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A comprehensive gene–environment interaction analysis in Ovarian Cancer using genome‐wide significant common variants

Authors: Elisa V. Bandera; Jonathan Tyrer; Gang Liu; Roger L. Milne; Roger L. Milne; Roger L. Milne; Nhu D. Le; +57 Authors

A comprehensive gene–environment interaction analysis in Ovarian Cancer using genome‐wide significant common variants

Abstract

As a follow‐up to genome‐wide association analysis of common variants associated with ovarian carcinoma (cancer), our study considers seven well‐known ovarian cancer risk factors and their interactions with 28 genome‐wide significant common genetic variants. The interaction analyses were based on data from 9971 ovarian cancer cases and 15,566 controls from 17 case–control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs. never) and rs13255292 (p value = 3.48 × 10−4). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI = 0.46–0.60) compared to 0.71 (95%CI = 0.66–0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1–5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene–environment analysis in ovarian cancer.

Countries
Denmark, United States, Australia, United Kingdom, United Kingdom
Keywords

Oral, Risk, additive interaction, Genotype, Oncology and Carcinogenesis, 610, Environment, Oncology and Hematology, Polymorphism, Single Nucleotide, G Ã E, Ovarian Neoplasms/etiology, Contraceptives, Oral, Hormonal, Rare Diseases, G × E, Health Sciences, Genetics, 2.1 Biological and endogenous factors, Humans, Genetic Predisposition to Disease, genetics, Oncology & Carcinogenesis, Polymorphism, Cancer, Ovarian Neoplasms, Biomedical and Clinical Sciences, Hormonal, Genetic Predisposition to Disease/genetics, Prevention, Human Genome, Contraceptives, Oncology and carcinogenesis, Single Nucleotide, Environmental Exposure, Ovarian Cancer, Good Health and Well Being, ovarian cancer, Case-Control Studies, Genome-Wide Association Study/methods, Women's Health, Female, Gene-Environment Interaction, Patient Safety, G x E, Single Nucleotide/genetics, Environmental Exposure/adverse effects, Genome-Wide Association Study

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    12
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
12
Top 10%
Average
Top 10%
Green
bronze