基于表皮生长因子受体（EGFR）突变状态的多基因风险评分与从不吸烟者的肺腺癌风险：简要报告

Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report.

作者信息

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, Chen Kuan-Yu, 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, Yu Chong-Jen, 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, Yang Pan-Chyr, Lin Dongxin, Chen Kexin, Wu Yi-Long, Matsuo Keitaro, Rothman Nathaniel, Shiraishi Kouya, Shen Hongbing, Chanock Stephen J, Kohno Takashi, Lan Qing

机构信息

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.

出版信息

J Thorac Oncol. 2025 Apr;20(4):521-530. doi: 10.1016/j.jtho.2024.11.019. Epub 2024 Nov 22.

DOI:10.1016/j.jtho.2024.11.019

PMID:39581378

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.

摘要

我们使用病例对照和多项回归分析，评估了针对肺腺癌（LUAD）风险开发的全基因组多基因风险评分（PRS）与998例东亚从不吸烟女性LUAD病例（518例EGFR阳性；480例EGFR阴性）和4544例从不吸烟对照中EGFR基因的突变之间的关联。我们发现，与EGFR阴性LUAD相比，PRS与EGFR阳性LUAD的关联更强，其中PRS第四四分位数与EGFR阳性LUAD之间的关联（优势比=8.63，95%置信区间：5.67-13.14）显著高于PRS第四四分位数与EGFR阴性LUAD之间的关联（优势比=3.50，95%置信区间：2.44-5.00）（p异质性=3.66×10）。我们的研究结果表明，在东亚从不吸烟的女性患者中，生殖系遗传易感性可能根据癌症的突变状态与LUAD存在差异关联，这可能具有重要的公共卫生和临床意义。