Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women

Jason Y.Y. Wong, Han Zhang, Chao A. Hsiung, Kouya Shiraishi, Kai Yu, Keitaro Matsuo, Maria Pik Wong, Yun Chul Hong, Jiucun Wang, Wei Jie Seow, Zhaoming Wang, Minsun Song, Hee Nam Kim, I. Shou Chang, Nilanjan Chatterjee, Wei Hu, Chen Wu, Tetsuya Mitsudomi, Wei Zheng, Jin Hee KimAdeline Seow, Neil E. Caporaso, Min Ho Shin, Lap Ping Chung, She Juan An, Ping Wang, Yang Yang, Hong Zheng, Yasushi Yatabe, Xu Chao Zhang, Young Tae Kim, Qiuyin Cai, Zhihua Yin, Young Chul Kim, Bryan A. Bassig, Jiang Chang, James Chung Man Ho, Bu Tian Ji, Yataro Daigo, Hidemi Ito, Yukihide Momozawa, Kyota Ashikawa, Yoichiro Kamatani, Takayuki Honda, H. Dean Hosgood, Hiromi Sakamoto, Hideo Kunitoh, Koji Tsuta, Shun ichi Watanabe, Michiaki Kubo, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Masahiro Tsuboi, Koichi Goto, Jianxin Shi, Lei Song, Xing Hua, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Kimihiro Shimizu, Kazumi Tanaka, Fusheng Wei, Fumihiko Matsuda, Jian Su, Yeul Hong Kim, In Jae Oh, Fengju Song, Wu Chou Su, Yu Min Chen, Gee Chen Chang, Kuan Yu Chen, Ming Shyan Huang, Li Hsin Chien, Yong Bing Xiang, Jae Yong Park, Sun Seog Kweon, Chien Jen Chen, Kyoung Mu Lee, Batel Blechter, Haixin Li, Yu Tang Gao, 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, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Sonja I. Berndt, Wei Wu, Herbert Pang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, C. H. Kang, Meng Zhu, Chung Hsing Chen, Tsung Ying Yang, Jun Xu, Peng Guan, Wen Tan, Chih Liang Wang, Michael Hsin, Ko Yung Sit, James Ho, Ying Chen, Yi Young Choi, Jen Yu Hung, Jun Suk Kim, Ho Il Yoon, Chien Chung Lin, In Kyu Park, Ping Xu, Yuzhuo Wang, Qincheng He, Reury Perng Perng, Chih Yi Chen, Roel Vermeulen, Junjie Wu, Wei Yen Lim, Kun Chieh Chen, Yao Jen Li, Jihua Li, Hongyan Chen, Chong Jen Yu, Li Jin, Tzu Yu Chen, Shih Sheng Jiang, Jie Liu, Taiki Yamaji, 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, Kaiyun Yang, Gening Jiang, Ke Fei, Guoping Wu, Hsien Chin Lin, Hui Ling Chen, Yao Huei Fang, Fang Yu Tsai, Wan Shan Hsieh, Jinming Yu, Victoria L. Stevens, Ite A. Laird-Offringa, Crystal N. Marconett, Linda Rieswijk, Ann Chao, Pan Chyr Yang, Xiao Ou Shu, Tangchun Wu, Y. L. Wu, Dongxin Lin, Kexin Chen, Baosen Zhou, Yun Chao Huang, Takashi Kohno, Hongbing Shen, Stephen J. Chanock, Nathaniel Rothman, Qing Lan

    Research output: Contribution to journalArticlepeer-review

    14 Citations (Scopus)

    Abstract

    We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

    Original languageEnglish
    Pages (from-to)1223-1232
    Number of pages10
    JournalGenomics
    Volume112
    Issue number2
    DOIs
    Publication statusPublished - 2020 Mar

    Bibliographical note

    Publisher Copyright:
    © 2019

    Keywords

    • Lung adenocarcinoma
    • Lung cancer
    • Mendelian randomization
    • Pathway analysis
    • Tuberculosis

    ASJC Scopus subject areas

    • Genetics

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