| Literature DB >> 30499236 |
Sehee Kim1, Miao Wang1, Jonathan P Tyrer2, Allan Jensen3, Ashley Wiensch4, Gang Liu5, Alice W Lee6, Roberta B Ness7, Maxwell Salvatore1,4, Shelley S Tworoger8,9, Alice S Whittemore10,11, Hoda Anton-Culver12, Weiva Sieh13, Sara H Olson14, Andrew Berchuck15, Ellen L Goode16, Marc T Goodman17,18, Jennifer Anne Doherty19, Georgia Chenevix-Trench20, Mary Anne Rossing21,22, Penelope M Webb23, Graham G Giles24,25,26, Kathryn L Terry9,27, Argyrios Ziogas12, Renée T Fortner28, Usha Menon29, Simon A Gayther30,31,32, Anna H Wu30, Honglin Song2, Angela Brooks-Wilson33,34, Elisa V Bandera35, Linda S Cook36,37, Daniel W Cramer9,27, Roger L Milne24,25,38, Stacey J Winham16, Susanne K Kjaer3,39, Francesmary Modugno40,41,42, Pamela J Thompson17, Jenny Chang-Claude28,43, Holly R Harris21, Joellen M Schildkraut44, Nhu D Le45, Nico Wentzensen46, Britton Trabert46, Estrid Høgdall3,47, David Huntsman48,49, Malcolm C Pike14,50, Paul D P Pharoah2,51, Celeste Leigh Pearce4,31, Bhramar Mukherjee1.
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.Entities:
Keywords: G × E; additive interaction; genetics; ovarian cancer
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Year: 2019 PMID： 30499236 PMCID： PMC6399057 DOI： 10.1002/ijc.32029
Source DB: PubMed Journal: Int J Cancer ISSN： 0020-7136 Impact factor: 7.396