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

•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. Few susceptibility genes for gastric cancer have be...

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Published in:Cancer genetics 2017-10, Vol.216-217, p.111-119
Main Authors: Slavin, Thomas, Neuhausen, Susan L., Rybak, Christina, Solomon, Ilana, Nehoray, Bita, Blazer, Kathleen, Niell-Swiller, Mariana, Adamson, Aaron W., Yuan, Yate-Ching, Yang, Kai, Sand, Sharon, Castillo, Danielle, Herzog, Josef, Wu, Xiwei, Tao, Shu, Chavez, Tanya, Woo, Yanghee, Chao, Joseph, Mora, Pamela, Horcasitas, Darling, Weitzel, Jeffrey
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Biomedical Research
family
Female
gastric cancer
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Testing
genetics
Genomics
Germ-Line Mutation - genetics
Humans
Internationality
Male
Middle Aged
Sequence Analysis, DNA
Signal Transduction - genetics
Stomach Neoplasms
Stomach Neoplasms - genetics
Young Adult
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Summary:•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. 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 
ISSN:2210-7762
2210-7770
DOI:10.1016/j.cancergen.2017.08.001