Interaction between Common Breast Cancer Susceptibility Variants, Genetic Ancestry, and Nongenetic Risk Factors in Hispanic Women
Year: 2015
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. METHODS: We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. RESULTS: We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, <12 months, and >12 months breastfeeding, respectively, Pinteraction 0.014]. CONCLUSIONS: The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. IMPACT: These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk.
Institutions: University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, University of Southern California, USC Norris Comprehensive Cancer Center, Cancer Prevention Institute of California, Stanford Cancer Institute, Stanford University, Instituto Nacional de Salud Pública, University of Colorado Colorado Springs, University of Utah, University of Louisville, Moffitt Cancer Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: BREAST CANCER RISK FACTORS IN HISPANIC WOMEN, G1898402724, G198752013, G2255647278, VITAMIN D RECEPTOR GENE POLYMORPHISM AND BREAST CANCER, SURVEILLANCE EPIDEMIOLOGY &END RESULTS PROGRAM, G2925750098, G2970228389, G3083503531, G3707935348, FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY, Genome wide association study of breast cancer subtype and survival in Latinas, FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY, G4872765682, THE 4 CORNERS BREAST AND ENDOMETRIAL CANCER STUDY, FOUR-CORNERS BREAST CANCER STUDY, G592384189, Admixture Mapping for Breast Cancer in Latinas, G6490086502, Redes En Accion::The National Hispanic/Latino Cancer Network Research Network, Genetics of mammographic density and breast cancer risk in Latinas, Germline and Tumor Genomic Analyses of Breast Cancer in Latinas, Disparities in Breast Cancer: Development and Survival in Hispanic and NHW Women, Center for Aging in Diverse Communities: Ending Health Inequities in Older Adults, G908924418, G996001456
OpenAlex ID: W2213893281