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

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

10 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

General Environmental Science

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10.1016/j.envint.2020.105975

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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, Article 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

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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 = "Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2021",

month = feb,

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

language = "English (US)",

volume = "147",

journal = "Environment 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

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

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DO - 10.1016/j.envint.2020.105975

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AN - SCOPUS:85098869659

SN - 0160-4120

VL - 147

JO - Environment international

JF - Environment 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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