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全基因组关联研究在日本人群中鉴定出前列腺癌的五个新易感位点。

Genome-wide association study identifies five new susceptibility loci for prostate cancer in the Japanese population.

机构信息

Laboratory for Biomarker Development, Center of Genomic Medicine, RIKEN, Tokyo, Japan.

出版信息

Nat Genet. 2010 Sep;42(9):751-4. doi: 10.1038/ng.635. Epub 2010 Aug 1.

Abstract

Prostate cancer is one of the most common malignancies in males throughout the world, and its incidence is increasing in Asian countries. We carried out a genome-wide association study and replication study using 4,584 Japanese men with prostate cancer and 8,801 control subjects. From the thirty-one associated SNPs reported in previous genome-wide association studies in European populations, we confirmed the association of nine SNPs at P < 1.0 x 10(-7) and ten SNPs at P < 0.05 in the Japanese population. The remaining 12 SNPs showed no association (P > 0.05). In addition, we report here five new loci for prostate cancer susceptibility, at 5p15 (lambda-corrected probability P(GC) = 3.9 x 10(-18)), GPRC6A/RFX6 (P(GC) = 1.6 x 10(-12)), 13q22 (P(GC) = 2.8 x 10(-9)), C2orf43 (P(GC) = 7.5 x 10(-8)) and FOXP4 (P(GC) = 7.6 x 10(-8)). These findings advance our understanding of the genetic basis of prostate carcinogenesis and also highlight the genetic heterogeneity of prostate cancer susceptibility among different ethnic populations.

摘要

前列腺癌是全世界男性中最常见的恶性肿瘤之一,其在亚洲国家的发病率正在上升。我们对 4584 名日本男性前列腺癌患者和 8801 名对照者进行了全基因组关联研究和复制研究。在欧洲人群先前的全基因组关联研究中报道的 31 个相关 SNP 中,我们在日本人群中证实了 9 个 SNP 的关联(P<1.0x10(-7))和 10 个 SNP 的关联(P<0.05)。其余 12 个 SNP 没有关联(P>0.05)。此外,我们在这里报告了五个新的前列腺癌易感性位点,位于 5p15(lambda 校正概率 P(GC)=3.9x10(-18))、GPRC6A/RFX6(P(GC)=1.6x10(-12))、13q22(P(GC)=2.8x10(-9))、C2orf43(P(GC)=7.5x10(-8))和 FOXP4(P(GC)=7.6x10(-8))。这些发现增进了我们对前列腺癌发生遗传基础的理解,也突出了不同种族人群中前列腺癌易感性的遗传异质性。

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