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Cancer Epidemiol Biomarkers Prev. 2015 Nov;24(11):1731-8. doi: 10.1158/1055-9965.EPI-15-0392. Epub 2015 Sep 12.

Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women.

Author information

1
Division of General Internal Medicine, Department of Medicine, Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California. laura.fejerman@ucsf.edu.
2
Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, California.
3
Cancer Prevention Institute of California, Fremont, California and Department of Health Research and Policy (Epidemiology), and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.
4
Instituto Nacional de Salud Pública, Centro de Investigación en Salud Poblacional, Cuernavaca, Morelos, Mexico.
5
Department of Biology, University of Colorado at Colorado Springs, Colorado Springs, Colorado.
6
Department of Medicine, University of Utah, Salt Lake City, Utah.
7
Department of Epidemiology and Population Health, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.
8
Moffitt Cancer Center, Tampa, Florida.
9
Division of General Internal Medicine, Department of Medicine, Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California.

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.

PMID:
26364163
PMCID:
PMC4633366
DOI:
10.1158/1055-9965.EPI-15-0392
[Indexed for MEDLINE]
Free PMC Article

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