Genetic Gastric Cancer Susceptibility in the International Clinical Cancer Genomics Community Research Network.

Abstract

Few susceptibility genes for gastric cancer have been identified. We sought to identify germline susceptibility genes from participants with gastric cancer from an international hereditary cancer research network. Adults with gastric cancer of any histology, and with a germline DNA sample (n = 51), were retrospectively selected. For those without previously identified germline mutations (n = 43), sequencing was performed for 706 candidate genes. Twenty pathogenic or likely pathogenic variants were identified among 18 participants. Eight of the 18 participants had previous positive clinical testing, including six with CDH1 pathogenic or likely pathogenic variants, and two with pathogenic MSH2 and TP53 variants. Of the remaining 10, six were in BRCA1 DNA damage response pathway genes (ATM, ATR, BRCA2, BRIP1, FANCC, TP53), other variants were identified in CTNNA1, FLCN, SBDS, and GNAS. Participants identified with pathogenic or likely pathogenic variants were younger at gastric cancer diagnosis than those without, 39.1 versus 48.0 years, and over 50% had a close family member with gastric cancer (p-values < 0.0001). In conclusion, many participants were identified with mutations in clinically-actionable genes. Age of onset and family history of gastric cancer were mutation status predictors. Our findings support multigene panels in identifying gastric cancer predisposition.

• Authors: Thomas Slavin, Susan L Neuhausen, Christina Rybak, Ilana Solomon, Bita Nehoray, Kathleen Blazer, Mariana Niell-Swiller, Aaron W Adamson, Yate-Ching Yuan, Kai Yang, Sharon Sand, Danielle Castillo, Josef Herzog, Xiwei Wu, Shu Tao, Tanya Chavez, Yanghee Woo, Joseph Chao, Pamela Mora, Darling Horcasitas, Jeffrey Weitzel
• Journal: Cancer genetics (Cancer Genet) Vol. 216-217 Pg. 111-119 (Oct 2017) ISSN: 2210-7762 [Print] United States
• PMID: 29025585 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomedical Research
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genetic Testing
• Genomics
• Germ-Line Mutation (genetics)
• Humans
• Internationality
• Male
• Middle Aged
• Sequence Analysis, DNA
• Signal Transduction (genetics)
• Stomach Neoplasms (genetics)
• Young Adult