Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations

Seow W.J.,Matsuo K.,Hsiung C.A.,Shiraishi K., Song M., NamKim H.,Wong M.P.,Hong Y.-C.,Dean Hosgood H., III,Wang Z.,Chang I.-S., Wang J.-C.,Chatterjee N.,Tucker M., Wei H.,Mitsudomi T.,Zheng W.,Kim J.H.,Zhou B.,Caporaso N.E.,Albanes D.,Shin M.-H.,Chung L.P.,An S.-J.,Wang P.,Zheng H.,Yatabe Y.,Zhang X.-C.,Kim Y.T.,Shu X.-O.,Kim Y.-C.,Bassig B.A.,Chang J.,Man Ho J.C., Ji B.-T., Kubo M.,Daigo Y.,Ito H.,Momozawa Y.,Ashikawa K.,Kamatani Y.,Honda T., Sakamoto H.,Kunitoh H., Tsuta K.,Watanabe S.-I., Nokihara H.,Miyagi Y.,Nakayama H.,Matsumoto S.,Tsuboi M.,Goto K., Yin Z.,Shi J.,Takahashi A.,Goto A.,Minamiya Y., Shimizu K.,Tanaka K.,Wu T., Wei F.,Wong J.Y.Y., Matsuda F.,Su J.,Kim Y.H.,Oh I.-J.,Song F.,Lee V.H.F.,Su W.-C.,Chen Y.-M., Chang G.-C.,Chen K.-Y., Huang M.-S.,Yang P.-C.,Lin H.-C.,Xiang Y.-B.,Seow A.,Park J.Y.,Kweon S.-S.,Chen C.-J., Li H., Gao Y.-T.,Wu C., Qian B.,Lu D.,Liu J.,Jeon H.-S.,Hsiao C.-F.,Sung J.S., Tsai Y.-H., Jung Y.J.,Guo H., Hu Z., Wang W.-C.,Chung C.C.,Lawrence C.,Burdett L.,Yeager M.,Jacobs K.B.,Hutchinson A.,Berndt S.I., He X., Wu W., Wang J.,Li Y.,Choi J.E.,Park K.H.,Sung S.W.,Liu L.,Kang C.H., Hu L.,Chen C.-H.,Yang T.-Y., Xu J., Guan P.,Tan W.,Wang C.-L.,Loon Sihoe A.D.,Chen Y.,Choi Y.Y., Hung J.-Y.,Kim J.S., Yoon H.-I., Cai Q.,Lin C.-C., Park I.K., Xu P.,Dong J.,Kim C.,He Q., Perng R.-P.,Chen C.-Y., Vermeulen R.,Wu J.,Lim W.-Y.,Chen K.-C., Chan J.K., Chu M.,Li Y.-J.,Li J.,Chen H.,Yu C.-J.,Jin L.,Lo Y.-L.,Chen Y.-H.,Fraumeni J.F., Jr,Liu J.,Yamaji T.,Yang Y.,Hicks B., Wyatt K., Li S.A.,Dai J., Ma H., Jin G., Song B.,Wang Z.,Cheng S., Li X., Ren Y.,Cui P., Iwasaki M.,Shimazu T.,Tsugane S., Zhu J., Jiang G., Fei K., Wu G.,Chien L.-H.,Chen H.-L., Su Y.-C.,Tsai F.-Y.,Chen Y.-S.,Yu J.,Stevens V.L., Laird-Offringa I.A.,Marconett C.N.,Lin D.,Chen K.,Wu Y.-L.,Landi M.T.,Shen H.,Rothman N.,Kohno T.,Chanock S.J.,Lan Q.

HUMAN MOLECULAR GENETICS（2017）

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摘要

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 X 10(-8)), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications.

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