Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia

Batel Blechter; Jason Y.Y. Wong; Chao Agnes Hsiung; H. Dean Hosgood; Zhihua Yin; Xiao Ou Shu; Han Zhang; Jianxin Shi; Lei Song; Minsun Song; Wei Zheng; Zhaoming Wang; Neil Caporaso; Laurie Burdette; Meredith Yeager; Sonja I. Berndt; Maria Teresa Landi; Chien Jen Chen; Gee Chen Chang; Chin Fu Hsiao; Ying Huang Tsai; Kuan Yu Chen; Ming Shyan Huang; Wu Chou Su; Yuh Min Chen; Li Hsin Chien; Chung Hsing Chen; Tsung Ying Yang; Chih Liang Wang; Jen Yu Hung; Chien Chung Lin; Reury Perng Perng; Chih Yi Chen; Kun Chieh Chen; Yao Jen Li; Chong Jen Yu; Yi Song Chen; Ying Hsiang Chen; Fang Yu Tsai; Wei Jie Seow; Bryan A. Bassig; Wei Hu; Bu Tian Ji; Wei Wu; Peng Guan; Qincheng He; Yu Tang Gao; Qiuyin Cai; Wong Ho Chow; Yong Bing Xiang; Dongxin Lin; Chen Wu; Yi Long Wu; Min Ho Shin; Yun Chul Hong; Keitaro Matsuo; Kexin Chen; Maria Pik Wong; Daru Lu; Li Jin; Jiu Cun Wang; Adeline Seow; Tangchun Wu; Hongbing Shen; Joseph F. Fraumeni; Pan Chyr Yang; I. Shou Chang; Baosen Zhou; Stephen J. Chanock; Nathaniel Rothman; Nilanjan Chatterjee; Qing Lan

doi:10.1016/j.envint.2020.105975

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia

Batel Blechter, Jason Y.Y. Wong, Chao Agnes Hsiung, H. Dean Hosgood, Zhihua Yin, Xiao Ou Shu, Han Zhang, Jianxin Shi, Lei Song, Minsun Song, Wei Zheng, Zhaoming Wang, Neil Caporaso, Laurie Burdette, Meredith Yeager, Sonja I. Berndt, Maria Teresa Landi, Chien Jen Chen, Gee Chen Chang, Chin Fu HsiaoYing Huang Tsai, Kuan Yu Chen, Ming Shyan Huang, Wu Chou Su, Yuh Min Chen, Li Hsin Chien, Chung Hsing Chen, Tsung Ying Yang, Chih Liang Wang, Jen Yu Hung, Chien Chung Lin, Reury Perng Perng, Chih Yi Chen, Kun Chieh Chen, Yao Jen Li, Chong Jen Yu, Yi Song Chen, Ying Hsiang Chen, Fang Yu Tsai, Wei Jie Seow, Bryan A. Bassig, Wei Hu, Bu Tian Ji, Wei Wu, Peng Guan, Qincheng He, Yu Tang Gao, Qiuyin Cai, Wong Ho Chow, Yong Bing Xiang, Dongxin Lin, Chen Wu, Yi Long Wu, Min Ho Shin, Yun Chul Hong, Keitaro Matsuo, Kexin Chen, Maria Pik Wong, Daru Lu, Li Jin, Jiu Cun Wang, Adeline Seow, Tangchun Wu, Hongbing Shen, Joseph F. Fraumeni, Pan Chyr Yang, I. Shou Chang, Baosen Zhou, Stephen J. Chanock, Nathaniel Rothman, Nilanjan Chatterjee, Qing Lan

Epidemiology & Population Health

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10⁻²⁶). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10⁻³). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

Original language	English (US)
Article number	105975
Journal	Environment international
Volume	147
DOIs	https://doi.org/10.1016/j.envint.2020.105975
State	Published - Feb 2021

Keywords

Gene-environment interaction
Household coal use
Lung adenocarcinoma
Never-smoking women in Asia
Polygenic risk score

ASJC Scopus subject areas

Environmental Science(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.envint.2020.105975

Cite this

Blechter, B., Wong, J. Y. Y., Agnes Hsiung, C., Hosgood, H. D., Yin, Z., Shu, X. O., Zhang, H., Shi, J., Song, L., Song, M., Zheng, W., Wang, Z., Caporaso, N., Burdette, L., Yeager, M., Berndt, S. I., Teresa Landi, M., Chen, C. J., Chang, G. C., ... Lan, Q. (2021). Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia. Environment international, 147, [105975]. https://doi.org/10.1016/j.envint.2020.105975

Blechter, B, Wong, JYY, Agnes Hsiung, C, Hosgood, HD, Yin, Z, Shu, XO, Zhang, H, Shi, J, Song, L, Song, M, Zheng, W, Wang, Z, Caporaso, N, Burdette, L, Yeager, M, Berndt, SI, Teresa Landi, M, Chen, CJ, Chang, GC, Hsiao, CF, Tsai, YH, Chen, KY, Huang, MS, Su, WC, Chen, YM, Chien, LH, Chen, CH, Yang, TY, Wang, CL, Hung, JY, Lin, CC, Perng, RP, Chen, CY, Chen, KC, Li, YJ, Yu, CJ, Chen, YS, Chen, YH, Tsai, FY, Jie Seow, W, Bassig, BA, Hu, W, Ji, BT, Wu, W, Guan, P, He, Q, Gao, YT, Cai, Q, Chow, WH, Xiang, YB, Lin, D, Wu, C, Wu, YL, Shin, MH, Hong, YC, Matsuo, K, Chen, K, Pik Wong, M, Lu, D, Jin, L, Wang, JC, Seow, A, Wu, T, Shen, H, Fraumeni, JF, Yang, PC, Chang, IS, Zhou, B, Chanock, SJ, Rothman, N, Chatterjee, N & Lan, Q 2021, 'Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia', Environment international, vol. 147, 105975. https://doi.org/10.1016/j.envint.2020.105975

@article{efdd91ca99d94930855a5aa3c05a8829,

title = "Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia",

abstract = "We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10−26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10−3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.",

keywords = "Gene-environment interaction, Household coal use, Lung adenocarcinoma, Never-smoking women in Asia, Polygenic risk score",

author = "Batel Blechter and Wong, {Jason Y.Y.} and {Agnes Hsiung}, Chao and Hosgood, {H. Dean} and Zhihua Yin and Shu, {Xiao Ou} and Han Zhang and Jianxin Shi and Lei Song and Minsun Song and Wei Zheng and Zhaoming Wang and Neil Caporaso and Laurie Burdette and Meredith Yeager and Berndt, {Sonja I.} and {Teresa Landi}, Maria and Chen, {Chien Jen} and Chang, {Gee Chen} and Hsiao, {Chin Fu} and Tsai, {Ying Huang} and Chen, {Kuan Yu} and Huang, {Ming Shyan} and Su, {Wu Chou} and Chen, {Yuh Min} and Chien, {Li Hsin} and Chen, {Chung Hsing} and Yang, {Tsung Ying} and Wang, {Chih Liang} and Hung, {Jen Yu} and Lin, {Chien Chung} and Perng, {Reury Perng} and Chen, {Chih Yi} and Chen, {Kun Chieh} and Li, {Yao Jen} and Yu, {Chong Jen} and Chen, {Yi Song} and Chen, {Ying Hsiang} and Tsai, {Fang Yu} and {Jie Seow}, Wei and Bassig, {Bryan A.} and Wei Hu and Ji, {Bu Tian} and Wei Wu and Peng Guan and Qincheng He and Gao, {Yu Tang} and Qiuyin Cai and Chow, {Wong Ho} and Xiang, {Yong Bing} and Dongxin Lin and Chen Wu and Wu, {Yi Long} and Shin, {Min Ho} and Hong, {Yun Chul} and Keitaro Matsuo and Kexin Chen and {Pik Wong}, Maria and Daru Lu and Li Jin and Wang, {Jiu Cun} and Adeline Seow and Tangchun Wu and Hongbing Shen and Fraumeni, {Joseph F.} and Yang, {Pan Chyr} and Chang, {I. Shou} and Baosen Zhou and Chanock, {Stephen J.} and Nathaniel Rothman and Nilanjan Chatterjee and Qing Lan",

note = "Funding Information: The FLCCA was supported in part by intramural funding from National Cancer Institute . Further funding was provided by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan , a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry Health, Labor and Welfare of Japan , by Health and Labor Sciences Research Grants for Research on Applying Health Technology from the Ministry of Health, Labor and Welfare of Japan , by the National Cancer Center Research and Development Fund, the National Research Foundation of Korea ( NRF ) grant funded by the Korea government ( MEST ) (grant No. 2011-0016106 ), a grant of the National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea ( A111218-11-GM04 ), the Program for Changjiang Scholars and Innovative Research Team in University in China (IRT_14R40 to K.C.), the National Science & Technology Pillar Program (2011BAI09B00), MOE 111 Project (B13016), the National Natural Science Foundation of China (No. 30772531 , and 81272618 ), Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine (No. 2012A061400006 ), Special Fund for Research in the Public Interest from the National Health and Family Planning Commission of PRC (No. 201402031 ), and the Ministry of Science and Technology, Taiwan ( MOST 103-2325-B-400-023 & 104-2325-B-400-012 ). The Japan Lung Cancer Study ( JLCS ) was supported in part by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development ( 15ck0106096h0002 ) and the Management Expenses Grants from the Government to the National Cancer Center (26-A-1) for Biobank. BioBank Japan was supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government. The Japan Public Health Center-based prospective Study (the JPHC Study) was supported by the National Cancer Center Research and Development Fund (23-A31[toku] and 26-A-2) (since 2011) and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010). The Taiwan GELAC Study (Genetic Epidemiological Study for Lung AdenoCarcinoma) was supported by grants from the National Research Program on Genomic Medicine in Taiwan (DOH99-TD-G-111-028), the National Research Program for Biopharmaceuticals in Taiwan (MOHW 103-TDUPB-211-144003, MOST 103-2325-B-400-023) and the Bioinformatics Core Facility for Translational Medicine and Biotechnology Development (MOST 104-2319-B-400-002). This work was also supported by the Jinan Science Research Project Foundation (201102051), the National Key Scientific and Technological Project (2011ZX09307-001-04), the National Natural Science Foundation of China (No.81272293), the State Key Program of National Natural Science of China (81230067), the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. NRF2014R1A2A2A05003665), Sookmyung Women{\textquoteright}s University Research Grants, Korea (1-1603-2048), Agency for Science, Technology and Research (A*STAR), Singapore and the US National Institute of Health Grant (1U19CA148127-01). The overall GWAS project was supported by the intramural program of the US National Institutes of Health/National Cancer Institute. The following is a list of grants by study center: SKLCS (Y.T.K.)—National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2011-0016106). (J.C.) – This work was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health &Welfare, Republic of Korea (grant no. 0720550-2). (J.S.S) – grant number is A010250. WLCS (T.W.)—National Key Basic Research and Development Program (2011CB503800). SLCS (B.Z.)—National Nature Science Foundation of China (81102194). Liaoning Provincial Department of Education (LS2010168). China Medical Board (00726). GDS (Y.L.W.)—Foundation of Guangdong Science and Technology Department (2006B60101010, 2007A032000002, 2011A030400010). Guangzhou Science and Information Technology Bureau (2011Y2-00014). Chinese Lung Cancer Research Foundation, National Natural Science Foundation of China (81101549). Natural Science Foundation of Guangdong Province (S2011010000792). TLCS (K.C., B.Q)—Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT), China (IRT1076). Tianjin Cancer Institute and Hospital. National Foundation for Cancer Research (US). FLCS (J.C.W., D.R., L.J.)—Ministry of Health (201002007). Ministry of Science and Technology (2011BAI09B00). National S&T Major Special Project (2011ZX09102-010-01). China National High-Tech Research and Development Program (2012AA02A517, 2012AA02A518). National Science Foundation of China (30890034). National Basic Research Program (2012CB944600). Scientific and Technological Support Plans from Jiangsu Province (BE2010715). NLCS (H.S.)—China National High-Tech Research and Development Program Grant (2009AA022705). Priority Academic Program Development of Jiangsu Higher Education Institution. National Key Basic Research Program Grant (2011CB503805). GEL-S (A.S.)—National Medical Research Council Singapore grant (NMRC/0897/2004, NMRC/1075/2006). (J.Liu)—Agency for Science, Technology and Research (A*STAR) of Singapore. GELAC (C.A.H.)—National Research Program on Genomic Medicine in Taiwan (DOH98-TDG-111-015). National Research Program for Biopharmaceuticals in Taiwan (DOH 100TD-PB-111-TM013). National Science Council, Taiwan (NSC 1002319-B-400-001). YLCS (Q.L.)—Supported by the intramural program of U.S. National Institutes of Health, National Cancer Institute. SWHS (W.Z., W-H.C., N.R.)—The work was supported by a grant from the National Institutes of Health (R37 CA70867) and the National Cancer Institute intramural research program, including NCI Intramural Research Program contract (N02 CP1101066). JLCS (K.M., T.K.)—Grants-in-Aid from the Ministry of Health, Labor, and Welfare for Research on Applying Health Technology and for the 3rd-term Comprehensive 10-year Strategy for Cancer Control; by the National Cancer Center Research and Development Fund; by Grant-in-Aid for Scientific Research on Priority Areas and on Innovative Area from the Ministry of Education, Science, Sports, Culture and — Technology of Japan. (W.P.)—NCI R01-CA121210. HKS (J.W.)— General Research Fund of Research Grant Council, Hong Kong (781511M). The Environment and Genetics in Lung Cancer Etiology ( EAGLE ), Prostate, Lung, Colon, Ovary Screening Trial ( PLCO ), and Alpha-Tocopherol, Beta-Carotene Cancer Prevention ( ATBC ) studies were supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics. ATBC was also supported by U.S. Public Health Service contracts (N01-CN-45165, N01-RC-45035, and N01-RC-37004) from the NCI. PLCO was also supported by individual contracts from the NCI to the University of Colorado Denver (NO1-CN-25514), Georgetown University (NO1-CN-25522), the Pacific Health Research Institute (NO1-CN-25515), the Henry Ford Health System (NO1-CN-25512), the University of Minnesota, (NO1-CN25513), Washington University (NO1-CN-25516), the University of Pittsburgh (NO1-CN-25511), the University of Utah (NO1-CN25524), the Marshfield Clinic Research Foundation (NO1-CN25518), the University of Alabama at Birmingham (NO1-CN75022), Westat, Inc. (NO1-CN-25476), and the University of California, Los Angeles (NO1-CN-25404). The Cancer Prevention Study-II (CPS-II) Nutrition Cohort was supported by the American Cancer Society. The NIH Genes, Environment and Health Initiative ( GEI ) partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01 and RO1HL091172-01), genotyping at the Johns Hopkins University Center for Inherited Disease Research. Research and software development for gene-environment interaction analysis by Dr. Chatterjee was supported by funding from PCORI (ME-1602-34530) and NHGRI [1 R01 HG010480-01]. Work by Batel Blechter was supported by funding from the NCI ( T32 CA009314 ). Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2021",

month = feb,

doi = "10.1016/j.envint.2020.105975",

language = "English (US)",

volume = "147",

journal = "Environmental International",

issn = "0160-4120",

publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia

AU - Blechter, Batel

AU - Wong, Jason Y.Y.

AU - Agnes Hsiung, Chao

AU - Hosgood, H. Dean

AU - Yin, Zhihua

AU - Shu, Xiao Ou

AU - Zhang, Han

AU - Shi, Jianxin

AU - Song, Lei

AU - Song, Minsun

AU - Zheng, Wei

AU - Wang, Zhaoming

AU - Caporaso, Neil

AU - Burdette, Laurie

AU - Yeager, Meredith

AU - Berndt, Sonja I.

AU - Teresa Landi, Maria

AU - Chen, Chien Jen

AU - Chang, Gee Chen

AU - Hsiao, Chin Fu

AU - Tsai, Ying Huang

AU - Chen, Kuan Yu

AU - Huang, Ming Shyan

AU - Su, Wu Chou

AU - Chen, Yuh Min

AU - Chien, Li Hsin

AU - Chen, Chung Hsing

AU - Yang, Tsung Ying

AU - Wang, Chih Liang

AU - Hung, Jen Yu

AU - Lin, Chien Chung

AU - Perng, Reury Perng

AU - Chen, Chih Yi

AU - Chen, Kun Chieh

AU - Li, Yao Jen

AU - Yu, Chong Jen

AU - Chen, Yi Song

AU - Chen, Ying Hsiang

AU - Tsai, Fang Yu

AU - Jie Seow, Wei

AU - Bassig, Bryan A.

AU - Hu, Wei

AU - Ji, Bu Tian

AU - Wu, Wei

AU - Guan, Peng

AU - He, Qincheng

AU - Gao, Yu Tang

AU - Cai, Qiuyin

AU - Chow, Wong Ho

AU - Xiang, Yong Bing

AU - Lin, Dongxin

AU - Wu, Chen

AU - Wu, Yi Long

AU - Shin, Min Ho

AU - Hong, Yun Chul

AU - Matsuo, Keitaro

AU - Chen, Kexin

AU - Pik Wong, Maria

AU - Lu, Daru

AU - Jin, Li

AU - Wang, Jiu Cun

AU - Seow, Adeline

AU - Wu, Tangchun

AU - Shen, Hongbing

AU - Fraumeni, Joseph F.

AU - Yang, Pan Chyr

AU - Chang, I. Shou

AU - Zhou, Baosen

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Chatterjee, Nilanjan

AU - Lan, Qing

N1 - Funding Information: The FLCCA was supported in part by intramural funding from National Cancer Institute . Further funding was provided by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan , a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry Health, Labor and Welfare of Japan , by Health and Labor Sciences Research Grants for Research on Applying Health Technology from the Ministry of Health, Labor and Welfare of Japan , by the National Cancer Center Research and Development Fund, the National Research Foundation of Korea ( NRF ) grant funded by the Korea government ( MEST ) (grant No. 2011-0016106 ), a grant of the National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea ( A111218-11-GM04 ), the Program for Changjiang Scholars and Innovative Research Team in University in China (IRT_14R40 to K.C.), the National Science & Technology Pillar Program (2011BAI09B00), MOE 111 Project (B13016), the National Natural Science Foundation of China (No. 30772531 , and 81272618 ), Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine (No. 2012A061400006 ), Special Fund for Research in the Public Interest from the National Health and Family Planning Commission of PRC (No. 201402031 ), and the Ministry of Science and Technology, Taiwan ( MOST 103-2325-B-400-023 & 104-2325-B-400-012 ). The Japan Lung Cancer Study ( JLCS ) was supported in part by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development ( 15ck0106096h0002 ) and the Management Expenses Grants from the Government to the National Cancer Center (26-A-1) for Biobank. BioBank Japan was supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government. The Japan Public Health Center-based prospective Study (the JPHC Study) was supported by the National Cancer Center Research and Development Fund (23-A31[toku] and 26-A-2) (since 2011) and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010). The Taiwan GELAC Study (Genetic Epidemiological Study for Lung AdenoCarcinoma) was supported by grants from the National Research Program on Genomic Medicine in Taiwan (DOH99-TD-G-111-028), the National Research Program for Biopharmaceuticals in Taiwan (MOHW 103-TDUPB-211-144003, MOST 103-2325-B-400-023) and the Bioinformatics Core Facility for Translational Medicine and Biotechnology Development (MOST 104-2319-B-400-002). This work was also supported by the Jinan Science Research Project Foundation (201102051), the National Key Scientific and Technological Project (2011ZX09307-001-04), the National Natural Science Foundation of China (No.81272293), the State Key Program of National Natural Science of China (81230067), the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. NRF2014R1A2A2A05003665), Sookmyung Women’s University Research Grants, Korea (1-1603-2048), Agency for Science, Technology and Research (A*STAR), Singapore and the US National Institute of Health Grant (1U19CA148127-01). The overall GWAS project was supported by the intramural program of the US National Institutes of Health/National Cancer Institute. The following is a list of grants by study center: SKLCS (Y.T.K.)—National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2011-0016106). (J.C.) – This work was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health &Welfare, Republic of Korea (grant no. 0720550-2). (J.S.S) – grant number is A010250. WLCS (T.W.)—National Key Basic Research and Development Program (2011CB503800). SLCS (B.Z.)—National Nature Science Foundation of China (81102194). Liaoning Provincial Department of Education (LS2010168). China Medical Board (00726). GDS (Y.L.W.)—Foundation of Guangdong Science and Technology Department (2006B60101010, 2007A032000002, 2011A030400010). Guangzhou Science and Information Technology Bureau (2011Y2-00014). Chinese Lung Cancer Research Foundation, National Natural Science Foundation of China (81101549). Natural Science Foundation of Guangdong Province (S2011010000792). TLCS (K.C., B.Q)—Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT), China (IRT1076). Tianjin Cancer Institute and Hospital. National Foundation for Cancer Research (US). FLCS (J.C.W., D.R., L.J.)—Ministry of Health (201002007). Ministry of Science and Technology (2011BAI09B00). National S&T Major Special Project (2011ZX09102-010-01). China National High-Tech Research and Development Program (2012AA02A517, 2012AA02A518). National Science Foundation of China (30890034). National Basic Research Program (2012CB944600). Scientific and Technological Support Plans from Jiangsu Province (BE2010715). NLCS (H.S.)—China National High-Tech Research and Development Program Grant (2009AA022705). Priority Academic Program Development of Jiangsu Higher Education Institution. National Key Basic Research Program Grant (2011CB503805). GEL-S (A.S.)—National Medical Research Council Singapore grant (NMRC/0897/2004, NMRC/1075/2006). (J.Liu)—Agency for Science, Technology and Research (A*STAR) of Singapore. GELAC (C.A.H.)—National Research Program on Genomic Medicine in Taiwan (DOH98-TDG-111-015). National Research Program for Biopharmaceuticals in Taiwan (DOH 100TD-PB-111-TM013). National Science Council, Taiwan (NSC 1002319-B-400-001). YLCS (Q.L.)—Supported by the intramural program of U.S. National Institutes of Health, National Cancer Institute. SWHS (W.Z., W-H.C., N.R.)—The work was supported by a grant from the National Institutes of Health (R37 CA70867) and the National Cancer Institute intramural research program, including NCI Intramural Research Program contract (N02 CP1101066). JLCS (K.M., T.K.)—Grants-in-Aid from the Ministry of Health, Labor, and Welfare for Research on Applying Health Technology and for the 3rd-term Comprehensive 10-year Strategy for Cancer Control; by the National Cancer Center Research and Development Fund; by Grant-in-Aid for Scientific Research on Priority Areas and on Innovative Area from the Ministry of Education, Science, Sports, Culture and — Technology of Japan. (W.P.)—NCI R01-CA121210. HKS (J.W.)— General Research Fund of Research Grant Council, Hong Kong (781511M). The Environment and Genetics in Lung Cancer Etiology ( EAGLE ), Prostate, Lung, Colon, Ovary Screening Trial ( PLCO ), and Alpha-Tocopherol, Beta-Carotene Cancer Prevention ( ATBC ) studies were supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics. ATBC was also supported by U.S. Public Health Service contracts (N01-CN-45165, N01-RC-45035, and N01-RC-37004) from the NCI. PLCO was also supported by individual contracts from the NCI to the University of Colorado Denver (NO1-CN-25514), Georgetown University (NO1-CN-25522), the Pacific Health Research Institute (NO1-CN-25515), the Henry Ford Health System (NO1-CN-25512), the University of Minnesota, (NO1-CN25513), Washington University (NO1-CN-25516), the University of Pittsburgh (NO1-CN-25511), the University of Utah (NO1-CN25524), the Marshfield Clinic Research Foundation (NO1-CN25518), the University of Alabama at Birmingham (NO1-CN75022), Westat, Inc. (NO1-CN-25476), and the University of California, Los Angeles (NO1-CN-25404). The Cancer Prevention Study-II (CPS-II) Nutrition Cohort was supported by the American Cancer Society. The NIH Genes, Environment and Health Initiative ( GEI ) partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01 and RO1HL091172-01), genotyping at the Johns Hopkins University Center for Inherited Disease Research. Research and software development for gene-environment interaction analysis by Dr. Chatterjee was supported by funding from PCORI (ME-1602-34530) and NHGRI [1 R01 HG010480-01]. Work by Batel Blechter was supported by funding from the NCI ( T32 CA009314 ). Publisher Copyright: © 2020 The Authors

PY - 2021/2

Y1 - 2021/2

N2 - We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10−26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10−3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

AB - We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10−26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10−3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

KW - Gene-environment interaction

KW - Household coal use

KW - Lung adenocarcinoma

KW - Never-smoking women in Asia

KW - Polygenic risk score

UR - http://www.scopus.com/inward/record.url?scp=85098869659&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85098869659&partnerID=8YFLogxK

U2 - 10.1016/j.envint.2020.105975

DO - 10.1016/j.envint.2020.105975

M3 - Article

C2 - 33385923

AN - SCOPUS:85098869659

SN - 0160-4120

VL - 147

JO - Environmental International

JF - Environmental International

M1 - 105975

ER -

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia

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