Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.

Original publication

DOI

10.1053/j.gastro.2016.12.010

Type

Journal article

Journal

Gastroenterology

Publication Date

04/2017

Volume

152

Pages

983 - 986.e6

Addresses

Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California.

Keywords

Latin American Gastric Cancer Genetics Collaborative Group, Humans, Stomach Neoplasms, Genetic Predisposition to Disease, DNA-Binding Proteins, Tumor Suppressor Proteins, BRCA1 Protein, Nuclear Proteins, Mutation, Germ-Line Mutation, Aged, Aged, 80 and over, Middle Aged, Female, Male, Recombinational DNA Repair, Fanconi Anemia Complementation Group N Protein