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Familial Risk of Biliary Tract Cancers among Offspring and Its Interaction with Gallstones: A Population-Based Cohort
Hyun Jung Kim1,2, Tae Uk Kang3, Heather Swan1,2
1Cochrane Korea, Seoul, Korea.
Purpose:
This study aimed to estimate the familial risk of biliary tract cancer (BTC) encompassing bile duct cancer (BDC) and gallbladder cancer (GBC) in offspring and to evaluate the interaction between family history and gallstones.
Materials And Methods:
Korean National Health Insurance claims and Health Screening databases (2002-2018) were linked to create a cohort of 6,217,057 offspring and 3,655,642 parent couples from 1.4 million families. Incidence rate ratios (IRRs) and hazard ratios (HRs) compared BTC risk in offspring with versus without an affected parent. Interaction between family history and gallstones was assessed with the relative excess risk due to interaction (RERI). Subgroup analyses were stratified by age, sex, and residence in Clonorchis sinensis-endemic areas.
Results:
Offspring with an affected parent had a 2.17-fold higher BTC risk than those without (0.35 vs. 0.08 cases per 10,000 person-years). Maternal history conferred greater risk than paternal history (HR 3.20 vs. 1.33). The IRR was higher in younger offspring. GBC or BDC risk in offspring was significantly associated with maternal, but not paternal, history of the other biliary cancer type, whereas no same-site associations were detected. Familial risk was lower in endemic than in non-endemic regions. Offspring with both gallstones and a family history showed markedly elevated risk (HR 17.36; 95% CI 9.80-30.81), although the interaction was not statistically significant (RERI 7.63; 95% CI -2.32-17.58).
Conclusion:
Offspring with gallstones and a family history of BTC have more than a ten-fold increase in BTC risk. Early and intensive surveillance should be considered for this high-risk population.
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