Risk Factors for Intrahepatic and Extrahepatic Cholangiocarcinoma in the United States: A Population-Based Case-Control Study

• Published in: Clinical gastroenterology and hepatology Vol. 5; no. 10; pp. 1221 - 1228
• Main Authors: Welzel, Tania M, Graubard, Barry I, El–Serag, Hashem B, Shaib, Yasser H, Hsing, Ann W, Davila, Jessica A, McGlynn, Katherine A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2007
• Subjects: Aged; Bile Duct Neoplasms - epidemiology; Bile Ducts, Extrahepatic; Bile Ducts, Intrahepatic; Cholangiocarcinoma - epidemiology; Female; Gastroenterology and Hepatology; Humans; Incidence; Male; Population Surveillance; Retrospective Studies; Risk Factors; SEER Program - statistics & numerical data; Survival Rate; United States - epidemiology; United States; health maintenance organization; PSC; NAFLD; ECC; ICC; HCC; Surveillance Epidemiology and End Results program; HMO; intrahepatic cholangiocarcinoma; PBC; nonalcoholic fatty liver disease; ICD-9-CM; primary biliary cirrhosis; Current Procedural Terminology, version 4; SEER; International Classification of Diseases-ninth revision-Clinical Modification; CPT-4; extrahepatic cholangiocarcinoma; hepatocellular carcinoma; primary sclerosing cholangitis
• ISSN: 1542-3565; 1542-7714
• DOI: 10.1016/j.cgh.2007.05.020

Background & Aims: Intrahepatic and extrahepatic cholangiocarcinomas are rare and highly malignant cancers of the bile duct. Although the incidence of extrahepatic cholangiocarcinoma (ECC) has remained constant, the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the United States. Because the etiology of both tumors is poorly understood, a population-based case-control study was conducted to examine the association of ECC and ICC with preexisting medical conditions. Methods: Medical conditions among 535 ICC patients, 549 ECC patients (diagnosed 1993–1999), and 102,782 cancer-free controls were identified by using the Surveillance, Epidemiology and End Results–Medicare databases. Logistic regression analysis was used to calculate adjusted odds ratios. Results: In addition to established risk factors (choledochal cysts, cholangitis, inflammatory bowel disease), several other conditions were significantly associated with ECC and ICC: biliary cirrhosis (ECC, ICC: P < .001), cholelithiasis (ECC, ICC: P < .001), alcoholic liver disease (ECC, P < .001; ICC, P = .01), nonspecific cirrhosis (ECC, ICC: P < .001), diabetes (ECC, ICC: P < .001), thyrotoxicosis (ECC, P = .006; ICC, P = .04), and chronic pancreatitis (ECC, ICC: P < .001). Conditions only associated with ICC were obesity (ECC, P = .71; ICC, P = .01), chronic nonalcoholic liver disease (ECC, P = .08; ICC, P = .02), HCV infection (ECC, P = .67; ICC, P = .01), and smoking (ECC, P = .07; ICC, P = .04). Conclusions: Several novel associations with ECC and ICC were identified. HCV infection, chronic nonalcoholic liver disease, and obesity, all of which are increasing in incidence, and smoking were associated only with ICC, suggesting that these conditions might explain the divergent incidence trends of the tumors.