Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization.
Journal
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608
Informations de publication
Date de publication:
01 09 2023
01 09 2023
Historique:
received:
25
04
2023
revised:
15
06
2023
accepted:
16
06
2023
pmc-release:
01
03
2024
medline:
4
9
2023
pubmed:
23
6
2023
entrez:
23
6
2023
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 37351909
pii: 727459
doi: 10.1158/1055-9965.EPI-23-0453
pmc: PMC10529823
mid: NIHMS1913245
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1265-1269Subventions
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL043851
Pays : United States
Organisme : NCI NIH HHS
ID : L30 CA209733
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA047988
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL080467
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA182913
Pays : United States
Organisme : NHLBI NIH HHS
ID : RC1 HL099355
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015083
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA182913
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA154823
Pays : United States
Organisme : NCI NIH HHS
ID : K01 CA237875
Pays : United States
Informations de copyright
©2023 American Association for Cancer Research.
Références
J Hepatol. 2017 Nov 02;:
pubmed: 29150142
Genet Epidemiol. 2020 Jun;44(4):313-329
pubmed: 32249995
J Hepatol. 2019 Dec;71(6):1229-1236
pubmed: 31470068
Nat Commun. 2018 Feb 8;9(1):556
pubmed: 29422604
Gastroenterology. 2015 Dec;149(7):1784-93
pubmed: 26299412
Gastroenterology. 2020 May;158(7):1851-1864
pubmed: 32061595
Nat Genet. 2022 Jun;54(6):761-771
pubmed: 35654975
Nat Med. 2018 Jul;24(7):908-922
pubmed: 29967350