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Updated: Jun 30, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Mendelian randomization analysis of metabolic blood biomarkers and gastrointestinal cancer risk
Xiufeng Huang1, Jianxin Chen1, Feiteng Gu1
1Second Department of Gastrointestinal Surgery, The Affiliated Hospital of Putian University, China.
Background:
Gastrointestinal (GI) cancers remain among the most lethal malignancies worldwide, highlighting the need for novel insights into modifiable risk factors. Blood-based metabolic biomarkers - routinely measured in clinical settings - may play a role in cancer etiology, but their causal impact remains unclear.
Objectives:
This study aimed to explore the causal relationship between metabolic blood biomarkers and the risk of GI cancers using Mendelian randomization (MR).
Material And Methods:
We conducted an MR analysis using large-scale genome-wide association study (GWAS) data to evaluate the causal effects of metabolic blood traits (e.g., low-density lipoprotein (LDL) cholesterol, creatinine, uric acid, total protein, and total cholesterol) on the risk of 4 major GI cancers: gastric, colorectal, pancreatic, and gallbladder cancer. Statistical robustness was evaluated using the MR-PRESSO test and Cochran's Q test.
Results:
Mendelian randomization analysis revealed several significant associations. Low-density lipoprotein cholesterol was inversely associated with gastric cancer risk (odds ratio (OR) = 0.815, 95% confidence interval (95% CI): 0.703-0.946, p < 0.01), while total cholesterol also showed a protective effect (OR = 0.790, 95% CI: 0.693-0.900, p < 0.01). Serum creatinine levels were strongly associated with a reduced risk of gallbladder cancer (OR = 0.037, 95% CI: 0.005-0.287, p < 0.01). Higher serum total protein (OR = 0.855, 95% CI: 0.777-0.940, p < 0.01) and uric acid levels (OR = 0.855, 95% CI: 0.769-0.951, p < 0.01) were associated with a reduced risk of colorectal cancer (CRC). Serum uric acid levels were also associated with a reduced risk of gastric cancer (OR = 0.822, 95% CI: 0.719-0.941, p < 0.01), but with an increased risk of pancreatic cancer (OR = 1.246, 95% CI: 1.01-1.539, p = 0.040).
Conclusions:
Our findings provide causal evidence linking common metabolic blood biomarkers to site-specific GI cancer risks. These results may inform biomarker-based risk stratification and preventive strategies in oncology and public health.