Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry
Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry
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DOI：
10.1093/carcin/bgs093
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发表时间：
2012-04-01
期刊：
影响因子：
4.7
通讯作者：
Olopade, Olufunmilayo I.
中科院分区：
文献类型：
--
作者：
Huo, Dezheng;Zheng, Yonglan;Olopade, Olufunmilayo I.
使用针对欧洲血统人群优化的阵列芯片，在欧洲和亚洲血统人群的全基因组关联研究 (GWAS) 中确定了多个乳腺癌易感位点。检查这些基因座是否与非洲血统女性的乳腺癌风险相关非常重要。我们在乳腺癌病例对照研究中评估了 19 个位点的 25 个单核苷酸多态性 (SNP)，其中包括 1509 例病例和 1383 例对照。在尼日利亚、巴巴多斯和美国登记了病例和对照；所有妇女都有非洲血统。我们发现三个 SNP 之间存在显着关联，这些关联与之前针对非洲血统女性的精细绘图研究中报告的方向相同且程度相似。等位基因优势比为 1.24 [95% 置信区间 (CI)：1.04-1.47； P = 0.018] 对于 rs2981578-G 等位基因 (10q26/FGFR2)，对于 rs9397435-G 等位基因 (6q25) 为 1.34 (95% CI: 1.10-1.63; P = 0.0035)，对于 rs9397435-G 等位基因 (6q25) 为 1.34 (95% CI: 1.00-1.25; P = 0.0035) 0.04) 对于 rs3104793-C 等位基因 (16q12)。尽管观察到附加指数 SNP (rs3817198) 存在显着关联，但其方向与之前的 GWAS 研究相反。总之，这项研究强调了在不同种族/族裔群体中应用当前 GWAS 研究结果的复杂性，因为 GWAS 确定的索引 SNP 都无法在非洲血统的女性中复制。需要对非洲血统女性进行进一步的精细绘图研究，以揭示乳腺癌的其他致病变异。
Multiple breast cancer susceptibility loci have been identified in genome-wide association studies (GWAS) in populations of European and Asian ancestry using array chips optimized for populations of European ancestry. It is important to examine whether these loci are associated with breast cancer risk in women of African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19 loci in a pooled case-control study of breast cancer, which included 1509 cases and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the USA; all women were of African ancestry. We found significant associations for three SNPs, which were in the same direction and of similar magnitude as those reported in previous fine-mapping studies in women of African ancestry. The allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04-1.47; P = 0.018] for the rs2981578-G allele (10q26/FGFR2), 1.34 (95% CI: 1.10-1.63; P = 0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00-1.25; P = 0.04) for the rs3104793-C allele (16q12). Although a significant association was observed for an additional index SNP (rs3817198), it was in the opposite direction to prior GWAS studies. In conclusion, this study highlights the complexity of applying current GWAS findings across racial/ethnic groups, as none of GWAS-identified index SNPs could be replicated in women of African ancestry. Further fine-mapping studies in women of African ancestry will be needed to reveal additional and causal variants for breast cancer.