A bidirectional Mendelian randomization study on the causal relationship between biochemical markers and pancreatic cancer
10.3760/cma.j.cn115667-20250208-00016
- VernacularTitle:生物化学标志物与胰腺癌因果关系的双向孟德尔随机化研究
- Author:
Yao WANG
1
;
Pu XU
1
;
Zhuo LI
1
Author Information
1. 西安医学院第一附属医院检验科，西安 710077
- Publication Type:Journal Article
- Keywords:
Biomarkers;
Pancreatic cancer;
Marker;
Bidirectional;
Mendelian randomization study
- From:
Chinese Journal of Pancreatology
2025;25(4):262-267
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the causal relationship between biochemical markers and pancreatic cancer using a two-sample Mendelian randomization (MR) approach.Methods:Genome-wide association study (GWAS) data were used to analyze the causal relationship between 35 blood and urine biochemical markers and pancreatic cancer by forward and reverse MR methods. Single nucleotide polymorphism (SNP) associated with exposure variables were used as instrumental variables. The inverse variance weighting method was adopted as the main analytical approach to investigate the causal relationship between exposure factors and outcomes. Meanwhile, MR-Egger method, weighted median method, simple mode method, and weighted mode method were used to enhance the robustness of the results. Additionally, pleiotropy, heterogeneity and sensitivity analyses were conducted to test the reliability of the results.Results:Forward MR screening identified that three blood biochemical markers (cholesterol, cystatin C, and sex hormone-binding globulin) had a positive causal relationship with pancreatic cancer. Cholesterol ( OR=2.361, 95% CI 1.299-4.292, P=0.005), cystatin C( OR=2.108, 95% CI 1.075-4.123, P=0.030), and sex hormone-binding globulin ( OR=1.927, 95% CI 1.031-3.600, P=0.040) were risk factors for pancreatic cancer. Reverse MR screening revealed that three blood biochemical markers (cholesterol, glycated hemoglobin, and sex hormone-binding globulin) had a negative causal relationship with pancreatic cancer. Pancreatic cancer was a protective factor for cholesterol ( OR=0.996, 95% CI 0.992-1.000, P=0.035) and glycated hemoglobin ( OR=0.995, 95% CI 0.991-0.999, P=0.013), while it was a risk factor for sex hormone-binding globulin ( OR=1.005, 95% CI 1.001-1.009, P=0.021). The trends of causal effects obtained by the inverse variance weighting method were basically consistent with those from MR-Egger method, weighted median method, simple mode method and weighted mode method. Pleiotropy, heterogeneity, and sensitivity analyses showed no evidence of pleiotropy or heterogeneity, and no SNP had a significant impact on the overall results. Conclusions:Cholesterol, glycated hemoglobin, and sex hormone-binding globulin are risk factors for pancreatic cancer. Pancreatic cancer is a protective factor for cholesterol and glycated hemoglobin, and a risk factor for sex hormone-binding globulin.
