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

Wei Jie Seow, Keitaro Matsuo, Chao Agnes Hsiung, Kouya Shiraishi, Minsun Song, Hee NamKim, Maria Pik Wong, Yun Chul Hong, H. Dean Hosgood, Zhaoming Wang, I. Shou Chang, Jiu Cun Wang, Nilanjan Chatterjee, Margaret Tucker, Hu Wei, Tetsuya Mitsudomi, Wei Zheng, Jin Hee Kim, Baosen Zhou, Neil E. CaporasoDemetrius Albanes, Min Ho Shin, Lap Ping Chung, She Juan An, Ping Wang, Hong Zheng, Yasushi Yatabe, Xu Chao Zhang, Young Tae Kim, Xiao Ou Shu, Young Chul Kim, Bryan A. Bassig, Jiang Chang, James Chung Man Ho, Bu Tian Ji, Michiaki Kubo, Yataro Daigo, Hidemi Ito, Yukihide Momozawa, Kyota Ashikawa, Yoichiro Kamatani, Takayuki Honda, Hiromi Sakamoto, Hideo Kunitoh, Koji Tsuta, Shun Ichi Watanabe, Hiroshi Nokihara, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Masahiro Tsuboi, Koichi Goto, Zhihua Yin, Jianxin Shi, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Kimihiro Shimizu, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Jason Y.Y. Wong, Fumihiko Matsuda, Jian Su, Yeul Hong Kim, In Jae Oh, Fengju Song, Victor Ho Fun Lee, Wu Chou Su, Yuh Min Chen, Gee Chen Chang, Kuan Yu Chen, Ming Shyan Huang, Pan Chyr Yang, Hsien Chih Lin, Yong Bing Xiang, Adeline Seow, Jae Yong Park, Sun Seog Kweon, Chien Jen Chen, Haixin Li, Yu Tang Gao, Chen Wu, Biyun Qian, Daru Lu, Jianjun Liu, Hyo Sung Jeon, Chin Fu Hsiao, Jae Sook Sung, Ying Huang Tsai, Yoo Jin Jung, Huan Guo, Zhibin Hu, Wen Chang Wang, Charles C. Chung, Charles Lawrence, Laurie Burdett, Meredith Yeager, Kevin B. Jacobs, Amy Hutchinson, Sonja I. Berndt, Xingzhou He, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Lingmin Hu, Chung Hsing Chen, Tsung Ying Yang, Jun Xu, Peng Guan, Wen Tan, Chih Liang Wang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jen Yu Hung, Jun Suk Kim, Ho Il Yoon, Qiuyin Cai, Chien Chung Lin, In Kyu Park, Ping Xu, Jing Dong, Christopher Kim, Qincheng He, Reury Perng Perng, Chih Yi Chen, Roel Vermeulen, Junjie Wu, Wei Yen Lim, Kun Chieh Chen, John K.C. Chan, Minjie Chu, Yao Jen Li, Jihua Li, Hongyan Chen, Chong Jen Yu, Li Jin, Yen Li Lo, Ying Hsiang Chen, Joseph F. Fraumeni, Jie Liu, Taiki Yamaji, Yang Yang, Belynda Hicks, Kathleen Wyatt, Shengchao A. Li, Juncheng Dai, Hongxia Ma, Guangfu Jin, Bao Song, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ping Cui, Motoki Iwasaki, Taichi Shimazu, Shoichiro Tsugane, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Li Hsin Chien, Hui Ling Chen, Yu Chun Su, Fang Yu Tsai, Yi Song Chen, Jinming Yu, Victoria L. Stevens, Ite A. Laird-Offringa, Crystal N. Marconett, Dongxin Lin, Kexin Chen, Yi Long Wu, Maria Teresa Landi, Hongbing Shen, Nathaniel Rothman, Takashi Kohno, Stephen J. Chanock, Qing Lan

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

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 × 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.

Original languageEnglish
Pages (from-to)454-465
Number of pages12
JournalHuman molecular genetics
Volume26
Issue number2
DOIs
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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