Dataset Information

Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer.

ABSTRACT: There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied.Data from 14 ovarian cancer case-control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the presence of interactions for all histologic subtypes. A genetic "risk score" was created to consider the effects of all six variants simultaneously. A multivariate model was fit to examine the association between all environmental risk factors and genetic risk score on ovarian cancer risk.Among 7,374 controls and 5,566 cases, there was no statistical evidence of interaction between the six SNPs or genetic risk score and the environmental risk factors on ovarian cancer risk. In a main effects model, women in the highest genetic risk score quartile had a 65% increased risk of ovarian cancer compared with women in the lowest [95% confidence interval (CI), 1.48-1.84]. Analyses by histologic subtype yielded risk differences across subtype for endometriosis (Phet < 0.001), parity (Phet < 0.01), and tubal ligation (Phet = 0.041).The lack of interactions suggests that a multiplicative model is the best fit for these data. Under such a model, we provide a robust estimate of the effect of each risk factor that sets the stage for absolute risk prediction modeling that considers both environmental and genetic risk factors. Further research into the observed differences in risk across histologic subtype is warranted.

SUBMITTER: Pearce CL

PROVIDER: S-EPMC3963289 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer.

Pearce Celeste Leigh CL Rossing Mary Anne MA Lee Alice W AW Ness Roberta B RB Webb Penelope M PM Chenevix-Trench Georgia G Jordan Susan M SM Stram Douglas A DA Chang-Claude Jenny J Hein Rebecca R Nickels Stefan S Lurie Galina G Thompson Pamela J PJ Carney Michael E ME Goodman Marc T MT Moysich Kirsten K Hogdall Estrid E Jensen Allan A Goode Ellen L EL Fridley Brooke L BL Cunningham Julie M JM Vierkant Robert A RA Weber Rachel Palmieri RP Ziogas Argyrios A Anton-Culver Hoda H Gayther Simon A SA Gentry-Maharaj Aleksandra A Menon Usha U Ramus Susan J SJ Brinton Louise L Wentzensen Nicolas N Lissowska Jolanta J Garcia-Closas Montserrat M Massuger Leon F A G LF Kiemeney Lambertus A L M LA Van Altena Anne M AM Aben Katja K H KK Berchuck Andrew A Doherty Jennifer A JA Iversen Edwin E McGuire Valerie V Moorman Patricia G PG Pharoah Paul P Pike Malcolm C MC Risch Harvey H Sieh Weiva W Stram Daniel O DO Terry Kathryn L KL Whittemore Alice A Wu Anna H AH Schildkraut Joellen M JM Kjaer Susanne K SK

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20130305 5

<h4>Background</h4>There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied.<h4>Methods</h4>Data from 14 ovarian cancer case-control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the pr ...[more]

PMID: 23462924

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Project description:Background & aimsNortheast Iran has one of the highest reported rates of esophageal squamous cell carcinoma (ESCC) worldwide. Decades of investigations in this region have identified some local habits and environmental exposures that increase risk. We analyzed data from the Golestan Cohort Study to determine the individual and combined effects of the major environmental risk factors of ESCC.MethodsWe performed a population-based cohort of 50,045 individuals, 40 to 75 years old, from urban and rural areas across Northeast Iran. Detailed data on demographics, diet, lifestyle, socioeconomic status, temperature of drinking beverages, and different exposures were collected using validated methods, questionnaires, and physical examinations, from 2004 through 2008. Participants were followed from the date of enrollment to the date of first diagnosis of esophageal cancer, date of death from other causes, or date of last follow-up, through December 31, 2017. Proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between different exposures and ESCC.ResultsDuring an average 10 years of follow-up, 317 participants developed ESCC. Opium smoking (HR 1.85; 95% CI 1.18-2.90), drinking hot tea (≥60°C) (HR 1.60; 95% CI 1.15-2.22), low intake of fruits (HR 1.48; 95% CI 1.07-2.05) and vegetables (HR 1.62; 95% CI 1.03-2.56), excessive tooth loss (HR 1.66; 95% CI 1.04-2.64), drinking unpiped water (HR 2.04; 95% CI 1.09-3.81), and exposure to indoor air pollution (HR 1.57; 95% CI 1.08-2.29) were significantly associated with increased risk of ESCC, in a dose-dependent manner. Combined exposure to these risk factors was associated with a stepwise increase in the risk of developing ESCC, reaching a more than 7-fold increase in risk in the highest category. Approximately 75% of the ESCC cases in this region can be attributed to a combination of the identified exposures.ConclusionsAnalysis of data from the Golestan Cohort Study in Iran identified multiple risk factors for ESCC in this population. Our findings support the hypothesis that the high rates of ESCC are due to a combination of factors, including thermal injury (from hot tea), exposure to polycyclic aromatic hydrocarbons (from opium and indoor air pollution), and nutrient-deficient diets. We also associated ESCC risk with exposure to unpiped water and tooth loss.

Dataset Information

Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer.

Publications

Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer.

Similar Datasets

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