Prostate cancer in African-American men and polymorphism in the calcium-sensing receptor

Background: Prospective epidemiologic studies indicate that the risk for advanced prostate cancer is increased among men with high levels of serum calcium. Because serum calcium levels are influenced by the calcium-sensing receptor (CaSR), we examined prostate cancer in African-American men in relation to three single nucleotide polymorphisms (SNPs) in the CaSR gene, A986S, R990G and Q1011E. This is the first study of CaSR polymorphisms and risk of prostate cancer. Results: The CaSR genotypes were not associated with prostate cancer overall. However, we observed significant heterogeneity by disease stage for the Q1011E polymorphism (p = 0.02). Advanced cases were significantly less likely than controls or localized cases to be homozygous for the minor allele of the Q1011E polymorphism (1 vs. 5%). Cases with advanced disease were six times less likely to carry two copies of the minor allele than were controls (OR = 0.16, p = 0.02) or localized cases (OR = 0.15, p = 0.01) and were significantly older at diagnosis (68.8 +/- 5.7 vs. 64.0 +/- 9.0 y for the QQ and EE genotypes, p = 0.004). Methods: We genotyped three CaSR SNPs for 458 African-American prostate cancer cases and 248 controls from a population-based case-control study, the California Collaborative Prostate Cancer Study. Conclusions: The CaSR Q1011E minor allele, which is common in populations with African ancestry, may be associated with a less aggressive form of prostate cancer among African-American men.