Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report
Publication date
2025-04
Authors
Blechter, Batel
Hsiung, Chao Agnes
Wang, Xiaoyu
Zhang, Haoyu
Seow, Wei Jie
Shi, Jianxin
Chatterjee, Nilanjan
Kim, Hee Nam
Wong, Maria Pik
Hong, Yun Chul
Editors
Advisors
Supervisors
Document Type
Article
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taverne
Abstract
We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the EGFR gene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared with EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (odds ratio = 8.63, 95% confidence interval: 5.67–13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (odds ratio = 3.50, 95% confidence interval: 2.44–5.00) (p-heterogeneity = 3.66 × 10−3). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications.
Keywords
EGFR mutation, Lung adenocarcinoma, Never-smokers, Polygenic risk score, Taverne, Oncology, Pulmonary and Respiratory Medicine, SDG 3 - Good Health and Well-being
Citation
Blechter, B, Hsiung, C A, Wang, X, Zhang, H, Seow, W J, Shi, J, Chatterjee, N, Kim, H N, Wong, M P, Hong, Y C, Wong, J Y Y, Dai, J, Hosgood, H D, Wang, Z, Chang, I S, Choi, J, Wang, J, Song, M, Hu, W, Zheng, W, Kim, J H, Zhou, B, Albanes, D, Shin, M H, Chung, L P, An, S J, Zheng, H, Yatabe, Y, Zhang, X C, Kim, Y T, Shu, X O, Kim, Y C, Vermeulen, R C H, Bassig, B A, Chang, J, Man Ho, J C, Ji, B T, Kubo, M, Daigo, Y, Momozawa, Y, Kamatani, Y, Honda, T, Kunitoh, H, Watanabe, S I, Miyagi, Y, Nakayama, H, Matsumoto, S, Tsuboi, M, Goto, K, Yin, Z, Takahashi, A, Goto, A, Minamiya, Y, Shimizu, K, Tanaka, K, Wu, T, Wei, F, Su, J, Kim, Y H, Oh, I J, Fun Lee, V H, Su, W C, Chen, Y M, Chang, G C, Chen, K Y, Huang, M S, Lin, H C, Seow, A, Park, J Y, Kweon, S S, Chen, C J, Gao, Y T, Wu, C, Qian, B, Lu, D, Liu, J, Jeon, H S, Hsiao, C F, Sung, J S, Tsai, Y H, Jung, Y J, Guo, H, Hu, Z, Chen, T Y, Burdett, L, Yeager, M, Hutchinson, A, Berndt, S I, Wu, W, Wang, J, Choi, J E, Park, K H, Sung, S W, Liu, L, Kang, C H, Chen, C H, Xu, J, Guan, P, Tan, W, Wang, C L, Loon Sihoe, A D, Chen, Y, Choi, Y Y, Kim, J S, Yoon, H I, Cai, Q, Park, I K, Xu, P, He, Q, Chen, C Y, Wu, J, Lim, W Y, Chen, K C, Chan, J K C, Li, J, Chen, H, Yu, C J, Jin, L, Fraumeni, J F, Liu, J, Landi, M T, Yamaji, T, Yang, Y, Hicks, B, Wyatt, K, Li, S A, Ma, H, Song, B, Wang, Z, Cheng, S, Li, X, Ren, Y, Iwasaki, M, Zhu, J, Jiang, G, Fei, K, Wu, G, Chien, L H, Tsai, F Y, Yu, J, Stevens, V L, Yang, P C, Lin, D, Chen, K, Wu, Y L, Matsuo, K, Rothman, N, Shiraishi, K, Shen, H, Chanock, S J, Kohno, T & Lan, Q 2025, 'Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status : A Brief Report', Journal of Thoracic Oncology, vol. 20, no. 4, pp. 521-530. https://doi.org/10.1016/j.jtho.2024.11.019