Authors' Affiliations: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; Department of Family Medicine and Public Health Sciences and Barbara Ann Karmanos Institute, Wayne State University School of Medicine, Detroit, Michigan; and Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada.
Cancer Epidemiol Biomarkers Prev. 2014 Jan;23(1):209-14. doi: 10.1158/1055-9965.EPI-13-0818. Epub 2013 Nov 12.
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 (AA), who experience a higher incidence of RCC. We conducted a GWAS in which we analyzed 1,136,723 common single-nucleotide polymorphisms (SNP) among 255 cases and 375 controls of African ancestry, and further investigated 16 SNPs in a replication set (140 cases and 543 controls). The 12p11.23 variant rs10771279, located 77 kb 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 [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 clear-cell RCC is novel and requires additional investigation. Additional investigation of rs10771279 and other suggestive GWAS findings is also needed.
全基因组关联研究（GWAS）在欧洲血统的人群中发现了四个肾细胞癌（RCC）易感性位点。尚未在非裔美国人（AA）中进行 GWAS，因为他们的 RCC 发病率更高。我们进行了一项 GWAS，其中分析了 255 例非洲裔病例和 375 例对照中的 1136723 个常见单核苷酸多态性（SNP），并在复制组中进一步研究了 16 个 SNP（140 例病例和 543 例对照）。位于欧洲血统 RCC 标记 rs718314 77 kb 处的 12p11.23 变体 rs10771279 与 GWAS 中的 RCC 风险相关（P = 1.2×10(-7)) ，但未复制（P = 0.99）。与欧洲血统的发现一致，11q13.3 上的 rs7105934 的 A 等位基因与降低的风险相关[OR，0.76，95%置信区间（CI），0.64-0.91；P = 0.0022]。该等位基因的频率高于欧洲血统 GWAS 中观察到的频率（对照分别为 0.56 和 0.07）。rs7105934 与透明细胞 RCC（ccRCC：OR，0.56；P = 7.4×10(-7)) 更强相关，而与其他或未知组织学的病例无关（OR，1.02；P = 0.86）。对来自这些研究的欧洲血统参与者中 rs7105934 的亚型分析得出了类似的发现（ORs 分别为 0.69 和 0.92）。这项研究提供了，据我们所知，rs7105934 是 AA 中 RCC 易感性位点的第一个证据。我们发现，与该 SNP 的关联可能仅适用于透明细胞 RCC，这是新颖的，需要进一步研究。还需要进一步研究 rs10771279 和其他提示性 GWAS 结果。
