Kim, S;
Wang, M;
Tyrer, JP;
Jensen, A;
Wiensch, A;
Liu, G;
Lee, AW;
... Mukherjee, B; + view all
(2019)
A comprehensive gene–environment interaction analysis in Ovarian Cancer using genome‐wide significant common variants.
International Journal of Cancer
, 144
(9)
pp. 2192-2205.
10.1002/ijc.32029.
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Abstract
As a follow-up to genome-wide association analysis of common variants associated with ovarian carcinoma (cancer), this 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 9,971 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 x 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. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | A comprehensive gene–environment interaction analysis in Ovarian Cancer using genome‐wide significant common variants |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/ijc.32029 |
| Publisher version: | https://doi.org/10.1002/ijc.32029 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | G x E, additive interaction, genetics, ovarian cancer |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10064189 |
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