Family History of Primary Liver Cancer Associated with Increased Risk for Extrahepatic CCA

June 2022, Vol 13, No 3

The subtypes of cholangiocarcinoma (CCA), including intrahepatic CCA and extrahepatic CCA, have various underlying tumor microenvironments, pathobiology, epidemiologic features, and risk factors; however, the genetic underpinnings of the CCA subtypes have not been previously defined.

Madhulika Eluri, MD, University of Texas MD Anderson Hematology/Oncology Fellowship, Houston, and colleagues conducted a case-control study to determine the correlation between a family history of primary liver cancer and the incidence of CCA in the United States. Dr Eluri presented the results of the study at the 2022 ASCO GI Cancers Symposium.

This study was conducted at MD Anderson Cancer Center and included 429 patients with pathologically confirmed CCA and 1075 healthy controls. Of the 429 patients with CCA, 308 patients had intrahepatic CCA and 121 had extrahepatic CCA.

Patients were interviewed regarding their family history of cancer, including the number of relatives with cancer, the type of cancer, the patient’s relationship with the relative, and the age at which the relative was diagnosed with cancer.

Besides hepatitis B virus infection and hepatitis C virus infection, having a family history of cancer was significantly associated with intrahepatic CCA (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.2) and extrahepatic CCA (OR, 1.6; 95% CI, 1.1-2.5). The prevalence of family history of primary liver cancer in first-degree members was higher in patients with extrahepatic CCA compared with patients with intrahepatic CCA (6.6% vs 1.6%, respectively). A higher proportion of patients in the extrahepatic CCA cohort had multiple relatives with primary liver cancer compared with the patients in the intrahepatic CCA cohort (4.1% vs 1%, respectively).

Although primary liver cancer in first-degree relatives was significantly associated with extrahepatic CCA (OR, 9.4; 95% CI, 2.9-30.7), no significant association was observed for patients with intrahepatic CCA (OR, 1.7; 95% CI, 0.5-5.9). All estimated ORs were adjusted for age, sex, race, smoking, alcohol, hepatitis virus infection, diabetes, and obesity.

The results of this case-control study indicate that having a family history of primary liver cancer in a first-degree family member is associated with an increased risk for extrahepatic CCA in the United States.

Source: Eluri M, Hatia R, Javle MM, Hassan M. The association of family history of primary liver cancer with cholangiocarcinoma: USA case-control study. Presented at: 2022 ASCO GI Cancers Symposium; January 20-22, 2022. Abstract 403.

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