Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women
Publication date
2020-03
Authors
Wong, J.Y.Y.
Hsiung, C.A.
Matsuo, K.
Wong, M.P.
Seow, W.J.
Song, M.
Chang, I.-S.
Chatterjee, N.
Hu, W.
Wu, C.
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Supervisors
Document Type
Article
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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.
Keywords
Tuberculosis, Lung cancer, Lung adenocarcinoma, Mendelian randomization, Pathway analysis, SDG 3 - Good Health and Well-being
Citation
Wong, J Y Y, Hsiung, C A, Matsuo, K, Wong, M P, Seow, W J, Song, M, Chang, I-S, Chatterjee, N, Hu, W, Wu, C, Mitsudomi, T, Zheng, W, Kim, J H, Seow, A, Caporaso, N E, Shin, M-H, Chung, L P, An, S-J, Zheng, H, Yatabe, Y, Kim, Y T, Cai, Q, Kim, Y-C, Bassig, B A, Ho, J C M, Ji, B-T, Daigo, Y, Ito, H, Momozawa, Y, Ashikawa, K, Kamatani, Y, Honda, T, Hosgood, H D, Sakamoto, H, Kunitoh, H, Tsuta, K, Watanabe, S-I, Kubo, M, Miyagi, Y, Nakayama, H, Matsumoto, S, Tsuboi, M, Goto, K, Song, L, Hua, X, Takahashi, A, Goto, A, Minamiya, Y, Shimizu, K, Tanaka, K, Wei, F, Matsuda, F, Kim, Y H, Oh, I-J, Song, F, Su, W-C, Chang, G-C, Chen, K-Y, Chien, L-H, Xiang, Y-B, Kweon, S-S, Lee, K-M, Blechter, B, Qian, B, Lu, D, Jeon, H-S, Hsiao, C-F, Sung, J S, Tsai, Y-H, Jung, Y J, Chung, C C, Burdett, L, Yeager, M, Hutchinson, A, Berndt, S I, Pang, H, Choi, J E, Park, K H, Sung, S W, Zhu, M, Guan, P, Tan, W, Hsin, M, Sit, K-Y, Ho, J, Choi, Y Y, Kim, J S, Yoon, H I, Park, I K, Xu, P, He, Q, Perng, R-P, Vermeulen, R, Lim, W-Y, Chen, K-C, Jin, L, Jiang, S-S, Yamaji, T, Hicks, B, Wyatt, K, Dai, J, Jin, G, Song, B, Cheng, S, Cui, P, Iwasaki, M, Shimazu, T, Tsugane, S, Fei, K, Wu, G, Lin, H-C, Fang, Y-H, Tsai, F-Y, Hsieh, W-S, Yu, J, Stevens, V L, Laird-Offringa, I A, Marconett, C N, Rieswijk, L, Chao, A, Shu, X-O, Lin, D, Chen, K, Zhou, B, Kohno, T, Shen, H, Chanock, S J, Rothman, N & Lan, Q 2020, 'Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women', Genomics, vol. 112, no. 2, pp. 1223-1232. https://doi.org/10.1016/j.ygeno.2019.07.008