Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report.
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN
1556-1380
Date Issued
2025
Author(s)
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
Wong, Jason Y Y
Dai, Juncheng
Hosgood, H Dean
Wang, Zhaoming
Chang, I-Shou
Choi, Jiyeon
Wang, Jiucun
Song, Minsun
Hu, Wei
Zheng, Wei
Kim, Jin Hee
Zhou, Baosen
Albanes, Demetrius
Shin, Min-Ho
Chung, Lap Ping
An, She-Juan
Zheng, Hong
Yatabe, Yasushi
Zhang, Xu-Chao
Kim, Young Tae
Shu, Xiao-Ou
Kim, Young-Chul
Vermeulen, Roel C H
Bassig, Bryan A
Chang, Jiang
Man Ho, James Chung
Ji, Bu-Tian
Kubo, Michiaki
Daigo, Yataro
Momozawa, Yukihide
Kamatani, Yoichiro
Honda, Takayuki
Kunitoh, Hideo
Watanabe, Shun-Ichi
Miyagi, Yohei
Nakayama, Haruhiko
Matsumoto, Shingo
Tsuboi, Masahiro
Goto, Koichi
Yin, Zhihua
Takahashi, Atsushi
Goto, Akiteru
Minamiya, Yoshihiro
Shimizu, Kimihiro
Tanaka, Kazumi
Wu, Tangchun
Wei, Fusheng
Su, Jian
Kim, Yeul Hong
Oh, In-Jae
Fun Lee, Victor Ho
Su, Wu-Chou
Chen, Yuh-Min
Chang, Gee-Chen
Huang, Ming-Shyan
Lin, Hsien-Chih
Seow, Adeline
Park, Jae Yong
Kweon, Sun-Seog
Chen, Chien-Jen
Gao, Yu-Tang
Wu, Chen
Qian, Biyun
Lu, Daru
Liu, Jianjun
Jeon, Hyo-Sung
Hsiao, Chin-Fu
Sung, Jae Sook
Tsai, Ying-Huang
Jung, Yoo Jin
Guo, Huan
Hu, Zhibin
Chen, Tzu-Yu
Burdett, Laurie
Yeager, Meredith
Hutchinson, Amy
Berndt, Sonja I
Wu, Wei
Wang, Junwen
Choi, Jin Eun
Park, Kyong Hwa
Sung, Sook Whan
Liu, Li
Kang, Chang Hyun
Chen, Chung-Hsing
Xu, Jun
Guan, Peng
Tan, Wen
Wang, Chih-Liang
Loon Sihoe, Alan Dart
Chen, Ying
Choi, Yi Young
Kim, Jun Suk
Yoon, Ho-Il
Cai, Qiuyin
Park, In Kyu
Xu, Ping
He, Qincheng
Chen, Chih-Yi
Wu, Junjie
Lim, Wei-Yen
Chen, Kun-Chieh
Chan, John K C
Li, Jihua
Chen, Hongyan
Jin, Li
Fraumeni, Joseph F
Liu, Jie
Landi, Maria Teresa
Yamaji, Taiki
Yang, Yang
Hicks, Belynda
Wyatt, Kathleen
Li, Shengchao A
Ma, Hongxia
Song, Bao
Wang, Zhehai
Cheng, Sensen
Li, Xuelian
Ren, Yangwu
Iwasaki, Motoki
Zhu, Junjie
Jiang, Gening
Fei, Ke
Wu, Guoping
Chien, Li-Hsin
Tsai, Fang-Yu
Yu, Jinming
Stevens, Victoria L
Lin, Dongxin
Chen, Kexin
Wu, Yi-Long
Matsuo, Keitaro
Rothman, Nathaniel
Shiraishi, Kouya
Shen, Hongbing
Chanock, Stephen J
Kohno, Takashi
Lan, Qing
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). 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.
Subjects
EGFR mutation
Lung adenocarcinoma
Never-smokers
Polygenic risk score
SDGs
Type
journal article