Citations 2
Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers
Blechter, Batel , Wang, Xiaoyu , Karsonaki, Christiana, Shi, Jianxin , Shiraishi, Kouya , Choi, Jiyeon , Matsuo, Keitaro , Chen, Tzu‐Yu , Kim, Young Tae , Choudhury, Parichoy Pal , Williams, Jacob , Landi, Maria Teresa , Yin, Zhihua , Zhou, Baosen , Seow, Wei Jie , Song, Lei , Chang, I‐Shou , Chien, Li-Hsin , Wong, Maria Pik , Richardson, Brian Douglas , Li, Shilan , Breeze, Charles E. , Bassig, Bryan A. , Sm, Jason Yy Wong, Chung, Lap Ping, Zhang, Xu‐Chao , Caporaso, Neil E. , Chang, Jiang , Ho, Jcm , Momozawa, Yukihide , Kobayashi, Masashi , Okubo, Kenichi , Honda, Takayuki , Kunitoh, Hideo , Watanabe, Shun-ichi, Hamamoto, Ryuji , Goto, Kōichi , Minamiya, Yoshihiro, Wakai, Kenji , Murakami, Yoshinori , Shimizu, Kimihiro , Suzuki, Hiroyuki , Ohtaki, Yoichi , Tanaka, Kazumi , Wu, Tangchun , Wei, Fusheng, Kim, Yeul Hong , Chang, Gee-Chen , Chen, Kuan‐Yu, Chen, Yuh-Min, Park, Jae Yong , Kweon, Sun-Seog, Gao, Yu‐Tang , Schwartz, Ann G. , Gorlov, Ivan , Wu, Xifeng , Yang, Ping , Lam, Stephen , Bojesen, Stig E. , Ji, Bu‐Tian , Wichmann, H. E., Christiani, D.C., Brennan, Paul , McKay, James , Field, John K. , Shete, Sanjay , Marchand, Loı̈c Le, Liu, Geoffrey , Andrew, Angeline S. , Zienolddiny-Narui, Shan, Grankvist, Kjell , Taylor, Fiona, Aldrich, Melinda C. , Jeon, Hyo‐Sung, Hu, Zhibin , Burdett, Laura, Yeager, Meredith, Hutchinson, Amy , Hicks, Belynda , Liu, Jia , Berndt, Sonja I, Wu, Wei , Wang, Junwen , Choi, Jin Eun , Park, Kyong Hwa , Sung, Sook Whan , Tan, Wen , Sihoe, Alan , Choi, Yi Young, Hung, Hsiao-Han , Vermeulen, Roel , Wu, Junjie , Tsai, Fang-Yu , Chan, John K. C., Li, Jihua , Lin, Hsien-Chih, Liu, Jie , Sawada, Norie , Yamaji, Taiki , Wyatt, Kathleen , Qi, T. Y., Li, Xuelian , Ren, Yangwu , Chao, Ann, Zhu, Junjie , Chen, Chih‐Yi , ScD, Chien-Jen Chen, Stevens, Victoria L. , Fraumeni, Joseph F., Lin, Kuang , Walters, Robin G., Chen, Zhengming, Chatterjee, Nilanjan , Gorlova, Olga Y. , Hsiung, Chao A. , Chanock, Stephen J, Rothman, Nathaniel , Kohno, Takashi , Lan, Qing, Kartsonaki, Christiana , Liu, Geoffrey , Field, John K , Matsuo, Keitaro , Wang, Junwen , Bojesen, Stig E , Grankvist, Kjell , Chen, Chih-Yi , Dai, Juncheng , Hung, Rayjean J. , Chen, Kexin , Shu, Xiao-Ou , Choudhury, Parichoy Pal , Lin, Dongxin , Zheng, Wei , Wang, Jiucun , Hu, Wei , Cai, Qiuyin , Hong, Yun‐Chul , Kim, Hee Nam , Wu, Yi-Long Lung Cancer , Richardson, Brian Douglas , Zhang, Tongwu , Wang, Zhaoming , Kim, Jin Hee , Albanes, Demetrius , Shin, Min‐Ho , Chung, Lap-Ping, Yang, Yang , Zheng, Hong , Dai, Hong , Yatabe, Yasushi , Kim, Young‐Chul , Daigo, Yataro , Kamatani, Yoichiro , Kobayashi, Masashi , Hosgood, Howard Dean , WATANABE, Shun-ichi J. , Miyagi, Yohei , Matsumoto, Shingo , Horinouchi, Hidehito , Tsuboi, Masahiro , Takahashi, Atsushi , Goto, Akiteru , Hara, Megumi , Nishida, Yuichiro , Takeuchi, Kenji , Matsuda, Koichi , Murakami, Yoshinori, Suzuki, Hiroyuki , Saito, Motonobu , Machiela, Mitchell J. , Oh, In‐Jae , Lee, Victor , Su, Wu‐Chou , Seow, Adeline , Kweon, Sun-Seog , Liu, Jianjun , Houlston, Richard S. , Tardón, Adonina , Chen, Chu, Johansson, Mattias , Risch, Angela , Bickeböller, Heike , Rennert, Gad , Arnold, Susanne M. , Davies, Michael P.A. , Kiemeney, Lambertus A. , Cox, Angela , Yuan, Jian-Min , Lazarus, Philip J. , Schabath, Matthew B. , Jiang, Shih Sheng , Chen, Chung–Hsing , Hsiao, Chin‐Fu , Yeager, Meredith , Liu, Jia , Berndt, Sonja I. , Li, Yuqing , Kang, Chang Hyun , Wang, Wen‐Chang , Xu, Jun, Guan, Peng , Yu, Chong‐Jen , Yang, Gong , Park, In Kyu , Cheng, Iona C. , Song, Bao, Wyatt, Kathleen , Ma, Hongxia , Zhu, Meng , Wang, Yifan , Qi, Tianchen, Iwasaki, Motoki , Wu, Guoping , Yang, Pan‐Chyr , Walters, Robin G. , Chatterjee, Nilanjan , Amos, Christopher I. , Shen, Hongbing , Rothman, Nathaniel , Lan, Qing , Zhang, Haoyu
JNCI: Journal of the National Cancer Institute | September 18, 2025 | Volume: 118 | Issue: 2 | Pages: 231-249
Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.
Genome-Wide Association Study of Genetic Predictors of Overall Survival for Non–Small Cell Lung Cancer in Never Smokers
Wu, Xifeng , Ye, Yuanqing , Aakre, Jeremiah A. , Chang, Gee-Chen , Yang, Pan‐Chyr , Roth, Jack A. , Marks, Randolph S., Lippman, Scott M. , Deschamps, Claude, Su, Wu‐Chou , Wang, Wen‐Chang , Huang, Ming‐Shyan , Chang, David W. , Hong, Waun Ki , Hsiung, Chao A. , Wang, Liang , Pu, Xia , Chang, Joe Y. , Lu, Charles , Li, Yan , Pankratz, V. Shane , Minna, John Dorrance , Hildebrandt, Michelle A.T. , Yang, Ping
Cancer Research | May 24, 2013 | Volume: 73 | Issue: 13 | Pages: 4028-4038
Abstract To identify the genetic factors that influence overall survival in never smokers who have non–small cell lung carcinoma (NSCLC), we conducted a consistency meta-analysis study using genome-wide association approaches for overall survival in 327 never smoker patients with NSCLC from The University of Texas MD Anderson Cancer Center (Houston, TX) and 293 cases from the Mayo Clinic (Rochester, MN). We then conducted a two-pronged validation of the top 25 variants that included additional validation in 1,256 patients with NSCLC from Taiwan and assessment of expression quantitative trait loci (eQTL) and differential expression of genes surrounding the top loci in 70 tumors and matched normal tissues. A total of 94 loci were significant for overall survival in both MD Anderson and Mayo studies in the consistency meta-analysis phase, with the top 25 variants reaching a P value of 10−6. Two variants of these 25 were also significant in the Taiwanese population: rs6901416 [HR, 1.44; 95% confidence interval (CI), 1.01–2.06] and rs10766739 (HR, 1.23; 95%CI, 1.00–1.51). These loci resulted in a reduction of median survival time of at least eight and five months in three populations, respectively. An additional six variants (rs4237904, rs7976914, rs4970833, rs954785, rs485411, and rs10906104) were validated through eQTL analysis that identified significant correlations with expression levels of six genes (LEMD3, TMBIM, ATXN7L2, SHE, ITIH2, and NUDT5, respectively) in normal lung tissue. These genes were also significantly differentially expressed between the tumor and normal lung tissue. These findings identify several novel, candidate prognostic markers for NSCLC in never smokers, with eQTL analysis suggesting a potential biologic mechanism for a subset of these observed associations. Cancer Res; 73(13); 4028–38. ©2013 AACR.