Citations 3
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.
Genetically determined body mass index is associated with diffuse large B‐cell lymphoma in polygenic and Mendelian randomization analyses
Moore, Amy , Teras, Lauren R. , Machiela, Mitchell J. , Arias, Joshua , Monnereau, Alain , Wang, Zhaoming , Vermeulen, Roel , Smedby, Karin E. , Spinelli, John J., Nieters, Alexandra , Bracci, Paige M. , Camp, Nicola J. , Hjalgrim, Henrik, Adami, Hans‐Olov , Albanes, Demetrius, Becker, Nikolaus, Benavente, Yolanda , Clavel, Jacqueline , Curtin, Karen , Ghesquières, Hervé, Glimelius, Bengt, Lan, Qing , Liebow, Mark , McKay, James , Offit, Kenneth, Padoan, Marina, Patel, Alpa V. , Ríboli, Elio , Severson, Richard K., Tinker, Lesley F. , Weinstein, Stephanie J. , Zheng, Tongzhang, Chanock, Stephen J., Rothman, Nathaniel , Berndt, Sonja I. , Teras, Lauren R , Wang, Zhaoming , Vajdic, Claire M , De Vivo, Immaculata , Boffetta, Paolo , Brooks-Wilson, Angela R , Canzian, Federico , Southey, Melissa C , Cerhan, James R , Berndt, Sonja I , Clavel, Jacqueline , Machiela, Mitchell J , Riboli, Elio , Kane, Eleanor , Panagiotou, Orestis A. , Doo, Nicole Wong , Slager, Susan L. , Vajdic, Claire M. , Vijai, Joseph , Giles, Graham G. , Link, Brian K. , Arslan, Alan A. , Salles, Gilles , Cozen, Wendy , Vivo, Immaculata De , Albanes, Demetrius , Bisanzi, Simonetta , Brennan, Paul E. , Brooks‐Wilson, Angela , Canzian, Federico , Conde, Lucía , Cox, David G. , Foretová, Lenka , Glimelius, Bengt , Habermann, Thomas M. , Hofmann, Jonathan N. , Lan, Qing , Lincoln, Anne , Maynadié, Marc , Melbye, Mads , Miligi, Lucia , Milne, Roger L. , Molina, Thierry Jo , Morton, Lindsay M. , North, Kari E. , Offit, Kenneth, Piro, Sara , Purdue, Mark P. , Ravichandran, Vignesh , Southey, Melissa C. , Staines, Anthony , Travis, Ruth C. , Wang, Sophia , Weiderpass, Elisabete , Rothman, Nathaniel , Birmann, Brenda M. , Cerhan, James R.
International Journal of Cancer | September 5, 2025 | Volume: 158 | Issue: 1 | Pages: 45-59
Abstract Obesity has been associated with non‐Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome‐wide association studies of European ancestry ( N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist‐to‐hip ratio (WHR), and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05–1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR per SD = 1.12, 95% CI: 1.02–1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.
Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis
Kleinstern, Geffen , Camp, Nicola J. , Goldin, Lynn R. , Vachon, Celine M. , Vajdic, Claire M. , Sanjosé, Sílvia de, Weinberg, J. Brice , Benavente, Yolanda , Casabonne, Delphine, Liebow, Mark , Nieters, Alexandra, Hjalgrim, Henrik , Melbye, Mads , Glimelius, Bengt , Adami, Hans‐Olov , Brennan, Paul , McKay, James , Cocco, Pier Luigi, Call, Timothy G. , Hanson, Curtis A. , Robinson, Dennis P. , Chaffee, Kari G. , Brooks‐Wilson, Angela , Monnereau, Alain, Clavel, Jacqueline , Glenn, Martha, Curtin, Karen , Conde, Lucía , Bracci, Paige M. , Morton, Lindsay M. , Severson, Richard K., Chanock, Stephen J., Spinelli, John J., Johnston, James B. , Rothman, Nathaniel , Skibola, Christine F., Leis, José F., Smedby, Karin E. , Berndt, Sonja I. , Caporaso, Neil E., Rabe, Kari G. , Cocco, Pierluigi , Monnereau, Alain , Norman, Aaron D. , Hanson, Curtis, Robinson, Dennis, Cocco, Pierluigi , Brooks-Wilson, Angela R , Vajdic, Claire M , Morton, Lindsay M , Clavel, Jacqueline , Vachon, Celine M. , Casabonne, Delphine , Boffetta, Paolo , Maynadié, Marc , Shanafelt, Tait D. , Cozen, Wendy , Rothman, Nathaniel , Kay, Neil E. , Cerhan, James R. , Slager, Susan L.
Blood | April 19, 2018 | Volume: 131 | Issue: 23 | Pages: 2541-2551
Key Points PRS, based on the known CLL loci, predicts CLL risk with high discrimination. This PRS predicts risk of monoclonal B-cell lymphocytosis, a precursor to CLL and a condition that has clinical impact beyond risk for CLL.