Association of Common Genetic Variants With Contralateral Breast Cancer Risk in the WECARE Study

Mark E Robson; Anne S Reiner; Jennifer D Brooks; Patrick J Concannon; Esther M John; Lene Mellemkjaer; Leslie Bernstein; Kathleen E Malone; Julia A Knight; Charles F Lynch; Meghan Woods; Xiaolin Liang; Robert W Haile; David J Duggan; Roy E Shore; Susan A Smith; Duncan C Thomas; Daniel O Stram; Jonine L Bernstein; WECARE Study Collaborative Group

doi:10.1093/jnci/djx051

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Association of Common Genetic Variants With Contralateral Breast Cancer Risk in the WECARE Study

Journal article

Open access

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Association of Common Genetic Variants With Contralateral Breast Cancer Risk in the WECARE Study

Mark E Robson, Anne S Reiner, Jennifer D Brooks, Patrick J Concannon, Esther M John, Lene Mellemkjaer, Leslie Bernstein, Kathleen E Malone, Julia A Knight, Charles F Lynch, …

JNCI : Journal of the National Cancer Institute, Vol.109(10), djx051

10/01/2017

DOI: 10.1093/jnci/djx051

PMCID: PMC5939625

PMID: 28521362

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Abstract

Women with unilateral breast cancer (UBC) are at risk of developing a subsequent contralateral breast cancer (CBC). Common variants are associated with breast cancer risk. Whether these influence CBC risk is unknown. Participants were breast cancer cases from the population-based Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study. Sixty-seven established breast cancer risk loci were genotyped directly or by imputation in 1459 case subjects with CBC and 2126 UBC control subjects. An unweighted polygenic risk score (PRS) was created by summing the number of risk alleles for each directly genotyped single nucleotide polymorphism (SNP), or for imputed loci, the imputed dosage. A weighted PRS was calculated similarly, but where each SNP's contribution was weighted by the published per-allele log odds ratio. Unweighted and weighted polygenic risk scores and CBC risk were modeled using conditional logistic regression. Cumulative CBC risk was estimated and benchmarked using Surveillance, Epidemiology, and End Results population incidence rates. Both unweighted and weighted PRS were statistically significantly associated with CBC risk. The adjusted risk ratio of CBC in women in the upper quartile of unweighted PRS compared with the lowest quartile was 1.63 (95% confidence interval [CI] = 1.33 to 2.00). The estimated 10-year cumulative risk for women in the upper quartile of the unweighted PRS was 7.4% (95% CI = 6.0% to 9.1%). For women in the upper quartile of the weighted PRS, the risk ratio for CBC was 1.75 (95% CI = 1.41 to 2.18) compared with women in the lowest quartile. There was no statistically significant heterogeneity by age, treatment (radiation therapy dose, tamoxifen, chemotherapy), estrogen receptor status of the first primary, histology of the first primary, length of at-risk period for CBC, or breast cancer family history. Common genomic variants associated with the development of first primary breast cancer are also associated with the development of CBC; the risk is strongest among those who carry more risk alleles.

United States

Genetic Predisposition to Disease

SEER Program

Genetic Association Studies

Humans

Middle Aged

Case-Control Studies

Young Adult

Breast Neoplasms - genetics

Breast Neoplasms - pathology

Adult

Female

Neoplasm Recurrence, Local - genetics

Neoplasm Recurrence, Local - epidemiology

Polymorphism, Single Nucleotide

Environmental Exposure - statistics & numerical data

Breast Neoplasms - epidemiology

Details

Title: Subtitle: Association of Common Genetic Variants With Contralateral Breast Cancer Risk in the WECARE Study
Creators: Mark E Robson - Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY, USA
Anne S Reiner - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York,NY, USA
Jennifer D Brooks - Epidemiology Division, University of Toronto, Dalla Lana School of Public Health Sciences, Toronto, ON, Canada
Patrick J Concannon - Genetics Institute, University of Florida, Gainesville, FL, USA
Esther M John - Stanford School of Medicine, Stanford, CA, USA
Lene Mellemkjaer - Danish Cancer Society, Copenhagen, Denmark
Leslie Bernstein - Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Kathleen E Malone - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Julia A Knight - Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
Charles F Lynch - Department of Epidemiology, University of Iowa, Iowa City, IA, USA
Meghan Woods - Memorial Sloan Kettering Cancer Center, New York, NY, USA
Xiaolin Liang - Memorial Sloan Kettering Cancer Center, New York, NY, USA
Robert W Haile - Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, California
David J Duggan - Integrated Cancer Genomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA
Roy E Shore - Department of Population Health, New York University, New York, NY, USA
Susan A Smith - Department of Radiation Physics, University of Texas, MD Anderson Cancer Center, Houston, TX, USA
Duncan C Thomas - Division of Biostatistics and Genetic Epidemiology, University of Southern California, Los Angeles, CA, USA
Daniel O Stram - Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
Jonine L Bernstein - Memorial Sloan Kettering Cancer Center, New York, NY, USA
WECARE Study Collaborative Group
Resource Type: Journal article
Publication Details: JNCI : Journal of the National Cancer Institute, Vol.109(10), djx051
DOI: 10.1093/jnci/djx051
PMID: 28521362
PMCID: PMC5939625
NLM abbreviation: J Natl Cancer Inst
ISSN: 1460-2105
eISSN: 1460-2105
Publisher: Oxford University Press; United States
Grant note: R01 CA129639 / NCI NIH HHS P30 CA008748 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 10/01/2017
Academic Unit: Epidemiology
Record Identifier: 9983996197502771

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