Prostate cancer risk allele specific for African descent associates with pathologic stage at prostatectomy

Abstract

Purpose: A region on chromosome 8q24 was recently identified as a novel prostate cancer risk locus. Inherited variation in this region is associated with prostate cancer risk in the general population (21-58%), and specific alleles show a strong association in African-American men. This study was designed to evaluate associations between 8q24 risk alleles and clinical variables, such as pathologic stage, age at diagnosis, and recurrence, in a case series of African-American men.

Experimental design: Peripheral blood DNA samples from 114 African-American men with prostate cancer, including 106 who had undergone radical prostatectomy, were genotyped for six single-nucleotide polymorphisms on three 8q24 regions. The presence of these single-nucleotide polymorphisms was compared with clinicopathologic and follow-up data after radical prostatectomy.

Results: The mean age of diagnosis and follow-up time were 57.4 (+/-8.9) years and 49.1 (+/-31.6) months, respectively. Patients carrying the Broad11934905 A risk allele, which is specific for African ancestry, were more likely to have a higher pathologic stage (pT(3-4)) than individuals with the wild type (odds ratio, 4.48; 95% confidence interval, 1.42-14.14; P = 0.011). A trend toward increased frequency of and shorter time to biochemical recurrence was noted in patients with this risk allele on Kaplan-Meier unadjusted survival analysis (P = 0.076).

Conclusions: The Broad11934905 polymorphism at 8q24, which is only found in people of African ancestry, is associated with an increase in non-organ-confined prostate cancer at prostatectomy. In addition, for those with this risk allele, there is a trend toward early biochemical recurrence that requires validation in larger studies.

Figure 1.

Kaplan-Meier prostate-specific antigen recurrence-free survival curves with and without the risk allele at the Broad11934905 locus of 8q24. GG, wild type; AG, risk allele.

Figure 2.

Association between the number of at-risk genotypes in region 2 and age at diagnosis. For each single-nucleotide polymorphism in region 2, the number of at-risk genotypes was counted. For example, in Rs6983561, wherein the risk allele is C, AA is 0; CA, 1; and CC, 2. Then, the number of all at-risk genotypes in region 2 were added up. Although not significant, a trend is observed toward earlier age at diagnosis with more at-risk genotypes.