Mendelian randomisation study of the effects of known and putative risk factors on pancreatic cancer.
Adenocarcinoma
/ genetics
Adult
Aged
Body Mass Index
Carcinoma, Pancreatic Ductal
/ complications
Diabetes Mellitus, Type 2
/ complications
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Helicobacter Infections
/ complications
Humans
Insulin
/ genetics
Male
Mendelian Randomization Analysis
Middle Aged
Obesity
/ complications
Polymorphism, Single Nucleotide
/ genetics
Risk Factors
Mendelian randomization
genetic polymorphisms
pancreatic cancer
risk factors
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
04
04
2019
revised:
13
01
2020
accepted:
15
01
2020
pubmed:
19
2
2020
medline:
6
7
2021
entrez:
19
2
2020
Statut:
ppublish
Résumé
Observational studies have reported multiple risk factors for pancreatic ductal adenocarcinoma (PDAC). Some are well established, like tobacco smoking, alcohol drinking, obesity and type 2 diabetes, whereas some others are putative, such as allergy and dietary factors. Identifying causal risk factors can help establishing those that can be targeted to contribute to prevent PDAC. We sought to investigate the possible causal effects of established and putative factors on PDAC risk. We conducted a two-sample Mendelian randomisation (MR) study using publicly available data for genetic variants associated with the factors of interest, and summary genetic data from genome-wide association studies of the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including in total 8769 cases and 7055 controls. Causality was assessed using inverse-variance weighted, MR-Egger regression and weighted median methods, complemented with sensitivity and radial MR analyses. We found evidence for a causal effect of body mass index (BMI) on PDAC risk (OR 1.43, 95% CI 1.20 to 1.71, p=8.43×10 We found strong evidence that BMI is causally associated with PDAC risk, providing support that obesity management may be a potential prevention strategy for reducing pancreatic cancer risk while fasting insulin and type 2 diabetes showed a suggestive association that should be further investigated.
Sections du résumé
BACKGROUND
Observational studies have reported multiple risk factors for pancreatic ductal adenocarcinoma (PDAC). Some are well established, like tobacco smoking, alcohol drinking, obesity and type 2 diabetes, whereas some others are putative, such as allergy and dietary factors. Identifying causal risk factors can help establishing those that can be targeted to contribute to prevent PDAC.
OBJECTIVE
We sought to investigate the possible causal effects of established and putative factors on PDAC risk.
METHODS
We conducted a two-sample Mendelian randomisation (MR) study using publicly available data for genetic variants associated with the factors of interest, and summary genetic data from genome-wide association studies of the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including in total 8769 cases and 7055 controls. Causality was assessed using inverse-variance weighted, MR-Egger regression and weighted median methods, complemented with sensitivity and radial MR analyses.
RESULTS
We found evidence for a causal effect of body mass index (BMI) on PDAC risk (OR 1.43, 95% CI 1.20 to 1.71, p=8.43×10
CONCLUSION
We found strong evidence that BMI is causally associated with PDAC risk, providing support that obesity management may be a potential prevention strategy for reducing pancreatic cancer risk while fasting insulin and type 2 diabetes showed a suggestive association that should be further investigated.
Identifiants
pubmed: 32066631
pii: jmedgenet-2019-106200
doi: 10.1136/jmedgenet-2019-106200
doi:
Substances chimiques
Insulin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
820-828Informations de copyright
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.