Genetic ancestry modifies the association between genetic risk variants and breast cancer risk among Hispanic and non-Hispanic white women
Year: 2013
Type: article
Study design: Observational Study
Abstract: Hispanic women in the USA have lower breast cancer incidence than non-Hispanic white (NHW) women. Genetic factors may contribute to this difference. Breast cancer genome-wide association studies (GWAS) conducted in women of European or Asian descent have identified multiple risk variants. We tested the association between 10 previously reported single nucleotide polymorphisms (SNPs) and risk of breast cancer in a sample of 4697 Hispanic and 3077 NHW women recruited as part of three population-based case-control studies of breast cancer. We used stratified logistic regression analyses to compare the associations with different genetic variants in NHWs and Hispanics classified by their proportion of Indigenous American (IA) ancestry. Five of 10 SNPs were statistically significantly associated with breast cancer risk. Three of the five significant variants (rs17157903-RELN, rs7696175-TLR1 and rs13387042-2q35) were associated with risk among Hispanics but not in NHWs. The odds ratio (OR) for the heterozygous at 2q35 was 0.75 [95% confidence interval (CI) = 0.50-1.15] for low IA ancestry and 1.38 (95% CI = 1.04-1.82) for high IA ancestry (P interaction 0.02). The ORs for association at RELN were 0.87 (95% CI = 0.59-1.29) and 1.69 (95% CI = 1.04-2.73), respectively (P interaction 0.03). At the TLR1 locus, the ORs for women homozygous for the rare allele were 0.74 (95% CI = 0.42-1.31) and 1.73 (95% CI = 1.19-2.52) (P interaction 0.03). Our results suggest that the proportion of IA ancestry modifies the magnitude and direction of the association of 3 of the 10 previously reported variants. Genetic ancestry should be considered when assessing risk in women of mixed descent and in studies designed to discover causal mutations.
Source: Carcinogenesis
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 Medicine, 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: bronze
Awards: BREAST CANCER RISK FACTORS IN HISPANIC WOMEN, G1554522753, G1898402724, G198752013, G2255647278, VITAMIN D RECEPTOR GENE POLYMORPHISM AND BREAST CANCER, SURVEILLANCE EPIDEMIOLOGY &END RESULTS PROGRAM, G2925750098, G2970228389, G3083503531, G3707935348, REDES EN ACCION--CANCER AWARENESS, TRAINING AND RESEARCH, 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, 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: W2118933610