Risk factors for intrahepatic cholangiocarcinoma: association between metformin use and reduced cancer risk.
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.


CONCLUSIONS
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.
Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic and Mayo Clinic Cancer Center, Rochester, MN 55905, USA.
Roongruedee
R
Chaiteerakij
Ju Dong
JD
Yang
William S
WS
Harmsen
Seth W
SW
Slettedahl
Teresa A
TA
Mettler
Zachary S
ZS
Fredericksen
W Ray
WR
Kim
Gregory J
GJ
Gores
Rosebud O
RO
Roberts
Janet E
JE
Olson
Terry M
TM
Therneau
Lewis R
LR
Roberts
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000209:etiology; D001653:Bile Ducts, Intrahepatic; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000209:etiology* / Q000517:prevention & control; D048909:Diabetes Complications / Q000517:prevention & control; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000188:drug therapy; D008113:Liver Neoplasms / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008687:Metformin