We conducted a genome-wide association study of 3090 sporadic prostate cancer patients and controls using the Affymetrix 10 000 SNP GeneChip. Initial screening of 40 prostate cancer cases and 40 non-cancer controls revealed 237 SNPs to be associated with prostate cancer (P<0.05). Among these SNPs, 33 were selected for further association analysis of 2069 men who had undergone a cancer-screening prostate biopsy. Results identified five loci as being significantly associated with increased prostate cancer risk in this larger sample (rs 1930293, OR=1.7, P=0.03; rs 717809-2p12, OR=1.3, P=0.03; rs 494770-4q34, OR=1.3, P=0.01; rs 2348763-7p21, OR=1.5, P=0.01; rs 1552895-9p22, OR=1.5, P=0.002). To validate these association data, 61 additional HapMap tagSNPs spanning the latter five loci were genotyped in this subject cohort and an additional 1021 men (total subject number=3090). This analysis revealed tag SNP rs 4568789 (chromosome 1q25) and tag SNP rs 13225697 (chromosome 7p21) to be significantly associated with prostate cancer (P-values 0.009 and 0.008, respectively). Haplotype analysis revealed significant associations of prostate cancer with two allele risk haplotypes on both chromosome 1q25 (adjusted OR of 2.7 for prostate cancer, P=0.0003) and chromosome 7p21 (adjusted OR of 1.3, P=0.0004). As linkage data have identified a putative prostate cancer gene on chromosome 1q25 (HPC1), and microarray data have revealed the ETV1 oncogene to be overexpressed in prostate cancer tissue, it appears that chromosome 1q25 and 7p21 may be sites of gene variants conferring risk for sporadic and inherited forms of prostate cancer.