Genetic susceptibility to nonalcoholic fatty liver disease and risk for pancreatic cancer: Mendelian Randomization

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.Data from genome-wide ass...

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Hauptverfasser: King, Sontoria (VerfasserIn) , Veliginti, Swathi (VerfasserIn) , Brouwers, Martijn C.G.J. (VerfasserIn) , Ren, Zhewen (VerfasserIn) , Zheng, Wei (VerfasserIn) , Setiawan, Veronica W. (VerfasserIn) , Wilkens, Lynne R. (VerfasserIn) , Shu, Xiao-Ou (VerfasserIn) , Arslan, Alan A. (VerfasserIn) , Beane Freeman, Laura E. (VerfasserIn) , Bracci, Paige M. (VerfasserIn) , Canzian, Federico (VerfasserIn) , Du, Mengmeng (VerfasserIn) , Gallinger, Steven J. (VerfasserIn) , Giles, Graham G. (VerfasserIn) , Goodman, Phyllis J. (VerfasserIn) , Haiman, Christopher A. (VerfasserIn) , Kogevinas, Manolis (VerfasserIn) , Kooperberg, Charles (VerfasserIn) , LeMarchand, Loic (VerfasserIn) , Neale, Rachel E. (VerfasserIn) , Visvanathan, Kala (VerfasserIn) , White, Emily (VerfasserIn) , Albanes, Demetrius (VerfasserIn) , Andreotti, Gabriella (VerfasserIn) , Babic, Ana (VerfasserIn) , Berndt, Sonja I. (VerfasserIn) , Brais, Lauren K. (VerfasserIn) , Brennan, Paul (VerfasserIn) , Buring, Julie E. (VerfasserIn) , Rabe, Kari G. (VerfasserIn) , Bamlet, William R. (VerfasserIn) , Chanock, Stephen J. (VerfasserIn) , Fuchs, Charles S. (VerfasserIn) , Gaziano, J. Michael (VerfasserIn) , Giovannucci, Edward L. (VerfasserIn) , Hackert, Thilo (VerfasserIn) , Hassan, Manal M. (VerfasserIn) , Katzke, Verena (VerfasserIn) , Kurtz, Robert C. (VerfasserIn) , Lee, I.-Min (VerfasserIn) , Malats, Núria (VerfasserIn) , Murphy, Neil (VerfasserIn) , Oberg, Ann L. (VerfasserIn) , Orlow, Irene (VerfasserIn) , Porta, Miquel (VerfasserIn) , Real, Francisco X. (VerfasserIn) , Rothman, Nathaniel (VerfasserIn) , Sesso, Howard D. (VerfasserIn) , Silverman, Debra T. (VerfasserIn) , Thompson, Ian M., Jr (VerfasserIn) , Wactawski-Wende, Jean (VerfasserIn) , Wang, Xiaoliang (VerfasserIn) , Wentzensen, Nicolas (VerfasserIn) , Yu, Herbert (VerfasserIn) , Zeleniuch-Jacquotte, Anne (VerfasserIn) , Yu, Kai (VerfasserIn) , Wolpin, Brian M. (VerfasserIn) , Duell, Eric J. (VerfasserIn) , Li, Donghui (VerfasserIn) , Hung, Rayjean J. (VerfasserIn) , Perdomo, Sandra (VerfasserIn) , McCullough, Marjorie L. (VerfasserIn) , Freedman, Neal D. (VerfasserIn) , Patel, Alpa V. (VerfasserIn) , Peters, Ulrike (VerfasserIn) , Riboli, Elio (VerfasserIn) , Sund, Malin (VerfasserIn) , Tjønneland, Anne (VerfasserIn) , Zhong, Jun (VerfasserIn) , Van Den Eeden, Stephen K. (VerfasserIn) , Kraft, Peter (VerfasserIn) , Risch, Harvey A. (VerfasserIn) , Amundadottir, Laufey T. (VerfasserIn) , Klein, Alison P. (VerfasserIn) , Stolzenberg-Solomon, Rachael Z. (VerfasserIn) , Antwi, Samuel O. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 1 September 2023
In: Cancer epidemiology, biomarkers & prevention
Year: 2023, Jahrgang: 32, Heft: 9, Pages: 1265-1269
ISSN:1538-7755
DOI:10.1158/1055-9965.EPI-23-0453
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1055-9965.EPI-23-0453
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Verfasserangaben:Sontoria D. King, Swathi Veliginti, Martijn C.G.J. Brouwers, Zhewen Ren, Wei Zheng, Veronica W. Setiawan, Lynne R. Wilkens, Xiao-Ou Shu, Alan A. Arslan, Laura E. Beane Freeman, Paige M. Bracci, Federico Canzian, Mengmeng Du, Steven J. Gallinger, Graham G. Giles, Phyllis J. Goodman, Christopher A. Haiman, Manolis Kogevinas, Charles Kooperberg, Loic LeMarchand, Rachel E. Neale, Kala Visvanathan, Emily White, Demetrius Albanes, Gabriella Andreotti, Ana Babic, Sonja I. Berndt, Lauren K. Brais, Paul Brennan, Julie E. Buring, Kari G. Rabe, William R. Bamlet, Stephen J. Chanock, Charles S. Fuchs, J. Michael Gaziano, Edward L. Giovannucci, Thilo Hackert, Manal M. Hassan, Verena Katzke, Robert C. Kurtz, I.-Min Lee, Núria Malats, Neil Murphy, Ann L. Oberg, Irene Orlow, Miquel Porta, Francisco X. Real, Nathaniel Rothman, Howard D. Sesso, Debra T. Silverman, Ian M., Jr Thompson, Jean Wactawski-Wende, Xiaoliang Wang, Nicolas Wentzensen, Herbert Yu, Anne Zeleniuch-Jacquotte, Kai Yu, Brian M. Wolpin, Eric J. Duell, Donghui Li, Rayjean J. Hung, Sandra Perdomo, Marjorie L. McCullough, Neal D. Freedman, Alpa V. Patel, Ulrike Peters, Elio Riboli, Malin Sund, Anne Tjønneland, Jun Zhong, Stephen K. Van Den Eeden, Peter Kraft, Harvey A. Risch, Laufey T. Amundadottir, Alison P. Klein, Rachael Z. Stolzenberg-Solomon, and Samuel O. Antwi

MARC

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245 1 0 |a Genetic susceptibility to nonalcoholic fatty liver disease and risk for pancreatic cancer  |b Mendelian Randomization  |c Sontoria D. King, Swathi Veliginti, Martijn C.G.J. Brouwers, Zhewen Ren, Wei Zheng, Veronica W. Setiawan, Lynne R. Wilkens, Xiao-Ou Shu, Alan A. Arslan, Laura E. Beane Freeman, Paige M. Bracci, Federico Canzian, Mengmeng Du, Steven J. Gallinger, Graham G. Giles, Phyllis J. Goodman, Christopher A. Haiman, Manolis Kogevinas, Charles Kooperberg, Loic LeMarchand, Rachel E. Neale, Kala Visvanathan, Emily White, Demetrius Albanes, Gabriella Andreotti, Ana Babic, Sonja I. Berndt, Lauren K. Brais, Paul Brennan, Julie E. Buring, Kari G. Rabe, William R. Bamlet, Stephen J. Chanock, Charles S. Fuchs, J. Michael Gaziano, Edward L. Giovannucci, Thilo Hackert, Manal M. Hassan, Verena Katzke, Robert C. Kurtz, I.-Min Lee, Núria Malats, Neil Murphy, Ann L. Oberg, Irene Orlow, Miquel Porta, Francisco X. Real, Nathaniel Rothman, Howard D. Sesso, Debra T. Silverman, Ian M., Jr Thompson, Jean Wactawski-Wende, Xiaoliang Wang, Nicolas Wentzensen, Herbert Yu, Anne Zeleniuch-Jacquotte, Kai Yu, Brian M. Wolpin, Eric J. Duell, Donghui Li, Rayjean J. Hung, Sandra Perdomo, Marjorie L. McCullough, Neal D. Freedman, Alpa V. Patel, Ulrike Peters, Elio Riboli, Malin Sund, Anne Tjønneland, Jun Zhong, Stephen K. Van Den Eeden, Peter Kraft, Harvey A. Risch, Laufey T. Amundadottir, Alison P. Klein, Rachael Z. Stolzenberg-Solomon, and Samuel O. Antwi 
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520 |a 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.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.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.Genetic predisposition to NAFLD is not associated with pancreatic cancer risk.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. 
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700 1 |a Brouwers, Martijn C.G.J.  |e VerfasserIn  |4 aut 
700 1 |a Ren, Zhewen  |e VerfasserIn  |4 aut 
700 1 |a Zheng, Wei  |e VerfasserIn  |4 aut 
700 1 |a Setiawan, Veronica W.  |e VerfasserIn  |4 aut 
700 1 |a Wilkens, Lynne R.  |e VerfasserIn  |4 aut 
700 1 |a Shu, Xiao-Ou  |e VerfasserIn  |4 aut 
700 1 |a Arslan, Alan A.  |e VerfasserIn  |4 aut 
700 1 |a Beane Freeman, Laura E.  |e VerfasserIn  |4 aut 
700 1 |a Bracci, Paige M.  |e VerfasserIn  |4 aut 
700 1 |a Canzian, Federico  |e VerfasserIn  |0 (DE-588)118890468X  |0 (DE-627)1667771264  |4 aut 
700 1 |a Du, Mengmeng  |e VerfasserIn  |4 aut 
700 1 |a Gallinger, Steven J.  |e VerfasserIn  |4 aut 
700 1 |a Giles, Graham G.  |e VerfasserIn  |4 aut 
700 1 |a Goodman, Phyllis J.  |e VerfasserIn  |4 aut 
700 1 |a Haiman, Christopher A.  |e VerfasserIn  |4 aut 
700 1 |a Kogevinas, Manolis  |e VerfasserIn  |4 aut 
700 1 |a Kooperberg, Charles  |e VerfasserIn  |4 aut 
700 1 |a LeMarchand, Loic  |e VerfasserIn  |4 aut 
700 1 |a Neale, Rachel E.  |e VerfasserIn  |4 aut 
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700 1 |a Brais, Lauren K.  |e VerfasserIn  |4 aut 
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700 1 |a Rabe, Kari G.  |e VerfasserIn  |4 aut 
700 1 |a Bamlet, William R.  |e VerfasserIn  |4 aut 
700 1 |a Chanock, Stephen J.  |e VerfasserIn  |4 aut 
700 1 |a Fuchs, Charles S.  |e VerfasserIn  |4 aut 
700 1 |a Gaziano, J. Michael  |e VerfasserIn  |4 aut 
700 1 |a Giovannucci, Edward L.  |e VerfasserIn  |4 aut 
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700 1 |a Katzke, Verena  |e VerfasserIn  |4 aut 
700 1 |a Kurtz, Robert C.  |e VerfasserIn  |4 aut 
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700 1 |a Silverman, Debra T.  |e VerfasserIn  |4 aut 
700 1 |a Thompson, Ian M., Jr  |e VerfasserIn  |4 aut 
700 1 |a Wactawski-Wende, Jean  |e VerfasserIn  |4 aut 
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700 1 |a Zhong, Jun  |e VerfasserIn  |4 aut 
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