Liu, Jia
Mayo Clinic
Frederick National Laboratory for Cancer Research
Citations 2
Different diabetes types and pancreatic ductal adenocarcinoma: a Mendelian randomization and pathway/gene-set analysis
Zhang, Ting , Mohindroo, Chirayu , Wang, Xiaoyu , Dutta, Diptavo , Liu, Jia , Katta, Shilpa, Li, Shengchao A. , Wang, Jiahui , Antwi, Samuel O. , Bracci, Paige M. , Du, Mengmeng, Gallinger, Steven , Goodman, Phyllis J. , Katzke, Verena, Patel, Alpa V. , Visvanathan, Kala , Andreotti, Gabriella , Brennan, Paul , Buring, Julie E. , Chanock, Stephen J., Chen, Yu , Giovannucci, Edward L. , Haiman, Christopher A. , Hassan, Manal M. , Holly, Elizabeth A., Jones, Miranda R. , Kraft, Peter, Kurtz, Robert C. , Ng, Kimmie , Oberg, Ann L. , Peters, Ulrike , Rabe, Kari G. , Rothman, Nathaniel , Sesso, Howard D. , Yuan, Chen, Wolpin, Brian M. , Yu, Kai , Stolzenberg‐Solomon, Rachael Z. , Mohindroo, Chirayu , Wang, Xiaoyu , Dutta, Diptavo , Liu, Jia , Li, Shengchao A , Antwi, Samuel O , Arslan, Alan A , Beane Freeman, Laura E , Canzian, Federico , Du, Mengmeng , Goodman, Phyllis J , Katzke, Verena , Kooperberg, Charles , Marchand, Loïc Le , Neale, Rachel E , Perdomo, Sandra , Shu, Xiao-Ou , Visvanathan, Kala , Van Den Eeden, Stephen K , White, Emily E. , Zheng, Wei , Albanes, Demetrius , Andreotti, Gabriella , Brennan, Paul , Buring, Julie E , Chanock, Stephen Jacob , Chen, Yu , Darst, Burcu F , Ferrari, Pietro , Giovannucci, Edward L , Goggins, Michael G , Haiman, Christopher A , Hassan, Manal M , Hung, Rayjean J , Jones, Miranda R , Kraft, Peter , Malats, Nuria , Moore, Steven C , Ng, Kimmie , Oberg, Ann L , Orlow, Irene , Peters, Ulrike , Porta, Miquel , Chaffee, Kari G. , Sánchez, Maria-Jose , Sesso, Howard D , Southey, Melissa C , Um, Caroline Y , Yarmolinsky, James , Yu, Herbert , Yuan, Chen , Zhong, Jun , Wolpin, Brian M , Risch, Harvey A , Amundadottir, Laufey , Klein, Alison P , Yu, Kai , Zhang, Haoyu , Stolzenberg-Solomon, Rachael , Zhang, Ting , Hua, Xing , Arslan, Alan A. , Freeman, Laura E. Beane , Canzian, Federico , Kooperberg, Charles , Marchand, Loı̈c Le , Neale, Rachel Ε. , Zheng, Wei , Albanes, Demetrius , Bamlet, William R. , Darst, Burcu F. , Goggins, Michael , Hung, Rayjean J. , Malats, Núria , Moore, Steven C. , Orlow, Irene , Porta, Miquel , Sánchez, María‐José , Silverman, Debra T. , Southey, Melissa C. , Um, Caroline Y. , Yu, Kai , Risch, Harvey A. , Ámundadóttir, Laufey T. , Klein, Alison P.
JNCI: Journal of the National Cancer Institute | November 8, 2025 | Volume: 118 | Issue: 3 | Pages: 437-447
Abstract Background The associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood. Methods We investigated associations of genetic susceptibility to type 2 diabetes (T2D), 8 T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242 283 cases, 1 569 734 controls), T1D (18 942 cases, 501 638 controls), and PDAC (10 244 cases and 360 535 controls) in individuals of European ancestry. Results Two-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI = 1.05 to 1.15), particularly the T2D obesity (OR = 1.28; 95% CI = 1.15 to 1.42) and lipodystrophy (OR = 1.25; 95% CI = 1.03 to 1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI = 0.99 to 1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10−8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10−4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions. Conclusions Our results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.
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.