Replication and cumulative effects of GWAS-identified genetic variations for prostate cancer in Asians: a case-control study in the ChinaPCa consortium
Replication and cumulative effects of GWAS-identified genetic variations for prostate cancer in Asians: a case-control study in the ChinaPCa consortium
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亚洲人前列腺癌 GWAS 鉴定的遗传变异的复制和累积效应：ChinaPCa 联盟的病例对照研究
DOI：
10.1093/carcin/bgr279
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发表时间：
2012-02-01
期刊：
影响因子：
4.7
通讯作者：
Xu, Jianfeng
中科院分区：
文献类型：
--
作者：
Wang, Meilin;Liu, Fang;Xu, Jianfeng
最近的一项全基因组关联研究在日本人群中发现了五种新的前列腺癌易感性基因变异，但尚不清楚这些新发现的变异是否与包括中国男性在内的其他人群的前列腺癌风险有关。在一项病例对照研究中，我们对1524名前列腺癌患者和2169名来自中国前列腺癌遗传学联合会(ChinaPCA)的对照受试者进行了这五种突变的基因分型。我们发现5个基因变异中有3个与前列腺癌相关(5p15的rs12653946的P=4.33x10(-8)，6q22的rs339331的P=4.43x10(-5)，13q22的rs9600079的8.42x10(-4))。随着风险变异等位基因数目的增加，累积效应呈剂量依赖关系(P-趋势=2.58×10(-13))，携带5-6个风险等位基因的男性患前列腺癌的风险是携带0-2个风险等位基因的男性的2倍(优势比=2.26，95%可信区间=1.78-2.87)。此外，与C等位基因相比，rs339331T等位基因与RFX6和GPRC6A的高信使RNA表达显著相关。然而，这些变异与临床分期、Gleason评分或家族史无关。这些结果进一步证明，在日本男性中发现的风险基因也与中国男性的前列腺癌易感性有关。
A recent genome-wide association study has identified five new genetic variants for prostate cancer susceptibility in a Japanese population, but it is unknown whether these newly identified variants are associated with prostate cancer risk in other populations, including Chinese men. We genotyped these five variants in a case-control study of 1524 patients diagnosed with prostate cancer and 2169 control subjects from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). We found that three of the five genetic variants were associated with prostate cancer risk (P = 4.33 x 10(-8) for rs12653946 at 5p15, 4.43 x 10(-5) for rs339331 at 6q22 and 8.42 x 10(-4) for rs9600079 at 13q22, respectively). A cumulative effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P-trend = 2.58 x 10(-13)), and men with 5-6 risk alleles had a 2-fold higher risk of prostate cancer than men with 0-2 risk alleles (odds ratio = 2.26, 95% confidence interval = 1.78-2.87). Furthermore, rs339331 T allele was significantly associated with RFX6 and GPRC6A higher messenger RNA expression, compared with the C allele. However, none of the variants was associated with clinical stage, Gleason score or family history. These results provide further evidence that the risk loci identified in Japanese men also contribute to prostate cancer susceptibility in Chinese men.