Wang, Xiaoyu
https://orcid.org/0009-0005-5143-6909
Mayo Clinic
Frederick National Laboratory for Cancer Research
Citations 1
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.