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

Sehee Kim; Miao Wang; Jonathan P Tyrer; Allan Jensen; Ashley Wiensch; Gang Liu; Alice W Lee; Roberta B Ness; Maxwell Salvatore; Shelley S Tworoger; Alice S Whittemore; Hoda Anton-Culver; Weiva Sieh; Sara H Olson; Andrew Berchuck; Ellen L Goode; Marc T Goodman; Jennifer Anne Doherty; Georgia Chenevix-Trench; Mary Anne Rossing; Penelope M Webb; Graham G Giles; Kathryn L Terry; Argyrios Ziogas; Renée T Fortner; Usha Menon; Simon A Gayther; Anna H Wu; Honglin Song; Angela Brooks-Wilson; Elisa V Bandera; Linda S Cook; Daniel W Cramer; Roger L Milne; Stacey J Winham; Susanne K Kjaer; Francesmary Modugno; Pamela J Thompson; Jenny Chang-Claude; Holly R Harris; Joellen M Schildkraut; Nhu D Le; Nico Wentzensen; Britton Trabert; Estrid Høgdall; David Huntsman; Malcolm C Pike; Paul D P Pharoah; Celeste Leigh Pearce; Bhramar Mukherjee

doi:10.1002/ijc.32029

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

Journal article

Open access

Peer reviewed

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

Sehee Kim, Miao Wang, Jonathan P Tyrer, Allan Jensen, Ashley Wiensch, Gang Liu, Alice W Lee, Roberta B Ness, Maxwell Salvatore, Shelley S Tworoger, …

International journal of cancer, Vol.144(9), pp.2192-2205

05/01/2019

DOI: https://doi.org/10.1002/ijc.32029

PMCID: PMC6399057

PMID: 30499236

Abstract

Case-Control Studies

Contraceptives, Oral, Hormonal

Environment

Environmental Exposure - adverse effects

Female

Gene-Environment Interaction

Genetic Predisposition to Disease - genetics

Genome-Wide Association Study - methods

Genotype

Humans

Ovarian Neoplasms - etiology

Ovarian Neoplasms - genetics

Polymorphism, Single Nucleotide - genetics

Risk

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 ). 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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Title: A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants
Creators: Sehee Kim - Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
Miao Wang - Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
Jonathan P Tyrer - Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom
Allan Jensen - Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
Ashley Wiensch - Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
Gang Liu - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Alice W Lee - Department of Public Health, California State University, Fullerton, Fullerton, CA, USA
Roberta B Ness - University of Texas School of Public Health, Houston, TX, USA
Maxwell Salvatore - Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
Shelley S Tworoger - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Alice S Whittemore - Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA
Hoda Anton-Culver - Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA
Weiva Sieh - Department of Genetics and Genomic Sciences, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Sara H Olson - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Andrew Berchuck - Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA
Ellen L Goode - Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Marc T Goodman - Department of Biomedical Sciences, Cedars-Sinai Medical Center, Community and Population Health Research Institute, Los Angeles, CA, USA
Jennifer Anne Doherty - Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
Georgia Chenevix-Trench - Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Mary Anne Rossing - Department of Epidemiology, University of Washington, Seattle, WA, USA
Penelope M Webb - Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Graham G Giles - Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia
Kathryn L Terry - Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA
Argyrios Ziogas - Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA
Renée T Fortner - Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Usha Menon - Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom
Simon A Gayther - Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Anna H Wu - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Honglin Song - Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom
Angela Brooks-Wilson - Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
Elisa V Bandera - Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
Linda S Cook - Division of Cancer Care, Department of Population Health Research, Alberta Health Services, Calgary, AB, Canada
Daniel W Cramer - Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA
Roger L Milne - Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
Stacey J Winham - Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Susanne K Kjaer - Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Francesmary Modugno - Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Pamela J Thompson - Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Jenny Chang-Claude - Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Holly R Harris - Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Joellen M Schildkraut - Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
Nhu D Le - Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada
Nico Wentzensen - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Britton Trabert - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Estrid Høgdall - Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
David Huntsman - Department of Pathology and Laboratory Medicine, and Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
Malcolm C Pike - Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Paul D P Pharoah - Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
Celeste Leigh Pearce - Center for Cancer Prevention and Translational Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Bhramar Mukherjee - Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
Publication Details: International journal of cancer, Vol.144(9), pp.2192-2205
Date published: 05/01/2019
Grant note: R03 CA113148 / NCI NIH HHS N01 CN025403 / NCI NIH HHS Department of Health T32 ES013678 / NIEHS NIH HHS R01 CA058860 / NCI NIH HHS K22 CA193860 / NCI NIH HHS UM1 CA176726 / NCI NIH HHS K22 CA138563 / NCI NIH HHS R01 CA160669 / NCI NIH HHS 10119 / Cancer Research UK R01 CA063678 / NCI NIH HHS R03 CA115195 / NCI NIH HHS P30 CA015083 / NCI NIH HHS K07 CA095666 / NCI NIH HHS R01 CA112523 / NCI NIH HHS U01 CA069417 / NCI NIH HHS R01 CA058598 / NCI NIH HHS M01 RR000056 / NCRR NIH HHS P01 CA017054 / NCI NIH HHS 10124 / Cancer Research UK P50 CA159981 / NCI NIH HHS U19 CA148112 / NCI NIH HHS R01 CA067262 / NCI NIH HHS R01 CA080742 / NCI NIH HHS P50 CA105009 / NCI NIH HHS R01 CA083918 / NCI NIH HHS R01 CA074850 / NCI NIH HHS N01 PC067010 / NCI NIH HHS R01 CA054419 / NCI NIH HHS R01 CA095023 / NCI NIH HHS K07 CA080668 / NCI NIH HHS R01 CA076016 / NCI NIH HHS R21 ES020811 / NIEHS NIH HHS P01 CA087969 / NCI NIH HHS P30 CA046592 / NCI NIH HHS P30 CA008748 / NCI NIH HHS MOP-86727 / CIHR UM1 CA186107 / NCI NIH HHS R01 CA087538 / NCI NIH HHS P50 CA136393 / NCI NIH HHS R01 CA122443 / NCI NIH HHS R01 CA049449 / NCI NIH HHS P30 CA014089 / NCI NIH HHS P30 CA072720 / NCI NIH HHS
Academic Unit: Cancer Epidemiology and Health Outcomes
Language: English
Resource Type: Journal article
Identifiers: 991031666378104646