset. On average, CIMT-determined vascular age was less than chronologic age, which was less than FRS-heart age in all gender and ethnic groups. For estimated 10-year cardiovascular-disease risk among non-Hispanic whites, only 45.5% of male and 55.6% of female patients were concordant for both measures, and simple Kappa values were low (0.28 for males, 0.32 for females). Among non-Hispanic whites, 40.7% of males and 32.1% of females had greater risk using chronologic age rather than when using CIMT-determined vascular age. Conversely, 13.8% of males and 12.3% of females had a greater risk using CIMT-determined vascular age rather than when using chronologic age. A similar pattern was noted in the other ethnic groups. Our results suggest that CIMT may be very useful in improving risk discrimination in the FRS, and that substituting CIMT-determined vascular age may improve individual cardiovascular risk prediction.
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Case-control study of the metabolic syndrome and metabolic risk factors for endometrial cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 09-15-2011
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Metabolic syndrome may predict endometrial cancer risk better than diabetes, hypertension, dyslipidemia, dysglycemia, or weight alone, but few studies have examined this issue.
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Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers.
PLoS ONE
PUBLISHED: 08-12-2011
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Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC). We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP) within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity.
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Risk of endometrial cancer in relation to individual nutrients from diet and supplements.
Public Health Nutr
PUBLISHED: 07-14-2011
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Intake of nutrients may influence the risk of endometrial cancer (EC). We aimed to estimate the association of intake of individual nutrients from food and from food plus supplements with EC occurrence.
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Heparinized saline vs normal saline for maintenance of intravenous access in neonates: an evidence-based practice change.
Adv Neonatal Care
PUBLISHED: 07-07-2011
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To design, implement, and to evaluate the outcomes of an evidence-based practice change regarding the use of heparin in intravenous (IV) locks to improve patient safety. Phase I of the project examined dwell time, hours of patency, gestational age at birth and at time of IV lock insertion, birthweight and weight at time of insertion, and reason for discontinuation for IV access devices prior to and following the practice change from heparinized saline (HS) to normal saline (NS) flush. Phase II of the project was to determine the effect of the educational program on staff knowledge of the use of heparinized saline vs normal saline flushes.
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The role of psychiatric nurse faculty in establishing a campus suicide prevention program.
J Psychosoc Nurs Ment Health Serv
PUBLISHED: 06-12-2011
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Suicide among college students has received increased national attention over the past few decades, partly due to the publicity regarding high-profile suicide events on college campuses throughout the United States and its territories. Currently, suicide is identified as the second-leading cause of death in college students. Due to federal legislation such as the Garrett Lee Smith Memorial Act of 2004, many college campuses have been able to establish suicide prevention programs. This article describes how a psychiatric nurse faculty member successfully established a comprehensive suicide prevention program that was initially supported by grant funds from the Garrett Lee Smith Memorial Act.
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Case-control study of dietary patterns and endometrial cancer risk.
Nutr Cancer
PUBLISHED: 06-01-2011
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Dietary patterns, rather than intakes of specific foods or nutrients, may influence risk of endometrial cancer (EC). This population-based case-control study in Canada (2002-2006) included incident EC cases (n = 506) from the Alberta Cancer Registry and controls frequency age-matched to cases (n = 981). Past-year dietary patterns were defined using factor analysis of food frequency questionnaire data. Logistic regression was used to estimate EC risk within quartiles of dietary patterns. Three patterns (sweets, meat, plants) explained 23% of the variance in the dietary data. In multivariable models, EC risk was significantly reduced by 30% for women in the highest quartile of the healthier plants pattern (OR = 0.70, 95% CI 0.50-0.98, P trend = 0.02). When stratified by body mass index (BMI; kg/m(2)), risk was further reduced among overweight or obese women with a BMI ?25 (OR = 0.57, 95% CI 0.39-0.83; P trend = 0.004). EC was not associated with the less healthy sweets and meat patterns. However, risk was modestly, but not significantly, elevated for higher intakes of the meat pattern among overweight or obese women. A mostly plant-based dietary pattern may reduce EC risk. Recommendations for risk reduction should focus on maintaining a healthy weight and the role of diet should be studied further.
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Critical issues in the decision to retire: a comparison of retired and retirement-age faculty.
J Nurs Educ
PUBLISHED: 04-29-2011
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The nursing faculty workforce is on the verge of a crisis because the number of full-time faculty expected to retire in the next 10 years is predicted to escalate dramatically. To propose evidence-based strategies to retain qualified nursing faculty beyond retirement age, this study built on previous qualitative research. An initial phenomenological study of retirement-age faculty identified 15 critical issues in the decision to remain employed in academia. To determine the degree to which these factors are shared by retired and still-employed faculty and the relative importance of each of these factors, a quasi-experimental comparative study was conducted. A Likert scale questionnaire was administered to a convenience sample drawn from a national population using the snowball sampling technique. ANOVA established the difference between retired and still-working faculty; discriminant analysis identified eight predictor variables for faculty decisions to remain in academia.
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Stroke Recognition and Management.
Am J Nurs
PUBLISHED: 04-22-2011
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Early identification and treatment are the keys.
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Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium.
PLoS ONE
PUBLISHED: 04-12-2011
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Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (P(heterogeneity)?0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR?=?0.6 to 0.9; P(trend)?=?0.001 to 0.03). Results from replication set 2 were statistically homogeneous (P(heterogeneity)?0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs?=?1.2; P(trend)?0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (P(heterogeneity)?0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (P(interaction)?0.003), age at diagnosis (P(interaction)?=?0.04), and year of diagnosis (P(interaction)?=?0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required.
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The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing.
Paul D P Pharoah, Rachel T Palmieri, Susan J Ramus, Simon A Gayther, Irene L Andrulis, Hoda Anton-Culver, Natalia Antonenkova, Antonis C Antoniou, David Goldgar, , Mary S Beattie, Matthias W Beckmann, Michael J Birrer, Natalia Bogdanova, Kelly L Bolton, Wendy Brewster, Angela Brooks-Wilson, Robert Brown, Ralf Bützow, Trinidad Caldés, Maria Adelaide Caligo, Ian Campbell, Jenny Chang-Claude, Y Ann Chen, Linda S Cook, Fergus J Couch, Daniel W Cramer, Julie M Cunningham, Evelyn Despierre, Jennifer A Doherty, Thilo Dörk, Matthias Dürst, Diana M Eccles, Arif B Ekici, Douglas Easton, Peter A Fasching, Anna de Fazio, David A Fenstermacher, James M Flanagan, Brooke L Fridley, Eitan Friedman, Bo Gao, Olga Sinilnikova, Aleksandra Gentry-Maharaj, Andrew K Godwin, Ellen L Goode, Marc T Goodman, Jenny Gross, Thomas V O Hansen, Paul Harnett, Matti Rookus, Tuomas Heikkinen, Rebecca Hein, Claus Høgdall, Estrid Høgdall, Edwin S Iversen, Anna Jakubowska, Sharon E Johnatty, Beth Y Karlan, Noah D Kauff, Stanley B Kaye, Georgia Chenevix-Trench, Linda E Kelemen, Lambertus A Kiemeney, Susanne Krüger Kjaer, Diether Lambrechts, James P LaPolla, Conxi Lazaro, Nhu D Le, Arto Leminen, Karin Leunen, Douglas A Levine, Yi Lu, Lene Lundvall, Stuart MacGregor, Tamara Marees, Leon F Massuger, John R McLaughlin, Usha Menon, Marco Montagna, Kirsten B Moysich, Steven A Narod, Katherine L Nathanson, Lotte Nedergaard, Roberta B Ness, Heli Nevanlinna, Stefan Nickels, Ana Osorio, Jim Paul, Celeste Leigh Pearce, Catherine M Phelan, Malcolm C Pike, Paolo Radice, Mary Anne Rossing, Joellen M Schildkraut, Thomas A Sellers, Christian F Singer, Honglin Song, Daniel O Stram, Rebecca Sutphen, Annika Lindblom, Kathryn L Terry, Ya-Yu Tsai, Anne M Van Altena, Ignace Vergote, Robert A Vierkant, Allison F Vitonis, Christine Walsh, Shan Wang-Gohrke, Barbara Wappenschmidt, Anna H Wu, Argyrios Ziogas, Andrew Berchuck, Harvey A Risch.
Clin. Cancer Res.
PUBLISHED: 03-08-2011
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An assay for the single-nucleotide polymorphism (SNP), rs61764370, has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3-UTR miRNA binding site of the KRAS oncogene and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published article, analyzing fewer than 1,000 subjects in total, has examined this association.
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Cervicovaginal shedding of hepatitis C viral RNA is associated with the presence of menstrual or other blood in cervicovaginal fluids.
J. Clin. Virol.
PUBLISHED: 06-25-2010
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The role of sexual activity in hepatitis C virus (HCV) transmission remains controversial. Studies to date have not explored the relationship between HCV shedding in cervicovaginal fluids and the presence of menstrual or other blood.
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Retaining nursing faculty beyond retirement age.
Nurse Educ
PUBLISHED: 06-16-2010
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The number of nursing faculty planning to retire by 2020 is alarming. To develop strategies for retaining faculty, researchers asked: What factors influence the decision by nursing faculty to stay in the workforce past retirement age? What barriers could be removed that would encourage faculty to stay longer? Using Giorgis analysis method, findings from 6 faculty teaching past retirement age revealed key meaning units and grand themes that match Maslows Hierarchy of Inborn Needs.
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Mental illness: a modern-day leprosy?
J Christ Nurs
PUBLISHED: 04-07-2010
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Leprosy in the ancient world involved quarantine from family and society and great stigma. Similarly, mental illness today can involve separation, lost potential, and stigma. As with leprosy, most people misunderstand etiology, treatment, and prognosis in mental illness. Nurses are in a key position to educate, intervene, and improve mental health outcomes.
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Common variants at 19p13 are associated with susceptibility to ovarian cancer.
Kelly L Bolton, Jonathan Tyrer, Honglin Song, Susan J Ramus, Maria Notaridou, Chris Jones, Tanya Sher, Aleksandra Gentry-Maharaj, Eva Wozniak, Ya-Yu Tsai, Joanne Weidhaas, Daniel Paik, David J Van Den Berg, Daniel O Stram, Celeste Leigh Pearce, Anna H Wu, Wendy Brewster, Hoda Anton-Culver, Argyrios Ziogas, Steven A Narod, Douglas A Levine, Stanley B Kaye, Robert Brown, Jim Paul, James Flanagan, Weiva Sieh, Valerie McGuire, Alice S Whittemore, Ian Campbell, Martin E Gore, Jolanta Lissowska, Hanna P Yang, Krzysztof Mędrek, Jacek Gronwald, Jan Lubiński, Anna Jakubowska, Nhu D Le, Linda S Cook, Linda E Kelemen, Angela Brook-Wilson, Leon F A G Massuger, Lambertus A Kiemeney, Katja K H Aben, Anne M Van Altena, Richard Houlston, Ian Tomlinson, Rachel T Palmieri, Patricia G Moorman, Joellen Schildkraut, Edwin S Iversen, Catherine Phelan, Robert A Vierkant, Julie M Cunningham, Ellen L Goode, Brooke L Fridley, Susan Kruger-Kjaer, Jan Blaeker, Estrid Hogdall, Claus Hogdall, Jenny Gross, Beth Y Karlan, Roberta B Ness, Robert P Edwards, Kunle Odunsi, Kirsten B Moyisch, Julie A Baker, Francesmary Modugno, Tuomas Heikkinenen, Ralf Bützow, Heli Nevanlinna, Arto Leminen, Natalia Bogdanova, Natalia Antonenkova, Thilo Doerk, Peter Hillemanns, Matthias Dürst, Ingo Runnebaum, Pamela J Thompson, Michael E Carney, Marc T Goodman, Galina Lurie, Shan Wang-Gohrke, Rebecca Hein, Jenny Chang-Claude, Mary Anne Rossing, Kara L Cushing-Haugen, Jennifer Doherty, Chu Chen, Thorunn Rafnar, Soren Besenbacher, Patrick Sulem, Kari Stefansson, Michael J Birrer, Kathryn L Terry, Dena Hernandez, Daniel W Cramer, Ignace Vergote, Frédéric Amant, Diether Lambrechts, Evelyn Despierre, Peter A Fasching, Matthias W Beckmann, Falk C Thiel, Arif B Ekici, Xiaoqing Chen, , Sharon E Johnatty, Penelope M Webb, Jonathan Beesley, Stephen Chanock, Montserrat Garcia-Closas, Tom Sellers, Douglas F Easton, Andrew Berchuck, Georgia Chenevix-Trench, Paul D P Pharoah, Simon A Gayther.
Nat. Genet.
PUBLISHED: 04-05-2010
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Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 × 10?? and P = 6 × 10??, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 × 10?? and P = 4 × 10?¹¹, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.
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A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24.
Ellen L Goode, Georgia Chenevix-Trench, Honglin Song, Susan J Ramus, Maria Notaridou, Kate Lawrenson, Martin Widschwendter, Robert A Vierkant, Melissa C Larson, Susanne K Kjaer, Michael J Birrer, Andrew Berchuck, Joellen Schildkraut, Ian Tomlinson, Lambertus A Kiemeney, Linda S Cook, Jacek Gronwald, Montserrat Garcia-Closas, Martin E Gore, Ian Campbell, Alice S Whittemore, Rebecca Sutphen, Catherine Phelan, Hoda Anton-Culver, Celeste Leigh Pearce, Diether Lambrechts, Mary Anne Rossing, Jenny Chang-Claude, Kirsten B Moysich, Marc T Goodman, Thilo Dörk, Heli Nevanlinna, Roberta B Ness, Thorunn Rafnar, Claus Hogdall, Estrid Hogdall, Brooke L Fridley, Julie M Cunningham, Weiva Sieh, Valerie McGuire, Andrew K Godwin, Daniel W Cramer, Dena Hernandez, Douglas Levine, Karen Lu, Edwin S Iversen, Rachel T Palmieri, Richard Houlston, Anne M Van Altena, Katja K H Aben, Leon F A G Massuger, Angela Brooks-Wilson, Linda E Kelemen, Nhu D Le, Anna Jakubowska, Jan Lubiński, Krzysztof Mędrek, Anne Stafford, Douglas F Easton, Jonathan Tyrer, Kelly L Bolton, Patricia Harrington, Diana Eccles, Ann Chen, Ashley N Molina, Barbara N Davila, Hector Arango, Ya-Yu Tsai, Zhihua Chen, Harvey A Risch, John Mclaughlin, Steven A Narod, Argyrios Ziogas, Wendy Brewster, Aleksandra Gentry-Maharaj, Usha Menon, Anna H Wu, Daniel O Stram, Malcolm C Pike, , Jonathan Beesley, Penelope M Webb, Xiaoqing Chen, Arif B Ekici, Falk C Thiel, Matthias W Beckmann, Hannah Yang, Nicolas Wentzensen, Jolanta Lissowska, Peter A Fasching, Evelyn Despierre, Frédéric Amant, Ignace Vergote, Jennifer Doherty, Rebecca Hein, Shan Wang-Gohrke, Galina Lurie, Michael E Carney, Pamela J Thompson, Ingo Runnebaum, Peter Hillemanns, Matthias Dürst, Natalia Antonenkova, Natalia Bogdanova, Arto Leminen, Ralf Bützow, Tuomas Heikkinen, Kari Stefansson, Patrick Sulem, Soren Besenbacher, Thomas A Sellers, Simon A Gayther, Paul D P Pharoah.
Nat. Genet.
PUBLISHED: 03-26-2010
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Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P ? 10??) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P ? 5 × 10?? (8q24, P = 8.0 × 10?¹? and 2q31, P = 3.8 × 10?¹?) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10?? and 17q21, P = 1.4 × 10??). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.
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Associations of overall and abdominal adiposity with area and volumetric mammographic measures among postmenopausal women.
Int. J. Cancer
PUBLISHED: 03-26-2010
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Whereas mammographic density and adiposity are positively associated with postmenopausal breast cancer risk, they are inversely associated with one another. To examine the association between these two risk factors, a secondary analysis of data from a randomized controlled trial of a year-long aerobic exercise intervention was done. Participants were 302 postmenopausal women aged 50-74 years. Dense fibroglandular and nondense fatty tissue were measured from mammograms using computer-assisted thresholding software for area measurements and a technique relying on the calibration of mammography machines with a tissue-equivalent phantom for volumetric measurements. Adiposity was measured by anthropometry (body mass index, waist circumference), whole-body dual x-ray absorptiometry scans (body fat) and computed tomography scans (abdominal adiposity). Correlations were estimated between and within women, the latter representing the association between the 1-year change in adiposity and mammographic measures. Adiposity was correlated with nondense area and volume (0.50 ? r ? 0.66 between women; 0.18 ? r ? 0.46 within women). Between women, adiposity was correlated with dense area and volume (-0.12 ? r ? -0.30) and with percent dense area and volume (-0.28 ? r ? -0.48). Because measurements made with scans explained at most only 3% more of the variation in absolute or percent density beyond that explained by anthropometric measurements, anthropometric measurements are likely sufficient for adjustment of the association between mammographic density and breast cancer risk. Adiposity is associated with breast fatty tissue and possibly weakly inversely associated with fibroglandular tissue.
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Case-control study of lifetime total physical activity and endometrial cancer risk.
Cancer Causes Control
PUBLISHED: 03-08-2010
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A population-based case-control study of physical activity and endometrial cancer risk was conducted in Alberta between 2002 and 2006. Incident, histologically confirmed cases of endometrial cancer (n = 542) were frequency age-matched to controls (n = 1,032). The Lifetime Total Physical Activity Questionnaire was used to measure occupational, household, and recreational activity levels. Multivariable logistic regression analyses were conducted. Total lifetime physical activity reduced endometrial cancer risk (odds ratio [OR] for >129 vs. <82 MET-h/week/year = 0.86, 95% confidence interval [95% CI]: 0.63, 1.18). By type of activity, the risks were significantly decreased for greater recreational activity (OR = 0.64, 95% CI: 0.47, 0.87), but not for household activity (OR = 1.09, 95% CI: 0.75, 1.58) and/or occupational activity (OR = 0.90, 95% CI: 0.67, 1.20) when comparing the highest to lowest quartiles. For activity performed at different biologically defined life periods, some indication of reduced risks with activity done between menarche and full-term pregnancy and after menarche was observed. When examining the activity by intensity of activity (i.e., light <3, moderate 3-6, and vigorous >6 METs), light activity slightly decreased endometrial cancer risk (OR = 0.68, 95% CI: 0.48, 0.97) but no association with moderate or vigorous intensity activity was found. Endometrial cancer risk was increased with sedentary occupational activity by 28% (95 CI%: 0.89, 1.83) for >11.3 h/week/year versus
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A systematic literature review of vitamin D and ovarian cancer.
Am. J. Obstet. Gynecol.
PUBLISHED: 01-20-2010
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We assessed the evidence supporting a reduction in risk for ovarian cancer occurrence or mortality with greater vitamin D exposures.
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Clinical correlates of herpes simplex virus viremia among hospitalized adults.
Clin. Infect. Dis.
PUBLISHED: 10-08-2009
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Quantification of herpes simplex virus (HSV) DNA in the peripheral blood is often used to evaluate patients suspected of having disseminated HSV infection. Few studies have examined the clinical correlates of HSV viremia among adults.
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Women in substance abuse recovery: measures of resilience and self-differentiation.
West J Nurs Res
PUBLISHED: 06-11-2009
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The National Institute of Drug Abuse has promoted drug abuse research in the past two decades focusing on women and gender differences. One hundred twenty-eight Hispanic and White women have participated in this comparative descriptive study that has examined the differences between chemically dependent (CD) women in recovery and non-chemically dependent (non-CD) women in regard to resilience and self-differentiation-demographic variables associated with resilience and self-differentiation and recovery variables associated with resilience and self-differentiation in the CD women. Findings indicate that the CD women and Hispanic women have scored significantly lower on measures of resilience and self-differentiation. Among the recovery variables, resilience and self-differentiation are significant for children support but community support is not significant. The finding that Hispanic and White women in recovery score lower on resilience and self-differentiation is important for designing treatment strategies supportive of women in recovery.
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Colorectal cancer screening among first-degree relatives of colorectal cancer patients: benefits and barriers.
Ann. Surg. Oncol.
PUBLISHED: 03-04-2009
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Individuals with a first-degree family history of colorectal cancer (CRC) are at increased risk of CRC. Study objectives were: (1) to estimate the proportion of first-degree relatives (FDR) of CRC patients being screened for CRC and (2) to identify predictors of screened behavior.
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A cross-sectional study of intima-media thickness, ethnicity, metabolic syndrome, and cardiovascular risk in 2268 study participants.
Mayo Clin. Proc.
PUBLISHED: 03-03-2009
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To describe the association between intima-media thickness (IMT) and metabolic syndrome (MetS) and to examine if the addition of IMT to a traditional MetS definition adds value to the assessment of predicted cardiovascular disease (CVD) risk in a large multiethnic population.
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Distributed Drug Discovery, Part 2: global rehearsal of alkylating agents for the synthesis of resin-bound unnatural amino acids and virtual D(3) catalog construction.
J Comb Chem
PUBLISHED: 02-28-2009
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Distributed Drug Discovery (D(3)) proposes solving large drug discovery problems by breaking them into smaller units for processing at multiple sites. A key component of the synthetic and computational stages of D(3) is the global rehearsal of prospective reagents and their subsequent use in the creation of virtual catalogs of molecules accessible by simple, inexpensive combinatorial chemistry. The first section of this article documents the feasibility of the synthetic component of Distributed Drug Discovery. Twenty-four alkylating agents were rehearsed in the United States, Poland, Russia, and Spain, for their utility in the synthesis of resin-bound unnatural amino acids 1, key intermediates in many combinatorial chemistry procedures. This global reagent rehearsal, coupled to virtual library generation, increases the likelihood that any member of that virtual library can be made. It facilitates the realistic integration of worldwide virtual D(3) catalog computational analysis with synthesis. The second part of this article describes the creation of the first virtual D(3) catalog. It reports the enumeration of 24,416 acylated unnatural amino acids 5, assembled from lists of either rehearsed or well-precedented alkylating and acylating reagents, and describes how the resulting catalog can be freely accessed, searched, and downloaded by the scientific community.
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Comparison of methods for extraction of viral DNA from cellular specimens.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 01-07-2009
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The accuracy and precision of quantitative polymerase chain reaction (PCR) results depend not only on the PCR reaction but also on the extraction of viral nucleic acid. Although the extraction of viral nucleic acid from fluids has been extensively studied, less data are available regarding extractions from cellular specimens. We therefore evaluated several commercially available kits for the extraction of nucleic acid from cellular specimens. Although the kits generally performed well, there were some differences in extraction efficiency, especially at low numbers of input cells. Inclusion of a multivirus positive control allowed careful monitoring of extraction efficiency during routine clinical use. Laboratories are encouraged to validate extraction methods carefully in the context of the proposed viral testing.
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Comorbidities and endometrial cancer survival in Hispanics and non-Hispanic whites.
Cancer Causes Control
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We investigated comorbidities and endometrial cancer survival by ethnicity because Hispanic whites (HWs) have worse survival than non-Hispanic whites (NHWs).
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Allele-specific PCR for determination of IL28B genotype.
J. Clin. Microbiol.
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The IL28B genotype is a critical determinant of interferon response in patients infected with hepatitis C virus genotype 1. We describe an allele-specific PCR assay for the IL28B genotype. The assay is simple and robust, uses commonly available real-time PCR instrumentation, and is well suited for clinical laboratories offering IL28B genotyping.
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Case-control study of markers of insulin resistance and endometrial cancer risk.
Endocr. Relat. Cancer
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Markers of insulin resistance such as the adiponectin:leptin ratio (A:L) and the homeostasis model assessment ratio (HOMA-IR) are associated with obesity and hyperinsulinemia, both established risk factors for endometrial cancer, and may therefore be informative regarding endometrial cancer risk. This study investigated the association between endometrial cancer risk and markers of insulin resistance, namely adiponectin, leptin, the A:L ratio, insulin, fasting glucose, and the HOMA-IR. We analyzed data from 541 incident endometrial cancer cases and 961 frequency age-matched controls in a population-based case-control study in Alberta, Canada from 2002 to 2006. Participants completed interview-administered questionnaires were assessed for anthropometric measures, and provided 8-h fasting blood samples either pre- or postoperatively. Blood was analyzed for concentrations of leptin, adiponectin, and insulin by immunoassay, and fasting plasma glucose levels were determined by fluorimetric quantitative determination. Compared with the lowest quartile, the highest quartile of insulin and HOMA-IR was associated with 64% (95% confidence intervals (CI): 1.12-2.40) and 72% (95% CI: 1.17-2.53) increased risks of endometrial cancer, respectively, and the highest quartile of adiponectin was associated with a 45% (95% CI: 0.37-0.80) decreased risk after multivariable adjustments. Null associations were observed between fasting glucose, leptin and A:L, and endometrial cancer risk. This population-based study provides evidence for a role of insulin resistance in endometrial cancer etiology and may provide one possible pathway whereby obesity increases the risk of this common cancer. Interventions aimed at decreasing both obesity and insulin resistance may decrease endometrial cancer risk.
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Triangle of prevention: a unions experience promoting a systems-of-safety health and safety program.
New Solut
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After years of watching company health and safety programs fail to prevent major incidents, injuries, illness, and death in industrial workplaces, union health and safety staff and rank and file activists took up the challenge of creating a union-run alternative program. Named the Triangle of Prevention (TOP), the program successfully engages both local unions and management in incident and near-miss reporting and investigation, root cause analysis, recommending and tracking solutions, and learning and sharing lessons. In all phases, TOP uses a hierarchical, systems-of-safety-based approach to hazard identification, reporting, prevention and control while aiming to engage the union, its members, and all other employees of a worksite. This article explains the foundations and workings of this program, the role of an expansive worker-to-worker training regimen, and the ways in which the program has transformed workplaces.
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Genome-wide association study for ovarian cancer susceptibility using pooled DNA.
Twin Res Hum Genet
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Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in the previous studies, which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high-density Illumina 1M-Duo array. We followed up 20 of the most significantly associated SNPs, which are not well tagged by the lower density arrays used by the published GWAS, and genotyping them on individual DNA. Most of the top 20 SNPs were clearly validated by individually genotyping the samples used in the pools. However, none of the 20 SNPs replicated when tested for association in a much larger stage 2 set of 4,651 cases and 6,966 controls from the Ovarian Cancer Association Consortium. Given that most of the top 20 SNPs from pooling were validated in the same samples by individual genotyping, the lack of replication is likely to be due to the relatively small sample size in our stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by less dense arrays. However, our study lacked power to make clear statements on the existence of hitherto untagged small-effect variants.
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The impact of race and comorbidity on survival in endometrial cancer.
Cancer Epidemiol. Biomarkers Prev.
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Poorer survival from endometrial cancer in blacks than in whites is well documented. The aims of this study were to determine whether diabetes, hypertension, or other conditions influence survival and whether accounting for these conditions reduces this racial disparity.
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A review of cancer in U.S. Hispanic populations.
Cancer Prev Res (Phila)
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There are compelling reasons to conduct studies of cancer in Hispanics, the fastest growing major demographic group in the United States (from 15% to 30% of the U.S. population by 2050). The genetically admixed Hispanic population coupled with secular trends in environmental exposures and lifestyle/behavioral practices that are associated with immigration and acculturation offer opportunities for elucidating the effects of genetics, environment, and lifestyle on cancer risk and identifying novel risk factors. For example, traditional breast cancer risk factors explain less of the breast cancer risk in Hispanics than in non-Hispanic whites (NHW), and there is a substantially greater proportion of never-smokers with lung cancer in Hispanics than in NHW. Hispanics have higher incidence rates for cancers of the cervix, stomach, liver, and gall bladder than NHW. With respect to these cancers, there are intriguing patterns that warrant study (e.g., depending on country of origin, the five-fold difference in gastric cancer rates for Hispanic men but not Hispanic women). Also, despite a substantially higher incidence rate and increasing secular trend for liver cancer in Hispanics, there have been no studies of Hispanics reported to date. We review the literature and discuss study design options and features that should be considered in future studies.
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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.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.