TY - JOUR
T1 - Genetic susceptibility to nonalcoholic fatty liver disease and risk for pancreatic cancer
T2 - Mendelian randomization
AU - King, Sontoria D
AU - Veliginti, Swathi
AU - Brouwers, Martijn C G J
AU - Ren, Zhewen
AU - Zheng, Wei
AU - Setiawan, Veronica Wendy
AU - Wilkens, Lynne R
AU - Shu, Xiao-Ou
AU - Arslan, Alan A
AU - Beane Freeman, Laura E
AU - Bracci, Paige M
AU - Canzian, Federico
AU - Du, Mengmeng
AU - Gallinger, Steven J
AU - Giles, Graham G
AU - Goodman, Phyllis J
AU - Haiman, Christopher A
AU - Kogevinas, Manolis
AU - Kooperberg, Charles
AU - Le Marchand, Loic
AU - Neale, Rachel E
AU - Visvanathan, Kala
AU - White, Emily
AU - Albanes, Demetrius
AU - Andreotti, Gabriella
AU - Babic, Ana
AU - Berndt, Sonja I
AU - Brais, Lauren K
AU - Brennan, Paul
AU - Buring, Julie E
AU - Rabe, Kari G
AU - Bamlet, William R
AU - Chanock, Stephen J
AU - Fuchs, Charles S
AU - Gaziano, J Michael
AU - Giovannucci, Edward L
AU - Hackert, Thilo
AU - Hassan, Manal M
AU - Katzke, Verena
AU - Kurtz, Robert C
AU - Lee, I-Min
AU - Malats, Nuria
AU - Murphy, Neil
AU - Oberg, Ann L
AU - Orlow, Irene
AU - Porta, Miquel
AU - Real, Francisco X
AU - Rothman, Nathaniel
AU - Sesso, Howard D
AU - Silverman, Debra T
AU - Antwi, Samuel O.
AU - Et al.
PY - 2023/9
Y1 - 2023/9
N2 - BACKGROUND: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer (PC). Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for PC. METHODS: Data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium (PanScan; cases n=5090, controls n=8733) 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 PC risk, using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for PC risk factors, including obesity and diabetes. RESULTS: No association was found between genetically predicted NAFLD and PC risk in the PanScan or PanC4 samples (e.g., PanScan, IVW OR=1.04, 95% 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 PC risk in either sample. CONCLUSIONS: Genetic predisposition to NAFLD is not associated with PC risk. IMPACT: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and PC might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and PC.
AB - BACKGROUND: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer (PC). Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for PC. METHODS: Data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium (PanScan; cases n=5090, controls n=8733) 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 PC risk, using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for PC risk factors, including obesity and diabetes. RESULTS: No association was found between genetically predicted NAFLD and PC risk in the PanScan or PanC4 samples (e.g., PanScan, IVW OR=1.04, 95% 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 PC risk in either sample. CONCLUSIONS: Genetic predisposition to NAFLD is not associated with PC risk. IMPACT: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and PC might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and PC.
U2 - 10.1158/1055-9965.EPI-23-0453
DO - 10.1158/1055-9965.EPI-23-0453
M3 - Article
SN - 1055-9965
VL - 32
SP - 1265
EP - 1269
JO - Cancer Epidemiology Biomarkers & Prevention
JF - Cancer Epidemiology Biomarkers & Prevention
IS - 9
ER -