Genetic Variants at 6p21.1 and 7p15.3 Are Associated with Risk of Multiple Cancers in Han Chinese
Genetic Variants at 6p21.1 and 7p15.3 Are Associated with Risk of Multiple Cancers in Han Chinese
复制标题
6p21.1 和 7p15.3 的遗传变异与中国汉族患多种癌症的风险相关
DOI：
10.1016/j.ajhg.2012.09.009
复制
发表时间：
2012-11-02
影响因子：
9.8
通讯作者：
Shen, Hongbing
中科院分区：
文献类型：
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作者：
Jin, Guangfu;Ma, Hongxia;Shen, Hongbing
在已报道的全基因组关联研究中发现的癌症易感基因通常是肿瘤特异性的；然而，也观察到了一些基因/基因座具有多效性的证据，并且在生物学上是可信的。我们假设基因组中有一些重要区域含有与多种癌症风险相关的基因变异。在目前的研究中，我们试图使用我们现有的肺癌、非贲门癌和食道鳞状细胞癌的全基因组扫描数据，绘制对多种癌症的风险具有一致影响的基因变异图，总共5368例病例和4006名对照(GWAS期)，然后对另外9001名患有这些癌症类型之一的病例和11436名对照进行进一步评估(复制阶段)。在复制阶段，进一步评估了5个满足多效性标准的变异体，其p值从1.10×10(-8)到8.96×10(-6)，用于三种癌症类型的全基因组扫描。我们发现位于6p21.1的rs2494938和位于7p15.3的rs2285947与这三种癌症在GWA期和复制期的相关性一致。在GWA期和复制期的联合样本中，rs2494938和rs2285947的等位基因与癌症风险的增加显著相关(优势比[OR]=1.15，95%可信区间[CI]，1.10~1.19和OR=1.17，95%CI，1.12~1.21)，p值分别为1.20×10(-12)和1.26×10(-16)，处于全基因组显著水平。我们的发现强调了6p21.1和7p15.3的变异在多种癌症易感性中的潜在重要性。
Cancer susceptibility loci identified in reported genome-wide association studies (GWAS) are often tumor-specific; however, evidence of pleiotropy of some genes/loci has also been observed and biologically plausible. We hypothesized that there are important regions in the genome harboring genetic variants associated with risk of multiple types of cancer. In the current study, we attempted to map genetic variants that have consistent effects on risk of multiple cancers using our existing genome-wide scan data of lung cancer, non-cardia gastric cancer, and esophageal squamous-cell carcinoma with overall 5,368 cases and 4,006 controls (GWAS stage), followed by a further evaluation in additional 9,001 cases with one of these cancer types and 11,436 controls (replication stage). Five variants satisfying the criteria of pleiotropy with p values from 1.10 x 10(-8) to 8.96 x 10(-6) for genome-wide scans of three cancer types were further evaluated in the replication stage. We found consistent associations of rs2494938 at 6p21.1 and rs2285947 at 7p15.3 with these three cancers in both GWAS and replication stages. In combined samples of GWAS and replication stages, the minor alleles of rs2494938 and rs2285947 were significantly associated with an increased risk of the cancers (odds ratio [OR] = 1.15, 95% confidence interval [CI], 1.10-1.19 and OR = 1.17, 95% CI, 1.12-1.21), with the p values being 1.20 x 10(-12) and 1.26 x 10(-16), respectively, which are at a genome-wide significance level. Our findings highlight the potential importance of variants at 6p21.1 and 7p15.3 in the susceptibility to multiple cancers.