Highlights
- •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 < 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.
Keywords
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Article info
Publication history
Published online: August 17, 2017
Accepted:
August 6,
2017
Received in revised form:
August 4,
2017
Received:
May 17,
2017
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
