The association of family history of primary liver cancer with cholangiocarcinoma: USA case-control study.

Abstract

403 Background: The incidence of cholangiocarcinoma (CCA), particularly intrahepatic cholangiocarcinoma (IHC) has exponentially increased in the United States since 2007. While cholangiocarcinomas share some common characteristics, increasing evidence suggests that different subtypes of CCA have divergent tumor microenvironments, pathobiology and distinct epidemiologic features and risk factors. The correlation between family history of cancer and cholangiocarcinoma remains to be determined. This study aims to address the connection between positive family history of primary liver cancer and development of cholangiocarcinoma, including intrahepatic cholangiocarcinoma (IHC) and extrahepatic cholangiocarcinoma (EHC), in USA. Methods: At The University of Texas M. D. Anderson Cancer Center, we studied 429 patients with pathologically confirmed cholangiocarcinoma (308 IHC, 121 EHC) and 1,075 healthy controls. All subjects were interviewed for their family history of cancer, including the number of relatives with cancer, the type of cancer, the subjects’ relationship with the relative, and the age at which the relative was diagnosed. Results: Independent of hepatitis B virus (HBV) and hepatitis C virus (HCV), a family history of cancer was significantly associated with IHC and EHC, the estimated ORs and 95% CI were 1.6 (1.2-2.2) and 1.6 (1.1-2.5) for IHC and EHC respectively. Primary liver cancer in first-degree relatives was significantly associated with EHC development (OR 9.4 [95% CI, 2.9-30.7]). No significant association was observed for IHC, (OR 1.7 [95% CI, 0.5-5.9]). The prevalence of family history of primary liver cancer in first-degree members was recorded in 6.6% of EHC patients and in 1.6% of IHC patients. Multiple relatives with primary liver cancer were observed in 5 patients (4.1%) among EHC subjects but less common in IHC (1%). All estimated ORs were adjusted for age, sex, race, smoking, alcohol, Hepatitis virus infection, diabetes, and obesity. Conclusions: First-degree family history of primary liver cancer is associated with EHC development in USA independent of known risk factors for CCA. Further research exploring the genetic–environment interactions associated with EHC is warranted. Focused efforts in identifying the population at increased risk for developing EHC are necessary and may lead to new screening and surveillance strategies.