Abstract
The identification of hereditary cancer genes for esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE), may prove critical for the development of novel prevention and treatment strategies. Specifically, efforts for detecting BE and EAC susceptibility genes have focused on families with three or more affected members, since these individuals have an earlier age onset compared to non-familial individuals. Given that the use of BE may overestimate the likelihood of disease heritability, we evaluated the age of diagnosis in kindreds with a restricted definition including only confirmed high-grade dysplasia (HGD) or EAC. The Familial Barrett’s Esophagus Consortium database was used to identify individuals with HGD and EAC. These individuals were subsequently split into three kindred groups: non-familial—a single affected family member, duplex—two affected family members, and multiplex—three or more affected family members. Age of cancer diagnosis and other risk factors were compared between individuals in these groups. The study included 441 non-familial, 46 duplex, and 13 multiplex individuals. There was a statistically significant difference for age of diagnosis for individuals in the multiplex families compared to the non-familial and duplex families (56.0 versus 64.3, 63.5; p = 0.049). There was no significant difference between demographic factors and other cancer risk factors between family types. The results of this study support a genetic basis for familial Barrett’s associated neoplasia and evaluation of the genetic susceptibility to this disease should continue to focus on families with multiple (three or more) affected members.
References
Coleman HG, Xie SH, Lagergren J (2018) The epidemiology of esophageal adenocarcinoma. Gastroenterology 154:390–405
Rahman N (2014) Realizing the promise of cancer predisposition genes. Nature 505:302–308
Spechler SJ, Souza RF (2014) Barrett’s esophagus. N Engl J Med 371:836–845
Chak A, Ochs-Balcom H, Falk G et al (2006) Familiality in Barrett’s esophagus, adenocarcinoma of the esophagus, and adenocarcinoma of the gastroesophageal junction. Cancer Epidemiol Biomark Prev 15:1668–1673
Drovdlic CM, Goddard KA, Chak A et al (2003) Demographic and phenotypic features of 70 families segregating Barrett’s oesophagus and oesophageal adenocarcinoma. J Med Genet 40:651–656
Sun X, Elston R, Barnholtz-Sloan J et al (2010) A segregation analysis of Barrett’s esophagus and associated adenocarcinomas. Cancer Epidemiol Biomark Prev 19:666–674
Verbeek RE, Spittuler LF, Peute A et al. Familial clustering of Barrett’s esophagus and esophageal adenocarcinoma in a European cohort. Clin Gastroenterol Hepatol 2014;12:1656–1663 e1
Chak A, Falk G, Grady WM et al (2009) Assessment of familiality, obesity, and other risk factors for early age of cancer diagnosis in adenocarcinomas of the esophagus and gastroesophageal junction. Am J Gastroenterol 104:1913–1921
Chak A, Chen Y, Vengoechea J et al (2012) Variation in age at cancer diagnosis in familial versus nonfamilial Barrett’s esophagus. Cancer Epidemiol Biomark Prev 21:376–383
Fecteau RE, Kong J, Kresak A et al (2016) Association between germline mutation in VSIG10L and familial Barrett neoplasia. JAMA Oncol 2:1333–1339
Funding
This research was supported by U54CA163060, P50CA150964, P30DK09794, T35DK111373 (BKG), IK2CX001831 (AEB).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
WMG is on the advisory boards for Freenome, Guardant Health, and SEngine and consults for Diacarta. He is also an investigator for a clinical trial sponsored by Janssen and receives services for investigator initiated research from Tempus and Lucid Technologies. AC is a shareholder, consultants to and has a royalty interest in technology licensed to Lucid Diagnostics. AC has also consulted for Interpace Diagnostics.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Glamour, B.K., Alaber, O., Cioffi, G. et al. Age of diagnosis in familial Barrett’s associated neoplasia. Familial Cancer 21, 115–120 (2022). https://doi.org/10.1007/s10689-021-00239-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-021-00239-z