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A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants.

Publication ,  Journal Article
Kim, S; Wang, M; Tyrer, JP; Jensen, A; Wiensch, A; Liu, G; Lee, AW; Ness, RB; Salvatore, M; Tworoger, SS; Whittemore, AS; Anton-Culver, H ...
Published in: Int J Cancer
May 1, 2019

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.

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

May 1, 2019

Volume

144

Issue

9

Start / End Page

2192 / 2205

Location

United States

Related Subject Headings

  • Risk
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Gene-Environment Interaction
  • Female
 

Citation

APA
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Kim, S., Wang, M., Tyrer, J. P., Jensen, A., Wiensch, A., Liu, G., … Mukherjee, B. (2019). A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants. Int J Cancer, 144(9), 2192–2205. https://doi.org/10.1002/ijc.32029
Kim, Sehee, Miao Wang, Jonathan P. Tyrer, Allan Jensen, Ashley Wiensch, Gang Liu, Alice W. Lee, et al. “A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants.Int J Cancer 144, no. 9 (May 1, 2019): 2192–2205. https://doi.org/10.1002/ijc.32029.
Kim S, Wang M, Tyrer JP, Jensen A, Wiensch A, Liu G, et al. A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants. Int J Cancer. 2019 May 1;144(9):2192–205.
Kim, Sehee, et al. “A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants.Int J Cancer, vol. 144, no. 9, May 2019, pp. 2192–205. Pubmed, doi:10.1002/ijc.32029.
Kim S, Wang M, Tyrer JP, Jensen A, Wiensch A, Liu G, Lee AW, Ness RB, Salvatore M, Tworoger SS, Whittemore AS, Anton-Culver H, Sieh W, Olson SH, Berchuck A, Goode EL, Goodman MT, Doherty JA, Chenevix-Trench G, Rossing MA, Webb PM, Giles GG, Terry KL, Ziogas A, Fortner RT, Menon U, Gayther SA, Wu AH, Song H, Brooks-Wilson A, Bandera EV, Cook LS, Cramer DW, Milne RL, Winham SJ, Kjaer SK, Modugno F, Thompson PJ, Chang-Claude J, Harris HR, Schildkraut JM, Le ND, Wentzensen N, Trabert B, Høgdall E, Huntsman D, Pike MC, Pharoah PDP, Pearce CL, Mukherjee B. A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants. Int J Cancer. 2019 May 1;144(9):2192–2205.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

May 1, 2019

Volume

144

Issue

9

Start / End Page

2192 / 2205

Location

United States

Related Subject Headings

  • Risk
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Gene-Environment Interaction
  • Female