Genetic Risks for Breast Cancer in African American Women: Analysis of Candidate Single Nucleotide Polymorphisms from Association Studies.
Authors: Rajagopal P. , Fackenthal J. , Huo D. , Niu Q. , Zhang J. , Kirchhoff T. , Offit K. , Olopade O. 
Published: December 2010

Background: African American breast cancer patients present with more aggressive disease than Caucasian women. They are also more likely to experience earlier onset of illness and tumors that are resistant to current treatment options due to their high grade and negative hormone receptor status. These attributes are correlated with greater mortality. The different frequencies of these indicators in African American and Caucasian patients have been associated with genetic susceptibility and genetically driven progression of breast cancer. However, these studies have focused on well-known breast cancer genes, not the low-penetrance mutations identified by genome-wide association studies (GWAS).Aims: This pilot case-control replication study investigated both the overall and attribute-based breast cancer risk of African American women associated with three single nucleotide polymorphisms (SNPs) selected through previously published association studies, including a genome-wide association study by Gold et al. (2008), and predicted high odds ratios and high minor allele frequencies in the African American population compared to the original study populations. We hypothesized that rs2180341 and rs7776136, located in 6q22.33 and associated with risk in a GWAS of Ashkenazi Jewish familial breast cancer cases, would contribute to overall risk in a case-control cohort of African American women. We also hypothesized that rs3741378, a SNP in SIPA1 previously associated with hormone-receptor negative tumors, would contribute to this outcome in the same cohort. These SNPs were additionally studied for relevance to other clinical outcomes.Methods: Two hundred and eighteen cases and 105 controls from the University of Chicago Cancer Risk Clinic were genotyped for these three SNPs using SNaPshot multiplex. Clinical information, including age of diagnosis, family history, hormone receptor status, survival, and tumor grade and stage, was also collected. Statistical analysis was performed using Pearson's χ2 test, Fisher's exact test, logistic regression and supplementary tests in Stata.Results: Unlike other populations, the African American population showed allelic odds ratios of approximately 1.0 for all SNPs tested, indicating no statistically significant association between these SNPs and breast cancer risk. We also found no association with age of diagnosis, hormone receptor status, tumor stage and grade. However, the minor allele of rs2180341 was associated with decreased survival in patients with a hazard ratio of 3.991 (p=0.044, 95% CI: 1.038-15.337) for the homozygous minor allele genotype.Conclusion: This pilot study represents one of the first forays into the translation of breast cancer GWAS results to populations of African ancestry. Based on our preliminary findings, future studies on a larger cohort of breast cancer cases of African ancestry will be needed to identify risk factors that may be particular to this patient population.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3068.