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.
[1]NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[2]Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan.
[3]Natl Canc Ctr, Div Genome Biol, Res Inst, Tokyo, Japan.
[4]Aichi Canc Ctr, Div Canc Epidemiol & Prevent, Res Inst, Nagoya, Aichi, Japan.
[5]Nagoya Univ, Dept Canc Epidemiol, Grad Sch Med, Nagoya, Aichi, Japan.
[6]Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Peoples R China.
[7]Seoul Natl Univ, Dept Prevent Med, Coll Med, Seoul, South Korea.
[8]Fudan Univ, Sch Life Sci, Minist Educ, Key Lab Contemporary Anthropol, Shanghai, Peoples R China.
[9]Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China.
[10]Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
[11]Leidos Biomed Res Inc, Canc Genom Res Lab, Gaithersburg, MD USA.
[12]St Jude Childrens Res Hosp, Dept Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[13]Sookmyung Womens Univ, Dept Stat, Seoul, South Korea.
[14]Chonnam Natl Univ, Dept Prevent Med, Med Sch, Gwangju, South Korea.
[15]Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan, Taiwan.
[16]Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[17]Chinese Acad Med Sci & Peking Union Med Coll, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing, Peoples R China.
[18]Chinese Acad Med Sci & Peking Union Med Coll, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing, Peoples R China.
[19]Kinki Univ, Div Thorac Surg, Sch Med, Sayama, Osaka, Japan.
[20]Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, Nashville, TN USA.
[21]Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[22]Sejong Univ, Dept Integrat Biosci & Biotechnol, Seoul, South Korea.
[23]Guangdong Acad Med Sci, Guangdong Gen Hosp, Med Res Ctr, Guangdong Lung Canc Inst, Guangzhou, Peoples R China.
[24]Guangdong Acad Med Sci, Guangdong Gen Hosp, Canc Ctr, Guangzhou, Peoples R China.
[25]Tianjin Med Univ, Natl Clin Res Ctr Canc, Dept Radiotherapy, Key Lab Canc Prevent & Therapy,Canc Inst & Hosp, Tianjin, Peoples R China.
[26]Shanghai Pulm Hosp, Shanghai, Peoples R China.
[27]Tianjin Med Univ, Dept Epidemiol & Biostat, Canc Inst & Hosp, Tianjin, Peoples R China.
[28]Aichi Canc Ctr, Dept Pathol & Mol Diagnost, Cent Hosp, Nagoya, Aichi, Japan.
[29]Seoul Natl Univ, Canc Res Inst, Dept Thorac & Cardiovasc Surg, Coll Med, Seoul, South Korea.
[30]China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang, Peoples R China.
[31]Chonnam Natl Univ, Hwasun Eup, Lung & Esophageal Canc Clin, Hwasun Eup, South Korea.
[32]Chonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South Korea.
[33]Univ Hong Kong, Queen Mary Hosp, Dept Med, Pokfulam Rd, Hong Kong, Peoples R China.
[34]Shiga Univ Med Sci, Dept Med Oncol, Otsu, Shiga, Japan.
[35]Shiga Univ Med Sci, Canc Ctr, Otsu, Shiga, Japan.
[36]Univ Tokyo, Res Hosp, Ctr Antibody & Vaccine Therapy, Inst Med Sci, Tokyo, Japan.
[37]Aichi Canc Ctr, Div Canc Informat & Control, Res Inst, Nagoya, Aichi, Japan.
[38]Nagoya Univ, Dept Descript Canc Epidemiol, Grad Sch Med, Nagoya, Aichi, Japan.
[39]RIKEN, Lab Genotyping Dev, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
[40]RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan.
[41]Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[42]Natl Canc Ctr, Div Genet, Res Inst, Tokyo, Japan.
[43]Japanese Red Cross Med Ctr, Dept Med Oncol, Tokyo, Japan.
[44]Kansai Med Univ, Dept Pathol & Lab Med, Osaka, Japan.
[45]Natl Canc Ctr, Div Thorac Surg, Tokyo, Japan.
[46]Kanagawa Canc Ctr, Mol Pathol & Genet Div, Res Inst, Yokohama, Kanagawa, Japan.
[47]Kanagawa Canc Ctr, Dept Thorac Surg, Yokohama, Kanagawa, Japan.
[48]Natl Canc Ctr, Exploratory Oncol Res & Clin Trial Ctr EPOC, Div Translat Res, Chiba, Japan.
[49]Natl Canc Ctr Hosp East, Dept Thorac Surg, Chiba, Japan.
[50]Natl Canc Ctr Hosp East, Dept Thorac Oncol, Chiba, Japan.
[51]Natl Cerebral & Cardiovasc Ctr, Res Inst, Dept Genom Med, Osaka, Japan.
[52]Akita Univ, Grad Sch Med, Dept Cellular & Organ Pathol, Akita, Japan.
[53]Akita Univ, Grad Sch Med, Dept Thorac Surg, Akita, Japan.
[54]Gunma Univ Hosp, Dept Integrat, Ctr Gen Surg, Gunma, Japan.
[55]China Natl Environm Monitoring Ctr, Beijing, Peoples R China.
[56]Kyoto Univ, Ctr Genom Med, Grad Sch Med, Kyoto, Japan.
[57]Korea Univ, Coll Med, Dept Internal Med, Div Oncol Hematol,Anam Hosp, Seoul, South Korea.
[58]Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Internal Med, Tainan, Taiwan.
[59]Taipei Vet Gen Hosp, Dept Chest Med, Taipei, Taiwan.
[60]Taipei Med Univ, Coll Med Sci & Technol, Taipei, Taiwan.
[61]Natl Yang Ming Univ, Fac Med, Sch Med, Taipei, Taiwan.
[62]Taichung Vet Gen Hosp, Dept Internal Med, Div Chest Med, Taichung, Taiwan.
[63]Natl Taiwan Univ, Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan.
[64]Natl Taiwan Univ, Coll Med, Taipei, Taiwan.
[65]I Shou Univ, E Da Canc Hosp, Sch Med, Dept Internal Med, Kaohsiung, Taiwan.
[66]Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst,Sch Med, State Key Lab Oncogene & Related Genes, Shanghai, Peoples R China.
[67]Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, Dept Epidemiol,Sch Med, Shanghai, Peoples R China.
[68]Kyungpook Natl Univ, Lung Canc Ctr, Med Ctr, Daegu, South Korea.
[69]Chonnam Natl Univ, Jeonnam Reg Canc Ctr, Hwasun Hosp, Hwasun Eup, South Korea.
[70]Acad Sinica, Genom Res Ctr, Taipei, Taiwan.
[71]Korea Natl Open Univ, Dept Environm Hlth, Seoul, South Korea.
[72]Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[73]Genome Inst Singapore, Dept Human Genet, Singapore, Singapore.
[74]Anhui Med Univ, Sch Life Sci, Hefei, Peoples R China.
[75]Kyungpook Natl Univ, Canc Res Ctr, Med Ctr, Daegu, South Korea.
[76]Chiayi Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Chiayi, Taiwan.
[77]Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Occupat & Environm Hlth, Wuhan, Peoples R China.
[78]Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Minist Educ,Key Lab Environm & Hlth, Wuhan, Peoples R China.
[79]Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Epidemiol, Nanjing, Peoples R China.
[80]Taipei Med Univ, Coll Med Sci & Technol, PhD Program Translat Med, Taipei, Taiwan.
[81]Univ Hong Kong, Sch BioMed Sci, Hong Kong, Peoples R China.
[82]Canc Prevent Inst Calif, Fremont, CA USA.
[83]Catholic Univ Korea, Seoul St Marys Hosp, Dept Thorac & Cardiovasc Surg, Seoul, South Korea.
[84]Huazhong Univ Sci & Technol, Union Hosp, Canc Ctr, Dept Oncol, Wuhan, Peoples R China.
[85]Univ Hong Kong, Li Ka Shing LKS Fac Med, Sch Publ Hlth, Hong Kong, Peoples R China.
[86]Univ Liaoning Prov, Key Lab Canc Etiol & Intervent, Shenyang, Peoples R China.
[87]Chang Gung Mem Hosp, Dept Pulm & Crit Care, Taoyuan, Taiwan.
[88]Univ Hong Kong, Queen Mary Hosp, Dept Cardiothorac Surg, Hong Kong, Peoples R China.
[89]Univ Hong Kong, Dept Med, Hong Kong, Peoples R China.
[90]Korea Univ, Coll Med, Dept Internal Med, Div Med Oncol,Guro Hosp, Seoul, South Korea.
[91]Seoul Natl Univ, Dept Internal Med, Bundang Hosp, Seongnam, South Korea.
[92]Wuhan Iron & Steel Corp, Dept Oncol, Staff Worker Hosp, Wuhan, Peoples R China.
[93]Taipei Vet Gen Hosp, Chest Dept, Taipei, Taiwan.
[94]Chung Shan Med Univ, Inst Med, Taichung, Taiwan.
[95]Chung Shan Med Univ Hosp, Dept Surg, Div Thorac Surg, Taichung, Taiwan.
[96]Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Utrecht, Netherlands.
[97]Agcy Integrated Care, Singapore, Singapore.
[98]Qujing Ctr Dis Control & Prevent, Sanjiangdadao, Qujing, Peoples R China.
[99]Natl Taiwan Univ, Dept Internal Med, Coll Med, Taipei, Taiwan.
[100]Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Dept Oncol, Jinan, Peoples R China.
[101]Natl Canc Ctr, Ctr Publ Hlth Sci, Epidemiol & Prevent Grp, Tokyo, Japan.
[102]Kunming Med Univ, Yunnan Canc Hosp, Yunnan Canc Ctr, Dept Thorac Surg,Affiliated Hosp 3, Kunming, Yunnan, Peoples R China.
[103]Amer Canc Soc, Behav & Epidemiol Res Grp, Atlanta, GA 30329 USA.
[104]Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Surg,Dept Biochem & Mol Med, Los Angeles, CA 90007 USA.
[105]Univ Calif Berkeley, Sch Publ Hlth, Environm Hlth Sci Div, Berkeley, CA 94720 USA.
[106]NCI, Ctr Global Hlth, Bethesda, MD 20892 USA.
[107]Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Peoples R China.
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