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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 20, 2019
- Source ID
- 10.1002/ijc.32029
Entities
People
- Alice S. Whittemore
- Alice W. Lee
- Allan Jensen
- Andrew Berchuck
- Angela Brooks‐wilson
- Anna H. Wu
- Argyrios Ziogas
- Ashley Wiensch
- Bhramar Mukherjee
- Britton Trabert
- Celeste Leigh Pearce
- Daniel W. Cramer
- David Huntsman
- Elisa V. Bandera
- Ellen L Goode
- Estrid Høgdall
- Francesmary Modugno
- Gang Liu
- Georgia Chenevix‐trench
- Graham Giles
- Hoda Anton-Culver
- Holly R Harris
- Honglin Song
- Jennifer A Doherty
- Jenny Chang‐claude
- Joellen M. Schildkraut
- Jonathan P Tyrer
- Kathryn L. Terry
- Linda S. Cook
- Malcolm C Pike
- Marc T. Goodman
- Mary Anne Rossing
- Maxwell Salvatore
- Miao Wang
- Nhu D. Le
- Nico Wentzensen
- Pamela J. Thompson
- Paul D.p. Pharoah
- Penelope M. Webb
- Renée Turzanski Fortner
- Roberta B. Ness
- Roger L. Milne
- Sara H. Olson
- Sehee Kim
- Shelley S. Tworoger
- Simon A Gayther
- Stacey J Winham
- Susanne Krüger Kjaer
- Usha Menon
- Weiva Sieh
Organizations
- Alberta Health Services
- BC Cancer Agency
- Brigham and Women's Hospital
- California State University
- Canadian Institutes of Health Research
- Cancer Council Victoria
- Cedars-Sinai Medical Center
- Connecticut Department of Public Health
- Danish Cancer Society
- Duke University
- Fred Hutchinson Cancer Center
- German Cancer Research Center
- H. Lee Moffitt Cancer Center & Research Institute
- Harvard University
- Icahn School of Medicine at Mount Sinai
- Mayo Clinic
- Mayo Foundation for Medical Education and Research
- Memorial Sloan Kettering Cancer Center
- Minnesota Ovarian Cancer Alliance
- Monash University
- National Cancer Institute
- National Center for Research Resources
- National Health and Medical Research Council
- National Institute of Environmental Health Sciences
- National Institutes of Health
- National Science Foundation
- Ovarian Cancer Australia
- Ovarian Cancer Research Alliance
- QIMR Berghofer Medical Research Institute
- Rutgers University
- Seventh Framework Programme
- Simon Fraser University
- Stanford University
- United States Army Medical Research and Development Command
- United States Department of Defense
- University College London
- University of British Columbia
- University of California, Irvine
- University of Cambridge
- University of Copenhagen
- University of Melbourne
- University of Michigan
- University of New Mexico
- University of Pittsburgh
- University of Pittsburgh School of Medicine
- University of Southern California
- University of Texas at Austin
- University of Utah
- University of Virginia
- University of Washington