Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: A population-based study in SEER-Medicare

Abstract

ObjectivesIntrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinomas are rare tumors that arise from the epithelial cells of the bile ducts, and the etiology of both cancer types is poorly understood. Thus, we utilized the Surveillance, Epidemiology, and End Results (SEER)-Medicare resource to examine risk factors and novel preexisting medical conditions that may be associated with these cancer types.MethodsBetween 2000 and 2011, 2,092 ICC and 2,981 ECC cases and 323,615 controls were identified using the SEER-Medicare database. Logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsNon-alcoholic fatty liver disease was associated with approximately 3-fold increased risks of ICC (OR = 3.52, 95% CI: 2.87–4.32) and ECC (OR = 2.93, 95% CI: 2.42–3.55). Other metabolic conditions, including obesity and type 2 diabetes, were also associated with increased risks of both cancer types. Smoking was associated with a 46% and 77% increased ICC and ECC risk, respectively. Several autoimmune/inflammatory conditions, including type 1 diabetes and gout, were associated with increased risks of ICC/ECC. As anticipated, viral hepatitis, alcohol-related disorders, and bile duct conditions were associated with both cancer types. However, thyrotoxicosis and hemochromatosis were associated with an increased risk of ICC but not ECC, but did not remain significantly associated after Bonferroni correction.ConclusionsIn this study, risk factors for ICC and ECC were similar, with the exceptions of thyrotoxicosis and hemochromatosis. Notably, metabolic conditions were associated with both cancer types. As metabolic conditions are increasing in prevalence, these could be increasingly important risk factors for both types of cholangiocarcinoma.

Biliary tract cancer incidence and trends in the United States by demographic group, 1999‐2013

“…As in previous studies, we found higher ICC incidence rates for males, Hispanics and other non‐Hispanic racial/ethnic groups, and older ages. ICC risk factors include chronic liver diseases and cirrhosis, biliary stones, infections (hepatitis B and C viruses and liver flukes), bile duct anomalies, some autoimmune diseases, obesity, diabetes, and smoking . Although the prevalence of these risk factors differs by demographic group, the commonality is that they involve inflammatory processes.…”

Cholangiocarcinoma: Epidemiology and risk factors

“…Some case reports and case series suggest an association between hemochromatosis and iCCA development . Results from the US SEER registry reported an OR = 2.07 (95% CI 1.33‐3.22) for iCCA, whereas no increased risk was found for eCCA . This last finding is not totally surprising, as iron deposition preferentially occurs in the liver.…”

“…Both ulcerative colitis and Crohn's disease were found to be associated with increased CCA risk, although a stronger association was found for ulcerative colitis (RR = 3.40, 95% CI 2.50‐4.62 vs RR = 2.69, 95% CI 1.59‐4.55 respectively) . A recent analysis based on the US SEER registry also confirmed a stronger association with iCCA for ulcerative colitis (OR = 2.18, 95% CI 1.61‐2.95) compared to Crohn's disease (OR = 1.77, 95% CI 1.13‐2.75), whereas a similar increased risk was found for eCCA (OR = 1.75, 95% CI 1.32‐2.33 vs OR = 1.71, 95% CI 1.17‐2.51) . Both pathological conditions may be related to CCA development by induction of chronic inflammation and/or microbiome dysbiosis .…”

Postbiliary drainage rates of cholangitis are impacted by procedural technique for patients with supra‐ampullary cholangiocarcinoma: A SEER‐Medicare analysis

“…This study utilized deidentified SEER‐Medicare data and therefore has been determined to meet criteria for exemption from IRB requirements by the NIH Office of Human Subjects Research Protections. The SEER database catalogs information on cancer cases reported in 18 regional registries across the United States, representing approximately 28% of the American population . Prospective data collection includes patient demographics and cancer‐specific information, including tumor histology, stage at diagnosis, treatment, and clinical outcomes.…”