A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese
A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese
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全基因组关联研究在汉族人群中发现了两个新的肺癌易感位点，分别位于13q12.12和22q12.2
DOI：
10.1038/ng.875
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发表时间：
2011-08-01
期刊：
影响因子：
30.8
通讯作者：
Shen, Hongbing
中科院分区：
文献类型：
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作者：
Hu, Zhibin;Wu, Chen;Shen, Hongbing
肺癌是全球癌症相关死亡的主要原因。为了确定改变中国血统个体肺癌风险的遗传因素，我们对5，408名受试者（2，331名肺癌患者（病例）和3，077名对照）进行了全基因组关联扫描，然后对12，722名受试者（6，313例病例和6，409名对照）进行了两阶段验证。综合分析确定了6个重复性良好的SNP，它们具有独立效应和显著的肺癌相关性。（P < 5.0 x 10（-8））位于TP 63（3q 28处的rs 4488809，P = 7.2 x 10（-26）），TERT-CLPTM 1 L（rs 465498和rs 2736100在5p15.33，P = 1.2 x 10（-20）和P = 1.0 x 10（-27）），MIPEP-TNFRSF 19（13q12.12处的rs753955，P = 1.5 × 10（-12））和MTMR 3-HORMAD 2-LIF（22q12.2处的rs 17728461和rs36600，分别为P = 1.1 × 10（-11）和P = 6.2 × 10（-13））。其中13q12.12和22q12.2两个基因座是中国人群中新发现的。这些结果提示，3q 28、5p15.33、13q12.12和22q12.2的遗传变异可能与中国汉族人肺癌的易感性有关。
Lung cancer is the leading cause of cancer-related deaths worldwide. To identify genetic factors that modify the risk of lung cancer in individuals of Chinese ancestry, we performed a genome-wide association scan in 5,408 subjects (2,331 individuals with lung cancer (cases) and 3,077 controls) followed by a two-stage validation among 12,722 subjects (6,313 cases and 6,409 controls). The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 x 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 x 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 x 10(-20) and P = 1.0 x 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 x 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 x 10(-11) and P = 6.2 x 10(-13), respectively). Two of these loci (13q12.12 and 22q12.2) were newly identified in the Chinese population. These results suggest that genetic variants in 3q28, 5p15.33, 13q12.12 and 22q12.2 may contribute to the susceptibility of lung cancer in Han Chinese.