Evaluating genetic risk for prostate cancer among Japanese and Latinos.
Evaluating genetic risk for prostate cancer among Japanese and Latinos.
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DOI：
10.1158/1055-9965.epi-12-0598
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发表时间：
2012-11
期刊：
影响因子：
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通讯作者：
Haiman CA
中科院分区：
文献类型：
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作者：
Cheng I;Chen GK;Nakagawa H;He J;Wan P;Laurie CC;Shen J;Sheng X;Pooler LC;Crenshaw AT;Mirel DB;Takahashi A;Kubo M;Nakamura Y;Al Olama AA;Benlloch S;Donovan JL;Guy M;Hamdy FC;Kote-Jarai Z;Neal DE;Wilkens LR;Monroe KR;Stram DO;Muir K;Eeles RA;Easton DF;Kolonel LN;Henderson BE;Le Marchand L;Haiman CA
不同人群中前列腺癌的全基因组关联研究（GWAS）很少。为了寻找新的前列腺癌风险变异，我们对日本人和拉丁美洲人的前列腺癌进行了GWAS。此外，我们测试了前列腺癌的风险变异，并建立了日本人和拉丁美洲人前列腺癌的遗传风险模型。我们的第一阶段前列腺癌GWAS包括来自多种族队列的日本人（病例/对照=1,033/1,042）和拉丁美洲人（病例/对照=1,043/1,057）。在日本（病例/对照=1,583/3,386）和欧洲（病例/对照=1,854/1,894）前列腺癌（2期）的GWAS中，从1期（P < 1.0×10−4）开始的显著相关性进行了计算机检测。在已知风险区域之外，没有新的1期snp具有全基因组意义。对于日本人来说，在第一阶段，最显著的新关联出现了10个snp （P<8.0）。X10−6)在染色体2q33；然而，在第二阶段没有重复这种情况。对于拉丁美洲人来说，在已知的3p12风险位点上，与rs17023900的相关性最为显著（阶段1:OR=1.45； P=7.01×10−5；阶段2:OR=1.58； P= 3.05×10−7）。在日本人和拉丁美洲人（一期）中，大多数已确定的前列腺癌风险变异（79%和88%）分别与前列腺癌呈正相关。这些变异的累积效应显著影响前列腺癌风险（每个等位基因的OR= 1.10; P = 2.71×10 - 25和OR=1.07; P = 1.02×10 - 16，分别为日本人和拉丁美洲人）。我们的前列腺癌GWAS没有发现新的全基因组显著变异。然而，我们的研究结果表明，既定的前列腺癌风险变异对日本人和拉丁美洲人的风险有显著影响。
There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Our first stage GWAS of prostate cancer included Japanese (cases/controls=1,033/1,042) and Latino (cases/controls=1,043/1,057) from the Multiethnic Cohort. Significant associations from stage 1 (P < 1.0×10−4) were examined in silico in GWAS of prostate cancer (stage 2) in Japanese (cases/controls=1,583/3,386) and Europeans (cases/controls=1,854/1,894). No novel stage 1 SNPs outside of known risk regions reached genome-wide significance. For Japanese, in stage 1, the most notable putative novel association was seen with 10 SNPs (P<8.0. x10−6) at chromosome 2q33; however, this was not replicated in stage 2. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage 1: OR=1.45; P=7.01×10−5 and stage 2: OR=1.58; P =3.05×10−7). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele=1.10; P = 2.71×10−25 and OR=1.07; P = 1.02×10−16 for Japanese and Latinos, respectively). Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings demonstrate that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos.