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Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors
- Source :
- Cancer Epidemiology, Biomarkers & Prevention, 25, 780-90, ResearcherID, Cancer Epidemiology, Biomarkers & Prevention, 25, 5, pp. 780-90
- Publication Year :
- 2016
-
Abstract
- Background: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene–environment interactions related to hormone-related risk factors could differ between obese and non-obese women. Methods: We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case–control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed. Results: SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, P = 4.9 × 10−6) and ESR1 (rs12661437, endometriosis, histology = all, P = 1.5 × 10−5). The most notable obesity–gene–hormone risk factor interaction was within INSR (rs113759408, parity, histology = endometrioid, P = 8.8 × 10−6). Conclusions: We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2. Future work is needed to develop powerful statistical methods able to detect these complex interactions. Impact: Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. Cancer Epidemiol Biomarkers Prev; 25(5); 780–90. ©2016 AACR.
- Subjects :
- 0301 basic medicine
Candidate gene
Epidemiology
medicine.drug_class
medicine.medical_treatment
Bioinformatics
Polymorphism, Single Nucleotide
Article
03 medical and health sciences
0302 clinical medicine
Risk Factors
Medicine
Humans
Obesity
Risk factor
Gene–environment interaction
Ovarian Neoplasms
Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17]
business.industry
Cancer
Hormone replacement therapy (menopause)
Middle Aged
medicine.disease
030104 developmental biology
Oncology
Genetic epidemiology
Estrogen
Urological cancers Radboud Institute for Health Sciences [Radboudumc 15]
030220 oncology & carcinogenesis
Female
Gene-Environment Interaction
Hormone therapy
business
Subjects
Details
- ISSN :
- 10559965
- Database :
- OpenAIRE
- Journal :
- Cancer Epidemiology, Biomarkers & Prevention, 25, 780-90, ResearcherID, Cancer Epidemiology, Biomarkers & Prevention, 25, 5, pp. 780-90
- Accession number :
- edsair.doi.dedup.....e21b95ab232a5b86af441f02b202dd76