Genome-wide association study identifies new prostate cancer susceptibility loci
Genome-wide association study identifies new prostate cancer susceptibility loci
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DOI：
10.1093/hmg/ddr295
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发表时间：
2011-10-01
影响因子：
3.5
通讯作者：
Kraft, Peter
中科院分区：
文献类型：
--
作者：
Schumacher, Fredrick R.;Berndt, Sonja I.;Kraft, Peter
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原因，但对其病因和影响临床结果的因素知之甚少。 PrCa 的全基因组关联研究 (GWAS) 已确定至少 30 个与风险差异较小的不同位点相关。我们对 2782 例晚期 PrCa 病例（格里森分级 >= 8 级或肿瘤 C/D 期）和 4458 例对照（具有 571 243 个单核苷酸多态性 (SNP)）进行了 GWAS。基于两个已发表的 GWAS（包含 7358 例 PrCa 病例和 6732 例对照）中 4679 个 SNP（第 1 阶段，P < 0.02）的计算机复制，我们确定了与 2q37.3 处总体 PrCa 风险相关的新易感位点（rs2292884，P = 4.3 x 10(-8)）。我们还确认了早期 GWAS 所建议的 12q13 位点（rs902774，P = 8.6 x 10(-9)）。这些位点的估计每等位基因比值比（rs2292884 为 1.14，rs902774 为 1.17）在高级和非高级 PrCa 之间没有差异（异质性的仅病例检验分别为 P = 0.72 和 P = 0.61）。需要进一步的研究来评估这些或其他基因座是否与 PrCa 亚型存在差异相关。
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 x 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P = 8.6 x 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.