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, Linda Rieswijk

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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
Early online date12 Jul 2019
DOIs
Publication statusPublished - Mar 2020

Keywords

  • APOPTOSIS
  • CANCER SUSCEPTIBILITY LOCI
  • DISEASE
  • Lung adenocarcinoma
  • Lung cancer
  • MEN
  • Mendelian randomization
  • PULMONARY TUBERCULOSIS
  • Pathway analysis
  • RISK
  • SMOKERS
  • Tuberculosis
  • VARIANTS

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