Citations 3
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.
Abstract 4626: Genetic susceptibility to diffuse large B-cell lymphoma in a pooled study of three Eastern Asian populations
Rothman, Nathaniel , Bassig, Bryan A. , Au, Wing‐Yan, Sangrajrang, Suleeporn , Tse, Jovic, Berndt, Sonja I. , Zheng, Tongzhang, Zhang, Heping , Pornsopone, Pattarapong, Lee, Je‐Jung , Kim, Hyeoung‐Joon , Skibola, Christine F., Burdette, Laurie , Brennan, Paul , Liang, Raymond , Chanock, Stephen, Lan, Qing , Rothman, Nathaniel , Cerhan, James R. , Kim, Hee Nam , Hu, Wei, Vijai, Joseph , Yeager, Meredith , Shin, Min‐Ho
Cancer Research | August 5, 2015 | Volume: 75 | Issue: 15_Supplement | Pages: 4626-4626
Abstract Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL) and is the most common NHL subtype diagnosed worldwide. Some epidemiologic data have indicated differences in DLBCL incidence rates and subtype distributions between Eastern Asian and Western countries. The first large-scale genome-wide association study (GWAS) of DLBCL with over 4000 cases conducted among individuals of European ancestry recently identified five independent SNPs that achieved genome-wide significance, and two SNPs that showed a suggestive association with DLBCL risk. In order to evaluate whether Eastern Asians and individuals of European ancestry share similar genetic risk factors for this disease, we attempted to replicate these GWAS findings in a pooled series of 1124 DLBCL cases and 3596 controls from Hong Kong, South Korea, and Thailand. Three of the five genome-wide significant SNPs from the DLBCL GWAS were significantly associated with DLBCL in our study population, including the top finding from the GWAS, EXOC2 rs116446171, which achieved genome-wide significance in our data (per allele OR = 2.04, 95% CI = 1.63-2.56; ptrend = 3.9 × 10-10). Additionally, we observed a significant association with PVT1 rs13255292 (per allele OR = 1.34, 95% CI = 1.19-1.52; ptrend = 2.1 × 10-6), which was the second strongest finding in the GWAS, and with HLA-B rs2523607 (per allele OR = 3.05, 95% CI = 1.32-7.05; ptrend = 0.009). Our study, which provides the first evaluation in Eastern Asians of SNPs definitively associated with DLBCL risk in individuals of European ancestry, indicates that at least some of the genetic factors associated with risk of DLBCL are similar between these populations. Citation Format: Nathaniel Rothman, Bryan A. Bassig, James R. Cerhan, Wing-Yan Au, Hee Nam Kim, Suleeporn Sangrajrang, Wei Hu, Jovic Tse, Sonja Berndt, Tongzhang Zheng, Heping Zhang, Pattarapong Pornsopone, Je-Jung Lee, Hyeoung-Joon Kim, Christine F. Skibola, Joseph Vijai, Laurie Burdette, Meredith Yeager, Paul Brennan, Min-Ho Shin, Raymond Liang, Stephen Chanock, Qing Lan. Genetic susceptibility to diffuse large B-cell lymphoma in a pooled study of three Eastern Asian populations. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4626. doi:10.1158/1538-7445.AM2015-4626
Genetic susceptibility to diffuse large B‐cell lymphoma in a pooled study of three Eastern Asian populations
Bassig, Bryan A. , Au, Wing‐Yan, Sangrajrang, Suleeporn , Tse, Jovic, Berndt, Sonja I. , Zheng, Tongzhang, Pornsopone, Pattarapong, Lee, Je‐Jung , Kim, Hyeoung‐Joon , Skibola, Christine F., Vijai, Joseph , Burdette, Laurie , Brennan, Paul , Liang, Raymond , Lan, Qing , Rothman, Nathaniel , Cerhan, James R. , Kim, Hee Nam , Hu, Wei , Zhang, Heping , Yeager, Meredith , Shin, Min‐Ho , Chanock, Stephen Jacob , Rothman, Nathaniel , Joseph, Vijai
European Journal of Haematology | January 22, 2015 | Volume: 95 | Issue: 5 | Pages: 442-448
AbstractObjectivesDiffuse large B‐cell lymphoma (DLBCL) is an aggressive subtype of non‐Hodgkin lymphoma (NHL) and is the most common NHL subtype diagnosed worldwide. The first large‐scale genome‐wide association study (GWAS) of DLBCL with over 4000 cases conducted among individuals of European ancestry recently identified five independent SNPs that achieved genome‐wide significance, and two SNPs that showed a suggestive association with DLBCL risk.MethodsTo evaluate whether Eastern Asians and individuals of European ancestry share similar genetic risk factors for this disease, we attempted to replicate these GWAS findings in a pooled series of 1124 DLBCL cases and 3596 controls from Hong Kong, South Korea, and Thailand.ResultsThree of the five genome‐wide significant SNPs from the DLBCL GWAS were significantly associated with DLBCL in our study population, including the top finding from the GWAS, EXOC2 rs116446171, which achieved genome‐wide significance in our data (per allele OR = 2.04, 95% CI = 1.63–2.56; ptrend = 3.9 × 10−10). Additionally, we observed a significant association with PVT1 rs13255292 (per allele OR = 1.34, 95% CI = 1.19–1.52; ptrend = 2.1 × 10−6), which was the second strongest finding in the GWAS, and with HLA‐B rs2523607 (per allele OR = 3.05, 95% CI = 1.32–7.05; ptrend = 0.009).ConclusionsOur study, which provides the first evaluation in Eastern Asians of SNPs definitively associated with DLBCL risk in individuals of European ancestry, indicates that at least some of the genetic factors associated with risk of DLBCL are similar between these populations.