Abstract
Background and Objectives
Biliary tract cancers (BTC) including, cholangiocarcinoma (CC) and gallbladder cancer (GBC), are rare and highly fatal malignancies. The etiology and inherited susceptibility of both malignancies are poorly understood. We quantified the risk of BTC in first-degree (FDR), second-degree (SDR), and first cousin (FC) relatives of individuals with BTC, stratified by tumor subsite.
Methods
BTC diagnosed between 1980 and 2011 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age- and gender-matched BTC-free controls were selected to form the comparison group for determining BTC risk in relatives using Cox regression analysis.
Results
Of the 1302 index patients diagnosed with BTC, 550 (42.2 %) were located in the gallbladder and 752 (57.8 %) were cholangiocarcinomas. There was no elevated risk of BTC (all subsites combined) in FDRs (HR 0.94, 95 % CI 0.29–3.0), SDRs (HR 0.25, 95 % CI 0.06–1.03), and FCs (HR 0.96, 95 % CI 0.61–1.51) of BTC cases compared to cancer-free controls. Similarly, no increased familial risk of GBC or CC was found in relatives of BTC patients stratified by tumor subsite compared to relatives of controls.
Conclusions
Relatives of BTC patients are not at an increased risk of GBC or CC in a statewide population. This suggests that biliary tract cancer risk is not associated with a familial predisposition and may be mitigated more strongly by environmental modifiers.
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Acknowledgments
The study was funded by the National Cancer Institute, American College of Gastroenterology, American Society for Gastrointestinal Endoscopy, and the Huntsman Cancer Foundation. The funding sources did not play a role in the design, conduct or reporting of the study or in the decision to submit the manuscript for publication. Support for this project was provided by NCI Grants P01-CA073992 (RWB), R01-CA040641 (RWB), an Endoscopic Research Award from the American Society for Gastrointestinal Endoscopy (NJS), and a Junior Faculty Career Development Award from the American College of Gastroenterology (NJS). Partial support for the Utah Population Database and this project was provided by the Huntsman Cancer Institute Cancer Center Support Grant P30CA042014 from the National Cancer institute and the Huntsman Cancer Foundation. Support for the Utah Cancer Registry is provided by Contract #HHSN 261201000026C from the National Cancer Institute with additional support from the Utah Department of Health and the University of Utah.
Author contributions
Drs. Samadder and Curtin had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analyses. RWB, KC, and NJS contributed to study concept and design; acquisition, analysis, and interpretation of data were performed by HH, KS, KC, JW, KB, JG, MC, RWB, and NJS; KC and NJS drafted the manuscript; HH, KC, KS, JW, KB, KC, MC, JG, and RWB critically revised the manuscript for important intellectual content; statistical analysis was carried out by JW, KC, KB, and DZY; NJS and RWB obtained funding.
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RWB is a consultant for Myriad Genetics, and NJS is a consultant for Cook Medical. No other authors have a conflict of interest to disclose.
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Samadder, N.J., Smith, K.R., Wong, J. et al. Familial Risk of Biliary Tract Cancers: A Population-Based Study in Utah. Dig Dis Sci 61, 3627–3632 (2016). https://doi.org/10.1007/s10620-016-4310-3
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DOI: https://doi.org/10.1007/s10620-016-4310-3