Risk Factors for Intrahepatic Cholangiocarcinoma:... : Hepatology (original) (raw)

Hepatobiliary Malignancies

Risk Factors for Intrahepatic Cholangiocarcinoma: Association Between Metformin Use and Reduced Cancer Risk

Chaiteerakij, Roongruedee1,2; Yang, Ju Dong1; Harmsen, William S.3; Slettedahl, Seth W.3; Mettler, Teresa A.1; Fredericksen, Zachary S.4; Kim, Ray W.1; Gores, Gregory J.1; Roberts, Rosebud O.5; Olson, Janet E.5; Therneau, Terry M.3; Roberts, Lewis R.1

1_Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic and Mayo Clinic Cancer Center, Rochester, MN_

2_Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand_

3_Department of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine and Mayo Clinic Cancer Center, Rochester, MN_

4_Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN_

5_Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN_

Address reprint requests to: Lewis R. Roberts, M.B. Ch.B., Ph.D., Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 fax: 507-284-0762

E-mail:[email protected]

Received 17 June 2012; Accepted 24 September 2012

Potential conflict of interest: Nothing to report.

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.).

fax: 507-284-0762

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.