A genome-wide association study of renal cell carcinoma among African Americans.
A genome-wide association study of renal cell carcinoma among African Americans.
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DOI：
10.1158/1055-9965.epi-13-0818
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发表时间：
2014-01
期刊：
影响因子：
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通讯作者：
Chanock SJ
中科院分区：
文献类型：
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作者：
Purdue MP;Ye Y;Wang Z;Colt JS;Schwartz KL;Davis FG;Rothman N;Chow WH;Wu X;Chanock SJ
欧洲血统人群肾细胞癌（RCC）的全基因组关联研究（GWAS）已经确定了四个易感位点。非洲裔美国人（AAs）的RCC发病率较高，但没有进行GWAS。我们进行了GWAS，分析了255例非洲血统和375例对照的1,136,723个常见单核苷酸多态性（snp），并进一步研究了一个复制集（140例，543例对照）中的16个snp。12p11.23变异rs10771279位于欧洲血统RCC标记rs718314的77kb处，与GWAS患者的RCC风险相关（P=1.2 × 10−7），但没有重复（P=0.99）。与欧洲血统研究结果一致，11q13.3上rs7105934的A等位基因与风险降低相关[优势比(OR)=0.76, 95%可信区间(CI)= 0.64-0.91；P = 0.0022)。该等位基因的频率高于欧洲血统GWAS（对照组分别为0.56和0.07）。rs7105934的相关性在透明细胞RCC中更强（ccRCC: OR=0.56； P=7.4 × 10−7），而在其他或未知组织学的病例中不存在（OR=1.02； P=0.86）。对这些研究中欧洲血统参与者rs7105934亚型的分析得出了类似的结果（or分别为0.69和0.92）。据我们所知，本研究首次证明rs7105934是AAs中RCC易感位点。我们发现与这种SNP的关联可能是ccRCC特有的，这是新颖的，需要进一步的研究。还需要对rs10771279和其他提示性GWAS结果进行进一步调查。
Genome-wide association studies (GWAS) of renal cell carcinoma (RCC) in populations of European ancestry have identified four susceptibility loci. No GWAS has been conducted among African Americans (AAs), who experience a higher incidence of RCC. We conducted a GWAS in which we analyzed 1,136,723 common single-nucleotide polymorphisms (SNPs) among 255 cases and 375 controls of African ancestry, and further investigated 16 SNPs in a replication set (140 cases, 543 controls). The 12p11.23 variant rs10771279, located 77kb from the European-ancestry RCC marker rs718314, was associated with RCC risk in the GWAS (P=1.2 × 10−7) but did not replicate (P=0.99). Consistent with European-ancestry findings, the A allele of rs7105934 on 11q13.3 was associated with decreased risk [odds ratio (OR)=0.76, 95% confidence interval (CI)=0.64–0.91; P=0.0022]. The frequency of this allele was higher than that observed in the European-ancestry GWAS (0.56 and 0.07 respectively among controls). The rs7105934 association was stronger for clear cell RCC (ccRCC: OR=0.56; P=7.4 × 10−7) and absent for cases of other or unknown histology (OR=1.02; P=0.86). Analyses of rs7105934 by subtype among European-ancestry participants from these studies yielded similar findings (ORs 0.69 and 0.92 respectively). This study provides, to our knowledge, the first evidence that rs7105934 is an RCC susceptibility locus among AAs. Our finding that the association with this SNP may be specific to ccRCC is novel and requires additional investigation. Additional investigation of rs10771279 and other suggestive GWAS findings is also needed.