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Association of Common Genetic Variants With Contralateral Breast Cancer Risk in the WECARE Study.
- Source :
-
Journal of the National Cancer Institute [J Natl Cancer Inst] 2017 Oct 01; Vol. 109 (10). - Publication Year :
- 2017
-
Abstract
- Background: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusions: 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.<br /> (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Adult
Breast Neoplasms pathology
Case-Control Studies
Environmental Exposure statistics & numerical data
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Middle Aged
SEER Program
United States
Young Adult
Breast Neoplasms epidemiology
Breast Neoplasms genetics
Neoplasm Recurrence, Local epidemiology
Neoplasm Recurrence, Local genetics
Polymorphism, Single Nucleotide
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2105
- Volume :
- 109
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of the National Cancer Institute
- Publication Type :
- Academic Journal
- Accession number :
- 28521362
- Full Text :
- https://doi.org/10.1093/jnci/djx051