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

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.

SUBMITTER: Wong JYY

PROVIDER: S-EPMC6954985 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Wong Jason Y Y JYY Zhang Han H Hsiung Chao A CA Shiraishi Kouya K Yu Kai K Matsuo Keitaro K Wong Maria Pik MP Hong Yun-Chul YC Wang Jiucun J Seow Wei Jie WJ Wang Zhaoming Z Song Minsun M Kim Hee Nam HN Chang I-Shou IS Chatterjee Nilanjan N Hu Wei W Wu Chen C Mitsudomi Tetsuya T Zheng Wei W Kim Jin Hee JH Seow Adeline A Caporaso Neil E NE Shin Min-Ho MH Chung Lap Ping LP An She-Juan SJ Wang Ping P Yang Yang Y Zheng Hong H Yatabe Yasushi Y Zhang Xu-Chao XC Kim Young Tae YT Cai Qiuyin Q Yin Zhihua Z Kim Young-Chul YC Bassig Bryan A BA Chang Jiang J Ho James Chung Man JCM Ji Bu-Tian BT Daigo Yataro Y Ito Hidemi H Momozawa Yukihide Y Ashikawa Kyota K Kamatani Yoichiro Y Honda Takayuki T Hosgood H Dean HD Sakamoto Hiromi H Kunitoh Hideo H Tsuta Koji K Watanabe Shun-Ichi SI Kubo Michiaki M Miyagi Yohei Y Nakayama Haruhiko H Matsumoto Shingo S Tsuboi Masahiro M Goto Koichi K Shi Jianxin J Song Lei L Hua Xing X Takahashi Atsushi A Goto Akiteru A Minamiya Yoshihiro Y Shimizu Kimihiro K Tanaka Kazumi K Wei Fusheng F Matsuda Fumihiko F Su Jian J Kim Yeul Hong YH Oh In-Jae IJ Song Fengju F Su Wu-Chou WC Chen Yu-Min YM Chang Gee-Chen GC Chen Kuan-Yu KY Huang Ming-Shyan MS Chien Li-Hsin LH Xiang Yong-Bing YB Park Jae Yong JY Kweon Sun-Seog SS Chen Chien-Jen CJ Lee Kyoung-Mu KM Blechter Batel B Li Haixin H Gao Yu-Tang YT Qian Biyun B Lu Daru D Liu Jianjun J Jeon Hyo-Sung HS Hsiao Chin-Fu CF Sung Jae Sook JS Tsai Ying-Huang YH Jung Yoo Jin YJ Guo Huan H Hu Zhibin Z Wang Wen-Chang WC Chung Charles C CC Burdett Laurie L Yeager Meredith M Hutchinson Amy A Berndt Sonja I SI Wu Wei W Pang Herbert H Li Yuqing Y Choi Jin Eun JE Park Kyong Hwa KH Sung Sook Whan SW Liu Li L Kang C H CH Zhu Meng M Chen Chung-Hsing CH Yang Tsung-Ying TY Xu Jun J Guan Peng P Tan Wen W Wang Chih-Liang CL Hsin Michael M Sit Ko-Yung KY Ho James J Chen Ying Y Choi Yi Young YY Hung Jen-Yu JY Kim Jun Suk JS Yoon Ho Il HI Lin Chien-Chung CC Park In Kyu IK Xu Ping P Wang Yuzhuo Y He Qincheng Q Perng Reury-Perng RP Chen Chih-Yi CY Vermeulen Roel R Wu Junjie J Lim Wei-Yen WY Chen Kun-Chieh KC Li Yao-Jen YJ Li Jihua J Chen Hongyan H Yu Chong-Jen CJ Jin Li L Chen Tzu-Yu TY Jiang Shih-Sheng SS Liu Jie J Yamaji Taiki T Hicks Belynda B Wyatt Kathleen K Li Shengchao A SA Dai Juncheng J Ma Hongxia H Jin Guangfu G Song Bao B Wang Zhehai Z Cheng Sensen S Li Xuelian X Ren Yangwu Y Cui Ping P Iwasaki Motoki M Shimazu Taichi T Tsugane Shoichiro S Zhu Junjie J Chen Ying Y Yang Kaiyun K Jiang Gening G Fei Ke K Wu Guoping G Lin Hsien-Chin HC Chen Hui-Ling HL Fang Yao-Huei YH Tsai Fang-Yu FY Hsieh Wan-Shan WS Yu Jinming J Stevens Victoria L VL Laird-Offringa Ite A IA Marconett Crystal N CN Rieswijk Linda L Chao Ann A Yang Pan-Chyr PC Shu Xiao-Ou XO Wu Tangchun T Wu Y L YL Lin Dongxin D Chen Kexin K Zhou Baosen B Huang Yun-Chao YC Kohno Takashi T Shen Hongbing H Chanock Stephen J SJ Rothman Nathaniel N Lan Qing Q

Genomics 20190712 2

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 conta ...[more]

PMID: 31306748

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Project description:PurposeWe aimed to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them.MethodsThe main data analysis used publicly available summary-level data from 2 large genome-wide association study consortia. Mendelian randomization (MR) analysis used 65 genetic variants derived from the Social Science Genetic Association Consortium as instrumental variables for years of schooling. The outcomes from the Breast Cancer Association Consortium (BCAC) were the overall breast cancer risk (122,977 cases/105,974 controls in women) and the two subtypes: estrogen receptor (ER)-positive breast cancer and ER-negative breast cancer. Fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods for sensitivity analyses.ResultsResults showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER-negative breast cancer (odds ratio, 0.73; 95% confidence interval, 0.64-0.84; p-value < 0.001). This finding was consistent with the results of the sensitivity analyses. Physical activities can help improve the protective effect of education against breast cancer, with relatively large mediation proportions. Education increases the risk of ER-positive breast cancer due to alterations in high-density lipoprotein level, triglyceride level, height, waist-to-hip ratio, body mass index, and smoking status, with relative medium mediation proportions. Other mediators including low-density lipoprotein, hip circumference, number of cigarettes smoked per day, time spent performing light physical activity, and performing vigorous physical activity for > 10 minutes explain a small part of the causal effect of education on the risk of developing breast cancer, and their mediation proportion is approximately 1%.ConclusionA low level of education is a causal risk factor in the development of breast cancer as it is associated with poor lipid profile, obesity, smoking, and types of physical activity.

Dataset Information

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

Publications

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

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