Gallbladder disease and colorectal cancer: a two-sample bidirectional Mendelian randomization study.

Area of Science:

• Genetics
• Gastroenterology
• Oncology

Background:

• Gallbladder disease and colorectal cancer (CRC) are significant health concerns.
• Understanding potential causal relationships is crucial for risk stratification and prevention.

Purpose of the Study:

• To investigate a potential bidirectional causal relationship between gallbladder disease and colorectal cancer (CRC).
• Utilized a two-sample, bidirectional Mendelian randomization (MR) approach with genome-wide association study (GWAS) summary statistics.

Main Methods:

• Employed European-ancestry GWAS data from the UK Biobank.
• Conducted forward (gallbladder disease as exposure) and reverse (CRC as exposure) MR analyses.
• Applied inverse variance weighted (IVW) as the primary method, with sensitivity analyses including MR-Egger and heterogeneity/pleiotropy tests.

Main Results:

• Forward MR: No significant causal association found between gallbladder disease and CRC risk (P > 0.05).
• Reverse MR: No significant causal effect of genetic liability to CRC on gallbladder disease risk was detected (P > 0.05).
• Sensitivity analyses confirmed the robustness of findings, with no substantial horizontal pleiotropy or heterogeneity.

Conclusions:

• This study provides no evidence for a causal relationship between gallbladder disease and CRC in either direction.
• Gallbladder disease and its genetic susceptibility are unlikely to be major genetic drivers of colorectal carcinogenesis.
• Individuals with gallbladder disease history should not be solely classified as high-risk for CRC, but metabolic factors require management.