Admixture mapping links RACGAP1 regulation to prostate cancer in African Americans

Abstract

Background/Aim: Prostate cancer is the most common malignancy in US males. African American men have higher incidence and mortality rates than European Americans. Five single nucleotide polymorphisms are associated with PCa. We hypothesized haplotypes inferred from these SNPs are also associated with PCa. Patients and Methods: We genotyped SNPs in a case-control admixture mapping study. SNP haplotypes inferred for 157 PCa cases and 150 controls were used in the regression analysis. Results: We found an association between “GTCCC”, “ATTCT”, and “ACCCC” haplotypes and PCa after ancestry adjustment (OR=3.62, 95%CI=1.42-9.21, p=0.0070; OR=7.89, 95%CI=2.36-26.31, p=0.0008; OR=4.34, 95%CI=1.75-10.78, p=0.0016). The rs615382 variant disrupts the recombination signal binding protein with immunoglobulin kappa J binding site in Rac GTPase activating protein 1 (RACGAP1). Conclusion: Disruption of notch 1 mediated-repression of RACGAP1 may contribute to PCa in African Americans.