Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization

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 Babie; 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. 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; Samuel O. Antwi

doi:10.1158/1055-9965.EPI-23-0453

Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization

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 LeMarchandRachel E. Neale, Kala Visvanathan, Emily White, Demetrius Albanes, Gabriella Andreotti, Ana Babie, 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. 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, Samuel O. Antwi

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Abstract

Background: There are conflicting dataon 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 ¼ 5,090, controls n ¼ 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n ¼ 4,163, controls n ¼ 3,792) were analyzed.Weused dataon68genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separatelyto predict genetic heritability of NAFLD. We then assessed the relationship between eachofthe fourMRmethods andpancreatic 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.

Original language	English (US)
Pages (from-to)	1265-1269
Number of pages	5
Journal	Cancer Epidemiology Biomarkers and Prevention
Volume	32
Issue number	9
DOIs	https://doi.org/10.1158/1055-9965.EPI-23-0453
State	Published - Sep 1 2023

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General Medicine

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King, S. D., Veliginti, S., Brouwers, M. C. G. J., Ren, Z., Zheng, W., Setiawan, V. W., Wilkens, L. R., Shu, X. O., Arslan, A. A., Beane Freeman, L. E., Bracci, P. M., Canzian, F., Du, M., Gallinger, S. J., Giles, G. G., Goodman, P. J., Haiman, C. A., Kogevinas, M., Kooperberg, C., ... Antwi, S. O. (2023). Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization. Cancer Epidemiology Biomarkers and Prevention, 32(9), 1265-1269. https://doi.org/10.1158/1055-9965.EPI-23-0453

King, SD, Veliginti, S, Brouwers, MCGJ, Ren, Z, Zheng, W, Setiawan, VW, Wilkens, LR, Shu, XO, Arslan, AA, Beane Freeman, LE, Bracci, PM, Canzian, F, Du, M, Gallinger, SJ, Giles, GG, Goodman, PJ, Haiman, CA, Kogevinas, M, Kooperberg, C, LeMarchand, L, Neale, RE, Visvanathan, K, White, E, Albanes, D, Andreotti, G, Babie, A, Berndt, SI, Brais, LK, Brennan, P, Buring, JE, Rabe, KG, Bamlet, WR, Chanock, SJ, Fuchs, CS, Gaziano, JM, Giovannucci, EL, Hackert, T, Hassan, MM, Katzke, V, Kurtz, RC, Lee, IM, Malats, N, Murphy, N, Oberg, AL, Orlow, I, Porta, M, Real, FX, Rothman, N, Sesso, HD, Silverman, DT, Thompson, IM, Wactawski-Wende, J, Wang, X, Wentzensen, N, Yu, H, Zeleniuch-Jacquotte, A, Yu, K, Wolpin, BM, Duell, EJ, Li, D, Hung, RJ, Perdomo, S, McCullough, ML, Freedman, ND, Patel, AV, Peters, U, Riboli, E, Sund, M, Tjønneland, A, Zhong, J, Van Den Eeden, SK, Kraft, P, Risch, HA, Amundadottir, LT, Klein, AP, Stolzenberg-Solomon, RZ & Antwi, SO 2023, 'Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization', Cancer Epidemiology Biomarkers and Prevention, vol. 32, no. 9, pp. 1265-1269. https://doi.org/10.1158/1055-9965.EPI-23-0453

@article{2741fa5444e844c585d97400b532cb87,

title = "Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization",

abstract = "Background: There are conflicting dataon 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 ¼ 5,090, controls n ¼ 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n ¼ 4,163, controls n ¼ 3,792) were analyzed.Weused dataon68genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separatelyto predict genetic heritability of NAFLD. We then assessed the relationship between eachofthe fourMRmethods andpancreatic 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.",

author = "King, {Sontoria D.} and Swathi Veliginti and Brouwers, {Martijn C.G.J.} and Zhewen Ren and Wei Zheng and Setiawan, {Veronica W.} and Wilkens, {Lynne R.} and Shu, {Xiao Ou} and Arslan, {Alan A.} and {Beane Freeman}, {Laura E.} and Bracci, {Paige M.} and Federico Canzian and Mengmeng Du and Gallinger, {Steven J.} and Giles, {Graham G.} and Goodman, {Phyllis J.} and Haiman, {Christopher A.} and Manolis Kogevinas and Charles Kooperberg and Loic LeMarchand and Neale, {Rachel E.} and Kala Visvanathan and Emily White and Demetrius Albanes and Gabriella Andreotti and Ana Babie and Berndt, {Sonja I.} and Brais, {Lauren K.} and Paul Brennan and Buring, {Julie E.} and Rabe, {Kari G.} and Bamlet, {William R.} and Chanock, {Stephen J.} and Fuchs, {Charles S.} and Gaziano, {J. Michael} and Giovannucci, {Edward L.} and Thilo Hackert and Hassan, {Manal M.} and Verena Katzke and Kurtz, {Robert C.} and Lee, {I. Min} and N{\'u}ria Malats and Neil Murphy and Oberg, {Ann L.} and Irene Orlow and Miquel Porta and Real, {Francisco X.} and Nathaniel Rothman and Sesso, {Howard D.} and Silverman, {Debra T.} and Thompson, {Ian M.} and Jean Wactawski-Wende and Xiaoliang Wang and Nicolas Wentzensen and Herbert Yu and Anne Zeleniuch-Jacquotte and Kai Yu and Wolpin, {Brian M.} and Duell, {Eric J.} and Donghui Li and Hung, {Rayjean J.} and Sandra Perdomo and McCullough, {Marjorie L.} and Freedman, {Neal D.} and Patel, {Alpa V.} and Ulrike Peters and Elio Riboli and Malin Sund and Anne Tj{\o}nneland and Jun Zhong and {Van Den Eeden}, {Stephen K.} and Peter Kraft and Risch, {Harvey A.} and Amundadottir, {Laufey T.} and Klein, {Alison P.} and Stolzenberg-Solomon, {Rachael Z.} and Antwi, {Samuel O.}",

year = "2023",

month = sep,

day = "1",

doi = "10.1158/1055-9965.EPI-23-0453",

language = "English (US)",

volume = "32",

pages = "1265--1269",

journal = "Cancer Epidemiology Biomarkers and Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "9",

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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 W.

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 - LeMarchand, Loic

AU - Neale, Rachel E.

AU - Visvanathan, Kala

AU - White, Emily

AU - Albanes, Demetrius

AU - Andreotti, Gabriella

AU - Babie, 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, Núria

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 - Thompson, Ian M.

AU - Wactawski-Wende, Jean

AU - Wang, Xiaoliang

AU - Wentzensen, Nicolas

AU - Yu, Herbert

AU - Zeleniuch-Jacquotte, Anne

AU - Yu, Kai

AU - Wolpin, Brian M.

AU - Duell, Eric J.

AU - Li, Donghui

AU - Hung, Rayjean J.

AU - Perdomo, Sandra

AU - McCullough, Marjorie L.

AU - Freedman, Neal D.

AU - Patel, Alpa V.

AU - Peters, Ulrike

AU - Riboli, Elio

AU - Sund, Malin

AU - Tjønneland, Anne

AU - Zhong, Jun

AU - Van Den Eeden, Stephen K.

AU - Kraft, Peter

AU - Risch, Harvey A.

AU - Amundadottir, Laufey T.

AU - Klein, Alison P.

AU - Stolzenberg-Solomon, Rachael Z.

AU - Antwi, Samuel O.

PY - 2023/9/1

Y1 - 2023/9/1

N2 - Background: There are conflicting dataon 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 ¼ 5,090, controls n ¼ 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n ¼ 4,163, controls n ¼ 3,792) were analyzed.Weused dataon68genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separatelyto predict genetic heritability of NAFLD. We then assessed the relationship between eachofthe fourMRmethods andpancreatic 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.

AB - Background: There are conflicting dataon 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 ¼ 5,090, controls n ¼ 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n ¼ 4,163, controls n ¼ 3,792) were analyzed.Weused dataon68genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separatelyto predict genetic heritability of NAFLD. We then assessed the relationship between eachofthe fourMRmethods andpancreatic 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=85169503652&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-23-0453

DO - 10.1158/1055-9965.EPI-23-0453

M3 - Article

C2 - 37351909

AN - SCOPUS:85169503652

SN - 1055-9965

VL - 32

SP - 1265

EP - 1269

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

IS - 9

ER -

Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization

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