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

Li J

Wong JYY(1), Zhang H(2), Hsiung CA(3), Shiraishi K(4), Yu K(2), Matsuo K(5), Wong MP(6), Hong YC(7), Wang J(8), Seow WJ(9), Wang Z(10), Song M(11), Kim HN(12), Chang IS(13), Chatterjee N(14), Hu W(2), Wu C(15), Mitsudomi T(16), Zheng W(17), Kim JH(18), Seow A(9), Caporaso NE(2), Shin MH(12), Chung LP(6), An SJ(19), Wang P(20), Yang Y(21), Zheng H(22), Yatabe Y(23), Zhang XC(19), Kim YT(24), Cai Q(17), Yin Z(25), Kim YC(26), Bassig BA(2), Chang J(15), Ho JCM(27), Ji BT(2), Daigo Y(28), Ito H(29), Momozawa Y(30), Ashikawa K(30), Kamatani Y(31), Honda T(4), Hosgood HD(32), Sakamoto H(33), Kunitoh H(34), Tsuta K(35), Watanabe SI(36), Kubo M(30), Miyagi Y(37), Nakayama H(38), Matsumoto S(39), Tsuboi M(40), Goto K(41), Shi J(2), Song L(2), Hua X(2), Takahashi A(42), Goto A(43), Minamiya Y(44), Shimizu K(45), Tanaka K(45), Wei F(46), Matsuda F(47), Su J(19), Kim YH(48), Oh IJ(26), Song F(22), Su WC(49), Chen YM(50), Chang GC(51), Chen KY(52), Huang MS(53), Chien LH(13), Xiang YB(54), Park JY(55), Kweon SS(56), Chen CJ(57), Lee KM(58), Blechter B(59), Li H(22), Gao YT(60), Qian B(22), Lu D(8), Liu J(61), Jeon HS(62), Hsiao CF(3), Sung JS(48), Tsai YH(63), Jung YJ(24), Guo H(64), Hu Z(65), Wang WC(66), Chung CC(67), Burdett L(67), Yeager M(67), Hutchinson A(67), Berndt SI(2), Wu W(25), Pang H(68), Li Y(69), Choi JE(62), Park KH(48), Sung SW(70), Liu L(71), Kang CH(24), Zhu M(65), Chen CH(3), Yang TY(72), Xu J(73), Guan P(74), Tan W(15), Wang CL(75), Hsin M(76), Sit KY(76), Ho J(77), Chen Y(9), Choi YY(62), Hung JY(53), Kim JS(78), Yoon HI(79), Lin CC(49), Park IK(24), Xu P(80), Wang Y(65), He Q(25), Perng RP(81), Chen CY(82), Vermeulen R(83), Wu J(8), Lim WY(84), Chen KC(72), Li YJ(57), Li J(85), Chen H(8), Yu CJ(86), Jin L(8), Chen TY(3), Jiang SS(13), Liu J(87), Yamaji T(88), Hicks B(67), Wyatt K(67), Li SA(67), Dai J(65), Ma H(65), Jin G(65), Song B(87), Wang Z(87), Cheng S(87), Li X(74), Ren Y(74), Cui P(22), Iwasaki M(88), Shimazu T(88), Tsugane S(88), Zhu J(21), Chen Y(89), Yang K(89), Jiang G(21), Fei K(21), Wu G(46), Lin HC(3), Chen HL(3), Fang YH(3), Tsai FY(13), Hsieh WS(3), Yu J(87), Stevens VL(90), Laird-Offringa IA(91), Marconett CN(91), Rieswijk L(92), Chao A(93), Yang PC(52), Shu XO(17), Wu T(64), Wu YL(19), Lin D(15), Chen K(22), Zhou B(25), Huang YC(89), Kohno T(4), Shen H(94), Chanock SJ(2), Rothman N(2), Lan Q(2).
Author information:
(1)Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Electronic address: [Email]
(2)Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
(3)Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
(4)Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
(5)Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan; Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
(6)Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
(7)Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
(8)Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
(9)Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
(10)Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc, Gaithersburg, MD, USA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
(11)Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Department of Statistics, Sookmyung Women's University, Seoul, Republic of Korea.
(12)Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
(13)National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
(14)Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
(15)Department of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
(16)Division of Thoracic Surgery, Kinki University School of Medicine, Sayama, Japan.
(17)Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
(18)Department of Integrative Bioscience & Biotechnology, Sejong University, Seoul, Republic of Korea.
(19)Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
(20)Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
(21)Shanghai Pulmonary Hospital, Shanghai, China.
(22)Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
(23)Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Central Hospital, Nagoya, Japan.
(24)Department of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
(25)Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.
(26)Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-eup, Republic of Korea; Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
(27)Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong.
(28)Department of Medical Oncology and Cancer Center, Shiga University of Medical Science, Otsu, Japan; Center for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
(29)Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan; Department of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
(30)Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
(31)Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
(32)Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
(33)Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
(34)Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.
(35)Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka, Japan.
(36)Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
(37)Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Kanagawa, Japan.
(38)Department of Thoracic Surgery, Kanagawa Cancer Center, Kanagawa, Japan.
(39)Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center
(EPOC), National Cancer Center, Chiba, Japan.
(40)Department of Thoracic Surgery, National Cancer Center Hospital East, Chiba, Japan.
(41)Department of Thoracic Oncology, National Cancer Center Hospital East, Japan.
(42)Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
(43)Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita City, Japan.
(44)Department of Thoracic Surgery, Graduate School of Medicine, Akita University, Akita City, Japan.
(45)Department of Integrative Center of General Surgery, Gunma University Hospital, Gunma, Japan.
(46)China National Environmental Monitoring Center, Beijing, China.
(47)Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
(48)Department of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea.
(49)Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
(50)Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
(51)School of Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
(52)Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
(53)Department of Internal Medicine, E-Da Cancer Hospital, School of Medicine, I-Shou University, Kaohsiung, Taiwan.
(54)State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
(55)Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
(56)Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea; Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun-eup, Republic of Korea.
(57)Genomic Research Center, Academia Sinica, Taipei, Taiwan.
(58)Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Department of Environmental Health, Korea National Open University, Seoul, Republic of Korea.
(59)Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
(60)Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
(61)Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Department of Human Genetics, Genome Institute of Singapore, Singapore; School of Life Sciences, Anhui Medical University, Hefei, China.
(62)Cancer Research Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
(63)Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
(64)Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
(65)Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
(66)The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
(67)Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc, Gaithersburg, MD, USA.
(68)School of BioMedical Sciences, The University of Hong Kong, Hong Kong.
(69)Cancer Prevention Institute of California, Fremont, CA, USA.
(70)Department of Thoracic and Cardiovascular Surgery, Seoul St Mary's Hospital, The Catholic University of Korea, Republic of Korea.
(71)Department of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
(72)Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
(73)School of Public Health, Li Ka Shing
(LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
(74)Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China; Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang, China.
(75)Department of Pulmonary and Critical Care, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
(76)Department of Cardiothoracic Surgery, Queen Mary Hospital, The University of Hong Kong, China.
(77)Department of Medicine, The University of Hong Kong, China.
(78)Division of Medical Oncology, Department of Internal Medicine, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea.
(79)Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
(80)Department of Oncology, Wuhan Iron and Steel Corporation Staff Worker Hospital, Wuhan, China.
(81)Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan.
(82)Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Thoracic Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.
(83)Division of Environmental Epidemiology, Institute for Risk Assessment Sciences
(IRAS), Utrecht University, Utrecht, the Netherlands.
(84)Agency for Integrated Care, Singapore.
(85)Qujing Center for Diseases Control and Prevention, Sanjiangdadao, Qujing, China.
(86)Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
(87)Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China.
(88)Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
(89)Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, China.
(90)Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA.
(91)Department of Surgery, Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
(92)Environmental Health Sciences Division, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
(93)Center for Global Health, National Cancer Institute, Bethesda, MD, USA.
(94)Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

https://dx.doi.org/10.1016/j.ygeno.2019.07.008

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.