Mendelian randomization analysis reveals genetic associations between pancreatic cancer and its risk factors
10.3760/cma.j.cn113884-20250305-00074
- VernacularTitle:孟德尔随机化分析揭示胰腺癌与其危险因素的遗传关联
- Author:
Shuang LI
1
;
Ben LIU
1
;
Wei XIANG
1
;
An YAN
1
;
Wenzhe GAO
1
;
Hongwei ZHU
1
;
Xiao YU
1
Author Information
1. 中南大学湘雅三医院肝胆胰外科，长沙 410013
- Publication Type:Journal Article
- Keywords:
Pancreatic neoplasms;
Risk factors;
Mendelian randomization
- From:
Chinese Journal of Hepatobiliary Surgery
2025;31(10):762-767
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To clarify the genetic associations between obesity, diabetes, smoking, non-alcoholic fatty liver disease, acute and chronic pancreatitis, and pancreatic cancer risk.Methods:Summary data from genome-wide association studies (GWAS) of individuals of European descent were used. Obesity, alcohol consumption, diabetes, and acute and chronic pancreatitis data for the UK population were obtained from the GWAS catalog, while alcohol consumption, non-alcoholic fatty liver disease, occasional smoking, and regular smoking data were obtained from the UK biobank. Pancreatic cancer-related data for the Finnish population were sourced from the latest R11 version of the Finnish database. Two-sample Mendelian randomization (MR) analysis was conducted on the associations between the aforementioned risk factors and pancreatic cancer using five MR methods, primarily inverse variance weighting. The robustness of the results was assessed through Q heterogeneity tests, pleiotropy tests, MR-PRESSO analysis, and reverse MR analysis.Results:Obesity showed a significant positive association with pancreatic cancer risk ( OR=1.407, 95% CI: 1.100-1.714, P=0.030), and the results were robust based on Q heterogeneity tests, pleiotropy tests, MR-PRESSO, and reverse MR analysis (all P>0.05). However, no significant associations were found between pancreatic cancer risk and alcohol consumption ( P=0.330), heavy drinking ( P=0.382), type 1 diabetes ( P=0.674), type 2 diabetes ( P=0.825), occasional smoking ( P=0.607), regular smoking ( P=0.758), non-alcoholic fatty liver disease ( P=0.287), acute pancreatitis ( P=0.336), or chronic pancreatitis ( P=0.545). Conclusion:This study further confirms the strong genetic association between obesity and increased pancreatic cancer risk.
