Buring, Julie E
Mayo Clinic
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
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.
Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization
King, Sontoria D. , Veliginti, Swathi , Brouwers, Martijn C.G.J. , Ren, Zhewen , Zheng, Wei , Setiawan, Veronica Wendy , Wilkens, Lynne R. , Shu, Xiao‐Ou , Arslan, Alan A. , Freeman, Laura E. Beane , Bracci, Paige M. , Du, Mengmeng , Gallinger, Steven , Goodman, Phyllis J. , Haiman, Christopher A. , Visvanathan, Kala , White, Emily , Andreotti, Gabriella , Babić, Ana , Berndt, Sonja I. , Brennan, Paul , Buring, Julie E. , Fuchs, Charles S. , Gaziano, J. Michael , Giovannucci, Edward L. , Hackert, Thilo , Hassan, Manal M. , Kurtz, Robert C. , Lee, I‐Min , Oberg, Ann L. , Porta, Miquel , Rothman, Nathaniel , Sesso, Howard D. , Wentzensen, Nicolas , Yu, Kai , Wolpin, Brian M. , Li, Donghui , Patel, Alpa V. , Peters, Ulrike , Ríboli, Elio , Zhong, Jun, Antwi, Samuel O. , Zhong, Jun , Setiawan, Veronica W , Beane Freeman, Laura E , Canzian, Federico , Du, Mengmeng , Gallinger, Steven , Giles, Graham G , Goodman, Phyllis J , Haiman, Christopher A , Kogevinas, Manolis , Kooperberg, Charles , Marchand, Loïc Le , Neale, Rachel E , Visvanathan, Kala , White, Emily , Albanes, Demetrius , Andreotti, Gabriella , Babic, Ana , Berndt, Sonja I , Brais, Lauren K , Brennan, Paul , Buring, Julie E , Chaffee, Kari G. , Bamlet, William R , Chanock, Stephen Jacob , Fuchs, Charles S , Gaziano, J Michael , Giovannucci, Edward L , Hackert, Thilo , Hassan, Manal M , Katzke, Verena , Kurtz, Robert C , Lee, I-Min , Malats, Nuria , Murphy, Neil , Oberg, Ann L , Orlow, Irene , Porta, Miquel , Real, Francisco X , Rothman, Nathaniel , Sesso, Howard D , Silverman, Debra T. , Thompson, Ian M , Wactawski-Wende, Jean , Wang, Xiaoliang , Wentzensen, Nicolas , Yu, Herbert , Zeleniuch-Jacquotte, Anne , Yu, Kai , Wolpin, Brian M , Duell, Eric J , Li, Donghui , Hung, Rayjean J , Perdomo, Sandra , McCullough, Marjorie L , Freedman, Neal D , Patel, Alpa V , Peters, Ulrike , Riboli, Elio , Sund, Malin , Tjønneland, Anne , Zhong, Jun , Van Den Eeden, Stephen K , Kraft, Peter , Risch, Harvey A , Amundadottir, Laufey , Klein, Alison P , Stolzenberg-Solomon, Rachael , Antwi, Samuel O , Arslan, Alan A , Shu, Xiao-Ou , Zheng, Wei , Wilkens, Lynne R , Canzian, Federico , Giles, Graham G. , Kooperberg, Charles , Marchand, Loı̈c Le , Neale, Rachel Ε. , Albanes, Demetrius , Rabe, Kari G. , Bamlet, William R. , Malats, Núria , Murphy, Neil , Orlow, Irene , Real, Francisco X. , Thompson, Ian M. , Wactawski‐Wende, Jean , Wang, Xiaoliang , Yu, Kai , Zeleniuch‐Jacquotte, Anne , Duell, Eric J. , Hung, Rayjean J. , McCullough, Marjorie L. , Freedman, Neal D. , Sund, Malin , Tjønneland, Anne , Kraft, Peter , Risch, Harvey A. , Ámundadóttir, Laufey T. , Klein, Alison P. , Stolzenberg‐Solomon, Rachael Z.
Cancer Epidemiology, Biomarkers & Prevention | June 24, 2023 | Volume: 32 | Issue: 9 | Pages: 1265-1269
Abstract Background: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer. Methods: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes. Results: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88–1.22; MR-Egger OR, 0.89; 95% CI, 0.65–1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90–1.27; MR-Egger OR, 0.93; 95% CI, 0.67–1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample. Conclusions: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk. Impact: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.