African American-preponderant single nucleotide polymorphisms (SNPs) and risk of breast cancer

Abstract

Background: African American women more often present with more aggressive types of breast cancer than Caucasian women, but little is known whether genetic polymorphisms specific to or disproportionate in African Americans are associated with their risk of breast cancer.

Methods: A population-based case-control study was conducted including 194 cases identified through the Metropolitan Detroit Cancer Surveillance System and 189 controls recruited through random digit dialing to examine polymorphisms in genes involved in estrogen metabolism and action.

Results: The African American-specific CYP1A1 5639C allele was associated with an increased risk of breast cancer (odds ratio (OR)=2.34, 95% confidence interval (CI) 1.23-4.44) and this association with the CYP1A1 5639 locus was dependent on another polymorphism in the CYP3A4 gene (P=0.043 for the interaction). In addition, African American-predominant CYP1B1 432 Val allele was significantly more often found in the cases than in the controls overall and the HSD17B1 312 Gly allele was specifically associated with premenopausal breast cancer risk (OR=3.00, 95%CI 1.29-6.99).

Conclusion: These observations need to be confirmed in larger studies due to the limited statistical power of the study based on a small number of cases.

Fig. 1

Representative Taqman plots for the seven SNPs studied. There are 3 clusters, indicating wild type of homozygotes, heterozygotes, and minor allele homozygotes. A: CYP1A1 rs4986884, B: CYP1A1 rs4646903, C: CYP1B1 rs1056836, D: CYP3A4 rs2740574, E: CYP17A1 rs743572, F: HSD17B1 rs605059, and G: ER Beta rs1256059. See Table 1 for details of each SNP.