Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Hum Mol Genet. 2011 Oct 1;20(19):3867-75. doi: 10.1093/hmg/ddr295. Epub 2011 Jul 8.
Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.
前列腺癌（PrCa）是发达国家男性中最常见的非皮肤癌，也是癌症死亡的第二大主要原因，但对于其病因和影响临床结果的因素知之甚少。前列腺癌的全基因组关联研究（GWAS）已经确定了至少 30 个与风险微小差异相关的不同位点。我们在 2782 例晚期前列腺癌病例（Gleason 分级≥8 或肿瘤分期 C/D）和 4458 例对照中进行了 GWAS，其中包含 571243 个单核苷酸多态性（SNP）。基于对 4679 个 SNP 的计算机模拟复制（阶段 1，P < 0.02），这些 SNP 来自两个已发表的包含 7358 例前列腺癌病例和 6732 例对照的 GWAS，我们在 2q37.3 上确定了一个与整体前列腺癌风险相关的新易感位点（rs2292884，P=4.3×10(-8)）。我们还证实了一个在早期 GWAS 中提示的位于 12q13 的位点（rs902774，P=8.6×10(-9)）。这些位点的每个等位基因的估计比值比（rs2292884 为 1.14，rs902774 为 1.17）在晚期和非晚期前列腺癌之间没有差异（用于异质性的病例仅检验 P=0.72 和 P=0.61）。需要进一步的研究来评估这些或其他位点是否与前列腺癌亚型有差异关联。
