Abstract PR01: Genetic susceptibility, genetic ancestry, and breast cancer risk among Hispanic and non-Hispanic white women.
Authors: Fejerman Laura , Stern Mariana C. , Ziv Elad , John Esther M. , Torres-Mejia Gabriela , Hines Lisa M. , Wolff Roger , Wang Wei , Baumgartner Kathy , Giuliano Anna , Slattery Martha L. 
Published: August 2014

Abstract
U.S. Hispanic women have, on average, 30% lower breast cancer incidence than non-Hispanic white (NHW) women. Genetic risk heterogeneity 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. In the present study we tested the association between 10 previously reported single nucleotide polymorphisms (SNPs) (rs13387042 in the 2q35 region, rs17157903-RELN gene, rs2067980-MRPS30, rs2180341-RNF146, rs2981582-FGFR2, rs3803662-TOX3, rs3817198-LSP1, rs7696175-TLR1, rs889312-MAP3k1 and rs999737-RAD51L1) and risk of breast cancer in a combined sample of 7774 women (2956 NHW women from the US and 4694 Hispanic women from the US and Mexico) who participated in one of three population-based case-control studies of breast cancer. Genetic ancestry was estimated with a set of 104 ancestry-informative markers (AIMs) selected to discriminate between Indigenous American and European ancestry. 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 (low, intermediate, high).
Five of 10 SNPs were associated with breast cancer risk in this study. The associations with the FGFR2 and TOX3 variants were homogeneous across NHWs and Hispanics from all ancestry categories and the magnitude of the association in all women combined was similar to those previously reported. The other three variants were not associated with risk among NHWs, but in Hispanics statistically significant and heterogeneous associations were seen within the three categories of IA ancestry [2q35 per allele odds ratio (OR): 0.75 (95% CI = 0.50-1.15) for low IA ancestry, 1.19 (1.02-1.39) for intermediate IA ancestry, and 1.38 (1.04-1.82) for high IA ancestry, p interaction 0.02; RELN OR: 0.87 (0.59-1.29), 0.86 (0.72-1.04) and 1.69 (1.04-2.73), respectively, p interaction 0.03; TLR1 OR for risk allele homozygous: 0.74 (0.42-1.31), 1.39 (1.11-1.74) and 1.73 (1.19-2.52), respectively, p interaction 0.03].
Our results suggest that the degree of Indigenous American ancestry modifies the magnitude and direction of at least some of the previously reported variants associated with breast cancer risk. Genetic ancestry should be considered when assessing risk in women of mixed descent as well as for studies designed to discover causal mutations.
This abstract is also presented as Poster A62.
Citation Format: Laura Fejerman, Mariana C. Stern, Elad Ziv, Esther M. John, Gabriela Torres-Mejia, Lisa M. Hines, Roger Wolff, Wei Wang, Kathy Baumgartner, Anna Giuliano, Martha L. Slattery. Genetic susceptibility, genetic ancestry, and breast cancer risk among Hispanic and non-Hispanic white women. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr PR01.