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Title: Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women.
Authors: Wong JYY,  Zhang H,  Hsiung CA,  Shiraishi K,  Yu K,  Matsuo K,  Wong MP,  Hong YC,  Wang J,  Seow WJ,  Wang Z,  Song M,  Kim HN,  Chang IS,  Chatterjee N,  Hu W,  Wu C,  Mitsudomi T,  Zheng W,  Kim JH,  Seow A,  Caporaso NE,  Shin MH,  Chung LP,  An SJ,  Wang P,  Yang Y,  Zheng H,  Yatabe Y,  Zhang XC,  Kim YT,  Cai Q,  Yin Z,  Kim YC,  Bassig BA,  Chang J,  Ho JCM,  Ji BT,  Daigo Y,  Ito H,  Momozawa Y,  Ashikawa K,  Kamatani Y,  Honda T,  Hosgood HD,  Sakamoto H,  Kunitoh H,  Tsuta K,  Watanabe SI,  Kubo M,  Miyagi Y,  Nakayama H,  Matsumoto S,  Tsuboi M,  Goto K,  Shi J,  Song L,  Hua X,  Takahashi A,  Goto A,  Minamiya Y,  Shimizu K,  Tanaka K,  Wei F,  Matsuda F,  Su J,  Kim YH,  Oh IJ,  Song F,  Su WC,  Chen YM,  Chang GC,  Chen KY,  Huang MS,  Chien LH,  Xiang YB,  Park JY,  Kweon SS,  Chen CJ,  Lee KM,  Blechter B,  Li H,  Gao YT,  Qian B,  Lu D,  Liu J,  Jeon HS,  Hsiao CF,  Sung JS,  Tsai YH,  Jung YJ,  Guo H,  Hu Z,  Wang WC,  Chung CC,  Burdett L,  Yeager M,  Hutchinson A,  Berndt SI,  Wu W,  Pang H,  Li Y,  Choi JE,  Park KH,  Sung SW,  Liu L,  Kang CH,  Zhu M,  Chen CH,  Yang TY,  Xu J,  Guan P,  Tan W,  Wang CL,  Hsin M,  Sit KY,  Ho J,  Chen Y,  Choi YY,  Hung JY,  Kim JS,  Yoon HI,  Lin CC,  Park IK,  Xu P,  Wang Y,  He Q,  Perng RP,  Chen CY,  Vermeulen R,  Wu J,  Lim WY,  Chen KC,  Li YJ,  Li J,  Chen H,  Yu CJ,  Jin L,  Chen TY,  Jiang SS,  Liu J,  Yamaji T,  Hicks B,  Wyatt K,  Li SA,  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,  Chen Y,  Yang K,  Jiang G,  Fei K,  Wu G,  Lin HC,  Chen HL,  Fang YH,  Tsai FY,  Hsieh WS,  Yu J,  Stevens VL,  Laird-Offringa IA,  Marconett CN,  Rieswijk L,  Chao A,  Yang PC,  Shu XO,  Wu T,  Wu YL,  Lin D,  Chen K,  Zhou B,  Huang YC,  Kohno T,  Shen H,  Chanock SJ,  Rothman N,  Lan Q
Journal: Genomics
Date: 2020 Mar
Branches: BB, CGR, OD, OEEB, TDRP
PubMed ID: 31306748
PMC ID: PMC6954985
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.