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Hepatobiliary Malignancies
Risk factors for intrahepatic cholangiocarcinoma: Association between metformin use and reduced cancer risk†‡
Article first published online: 12 DEC 2012
DOI: 10.1002/hep.26092
Copyright © 2012 American Association for the Study of Liver Diseases
Additional Information
How to Cite
Chaiteerakij, R., Yang, J. D., Harmsen, W. S., Slettedahl, S. W., Mettler, T. A., Fredericksen, Z. S., Kim, W. R., Gores, G. J., Roberts, R. O., Olson, J. E., Therneau, T. M. and Roberts, L. R. (2013), Risk factors for intrahepatic cholangiocarcinoma: Association between metformin use and reduced cancer risk. Hepatology, 57: 648–655. doi: 10.1002/hep.26092
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Potential conflict of interest: Nothing to report.
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This work was supported by the National Institutes of Health (grant nos.: CA100882, CA128633, and CA165076), the Mayo Clinic Center for Cell Signaling in Gastroenterology (NIDDK P30DK084567), the Mayo Clinic Cancer Center (CA15083), and the Mayo Foundation (to L.R.R.).
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Publication History
- Issue published online: 5 FEB 2013
- Article first published online: 12 DEC 2012
- Accepted manuscript online: 11 OCT 2012 01:30AM EST
- Manuscript Accepted: 24 SEP 2012
- Manuscript Received: 17 JUN 2012
Abstract
The associations between diabetes, smoking, obesity, and intrahepatic cholangiocarcinoma (ICC) risk remain inconclusive. Metformin is purportedly associated with a reduced risk for various cancers. This case-control study evaluated risk factors for ICC and explored the effects of metformin on ICC risk in a clinic/hospital-based cohort. ICC patients observed at the Mayo Clinic (Rochester, MN) between January 2000 and May 2010 were identified. Age, sex, ethnicity, and residential area-matched controls were selected from among Mayo Clinic Biobank participants. The associations between potential factors and ICC risk were determined. Six hundred and twelve cases and 594 controls were identified. Factors associated with increased ICC risk included biliary tract diseases (adjusted odds ratio [AOR]: 81.8; 95% confidence interval [CI]: 11.2-598.8; P < 0.001), cirrhosis (AOR, 8.0; 95% CI: 1.8-36.5; P = 0.007), diabetes (AOR, 3.6; 95% CI: 2.3-5.5; P < 0.001), and smoking (AOR, 1.6; 95% CI: 1.3-2.1; P < 0.001). Compared to diabetic patients not treated with metformin, the odds ratio (OR) for ICC for diabetic patients treated with metformin was significantly decreased (OR, 0.4; 95% CI: 0.2-0.9; P = 0.04). Obesity and metabolic syndrome were not associated with ICC. Conclusion: This study confirmed diabetes and smoking as independent risk factors for ICC. A novel finding was that treatment with metformin was significantly associated with a 60% reduction in ICC risk in diabetic patients. (HEPATOLOGY 2013)