Otherindependent cross-checkabstract checked I-ORG-131 standard review
Genetic test of gallbladder removal and bowel cancer
Associations of cholecystectomy with the risk of colorectal cancer: a Mendelian randomization study.
Overview
Chen L et al.. Chin Med J (Engl) 2023 · PMID 37027252 · DOI 10.1097/CM9.0000000000002612
A genetic analysis found no sign that gallbladder removal itself causes bowel cancer, but gallstone disease might.
Does the study support the specific claim? No · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Use genetics to test causality
- How was the study done?
Mendelian randomisation
- How many people, animals or samples were studied?
Large genetic datasets
- What was actually found?
No causal effect of cholecystectomy on CRC
- How large was the observed effect?
OR 1.54 (0.61-3.92)
- What do the results mean in everyday life?
Gallstones, not the operation, may explain links
- What are the study's limitations?
Weak instruments, wide CIs
- What does it say about Elawady's specific claim?
Contradicts causal claim
- Do the results apply to Germany and Europe?
Applicable
- What can explicitly not be concluded from this study?
Not definitive
Scientific in-depth review
1. Full reference
- Authors
- Chen L et al.
- Journal
- Chin Med J (Engl)
- Year
- 2023
- Identifier
- PMID 37027252 DOI 10.1097/CM9.0000000000002612
- Verification
- verified – PubMed efetch 2026-10-26; Crossref works API 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Not stated in abstract.
2. Research question
Does genetic liability to cholecystectomy causally affect CRC and other outcomes, independent of cholelithiasis?
3. Study design and population
- Study design
- Other – Two-sample and multivariable Mendelian randomisation study
- Population
GWAS summary data
- Country
Multinational (GWAS consortia)
- Period
Not applicable
- Sample size
GWAS summary statistics (instruments explain 1.76% of variance)
- Inclusion and exclusion criteria
Genome-wide significant variants
4. Methods and endpoints
- Exposure / intervention
Genetic liability to cholecystectomy; cholelithiasis
- Comparator
n/a
- Endpoints
CRC, colon, rectal cancer; other outcomes
- Statistical methods
MR (OR per genetic liability)
5. Actual results
- Results
Cholecystectomy not associated with CRC (OR 1.543, 95% CI 0.607-3.924), nor colon or rectal cancer. Cholelithiasis liability increased CRC risk (OR 1.041, 1.010-1.073), also after adjustment for cholecystectomy (OR 1.061, 1.002-1.125). Possible increase in IBS (OR 7.573, 1.096-52.318).
- Absolute risks
Not applicable
- Authors' conclusion
Cholecystectomy might not increase CRC risk; gallstone liability may; needs further proof.
6. Strengths
- MR reduces confounding
- Separates gallstones from surgery
7. Weaknesses
- Weak instruments (1.76% variance)
- Very wide CIs
- Genetic liability to surgery is an unusual exposure
8. Risk of bias
- Orienting tool
- none applicable
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
MR assumptions (pleiotropy, instrument strength) are a concern.
9. Assessment of the statistical interpretation
Imprecise null for surgery; suggests gallstone disease rather than surgery may drive observational associations.
10. Relevance to the specific claim
Tests causality for the cholecystectomy-cancer association.
11. Independent contrary findings
Observational right-colon signals (I-ORG-129, A-ORG-06).
12. Transferability to Germany and Europe
Mostly European-ancestry GWAS.
13. Overall methodological judgement
Weak but relevant argument against a causal effect of cholecystectomy on CRC.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | low |
| Directness | indirect |
| Reproducibility | unknown |
| Consistency with the overall evidence | mixed |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Better-powered MR.
15. Linked fact checks
- Cholecystectomy causes a persistent long-term excess of proximal small-bowel adenocarcinoma and right-sided colon cancer (Lagergren 2001). – Studies contradicting or limiting the claim
- Long-term registry data link removal of tonsils, appendix, gallbladder, uterus, ovaries and spleen to higher rates of respiratory disease, autoimmunity, cardiovascular events, gastrointestinal cancers and dementia; each organ does work the body never fully replaces. – Studies contradicting or limiting the claim