Abstract
Recent admixture mapping and linkage/association studies have implicated an approximately 1 Mb region on chromosome 8q24 in prostate cancer susceptibility. In a subsequent follow-up investigation, Haiman et al. (Nat Genet 2007;39:638-44) observed significant, independent associations between 7 markers within this region and sporadic prostate cancer risk in a multi-ethnic sample. To clarify the risk associated with hereditary prostate cancer, we tested for prostate cancer association with 6 of these 7 markers in a sample of 1,015 non-Hispanic white men with and without prostate cancer from 403 familial and early-onset prostate cancer families. Single nucleotide polymorphisms (SNPs) rs6983561 and rs6983267 showed the strongest evidence of prostate cancer association. Using a family-based association test, the minor ("C") allele of rs6983561 and the major ("G") allele of rs6983267 were preferentially transmitted to affected men (p < 0.05), with estimated odds ratios (ORs) of 2.26 (95% confidence interval of 1.06-4.83) and 1.30 (95% confidence interval of 0.99-1.71), respectively, for an additive model. Notably, rs6983561 was significantly associated with prostate cancer among men diagnosed at an early (<50 years) but not later age (p = 0.03 versus p = 0.21). Similarly, the association with rs6983267 was (not) statistically significant among men with(out) clinically aggressive disease (p = 0.007 versus p = 0.34). Our results confirm the association of prostate cancer with several of the SNPs on chromosome 8q24 initially reported by Haiman et al. In addition, our results suggest that the increased risk associated with these SNPs is approximately doubled in individuals predisposed to develop early onset or clinically aggressive disease.