Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma.
Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma.
复制标题
人类白细胞抗原（HLA）Ⅱ类及其他基因座变异与表皮生长因子受体（EGFR）突变型肺腺癌易感性的关联
DOI：
10.1038/ncomms12451
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发表时间：
2016-08-09
影响因子：
16.6
通讯作者：
Kohno T
中科院分区：
文献类型：
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作者：
Shiraishi K;Okada Y;Takahashi A;Kamatani Y;Momozawa Y;Ashikawa K;Kunitoh H;Matsumoto S;Takano A;Shimizu K;Goto A;Tsuta K;Watanabe SI;Ohe Y;Watanabe Y;Goto Y;Nokihara H;Furuta K;Yoshida A;Goto K;Hishida T;Tsuboi M;Tsuchihara K;Miyagi Y;Nakayama H;Yokose T;Tanaka K;Nagashima T;Ohtaki Y;Maeda D;Imai K;Minamiya Y;Sakamoto H;Saito A;Shimada Y;Sunami K;Saito M;Inazawa J;Nakamura Y;Yoshida T;Yokota J;Matsuda F;Matsuo K;Daigo Y;Kubo M;Kohno T
由体细胞EGFR突变驱动的肺腺癌在东亚人（30-50%）中比在欧洲/美国人（10-20%）中更常见。在这里，我们通过在3，173例EGFR突变阳性肺腺癌日本患者和15，158例对照中进行全基因组关联研究，然后进行两项验证研究，调查这种疾病风险的遗传因素。4个基因座，5p15.33（TERT），6p21.3（BTNL 2），3q 28（TP 63）和17q24.2（BPTF），以前被证明与东亚人的总体肺腺癌风险密切相关，被重新发现为与EGFR突变阳性肺腺癌的易感性较高相关的基因座。此外，另外两个位点，HLA II类6p21.32（rs 2179920; P =5.1 × 10−17，每等位基因OR=1.36）和6p21.1（FOXP 4）（rs 2495239; P=3.9 × 10−9，每等位基因OR=1.19）被新确定为与EGFR突变阳性肺腺癌相关的位点。这项研究表明，多种遗传因素的风险与EGFR突变的肺腺癌。 与其他人群相比，肺腺癌中的EGFR突变在东亚人群中更常见。在这里，作者在EGFR突变型癌症中进行了全基因组关联研究，并确定了与发展这种分子亚型癌症风险相关的基因座。
Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30–50%) than in European/Americans (10–20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10−17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10−9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations. EGFR mutations in lung adenocarcinoma are more frequent in East Asians compared to other populations. Here, the authors carry out a genome-wide association study in EGFR mutant cancers and identify loci that are associated with risk of developing this molecular subtype of cancer.