학술논문
Loss-of-function variants in ATM confer risk of gastric cancer.
Document Type
Article
Author
Helgason, Hannes; Gudbjartsson, Daniel F; Rafnar, Thorunn; Sigurdsson, Asgeir; Stacey, Simon N; Jonasdottir, Adalbjorg; le Roux, Louise; Gudmundsson, Julius; Johannsdottir, Hrefna; Oddsson, Asmundur; Gylfason, Arnaldur; Magnusson, Olafur T; Masson, Gisli; Sulem, Patrick; Olafsdottir, Halla S; Alexiusdottir, Kristin; Jonasson, Jon G; Tryggvadottir, Laufey; Haraldsson, Asgeir; Jonsson, Thorvaldur
Source
Subject
*PATHOGENIC microorganisms
*PROSTATE cancer & genetics
*GENOMES
*DNA mutational analysis
*CARCINOMA
*TUMORS
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Language
ISSN
1061-4036
Abstract
Gastric cancer is a serious health problem worldwide, with particularly high prevalence in eastern Asia. Genome-wide association studies (GWAS) in Asian populations have identified several loci that associate with gastric cancer risk. Here we report a GWAS of gastric cancer in a European population, using information on 2,500 population-based gastric cancer cases and 205,652 controls. We found a new gastric cancer association with loss-of-function mutations in ATM (gene test, P = 8.0 × 10−12; odds ratio (OR) = 4.74). The combination of the loss-of-function variants p.Gln852*, p.Ser644* and p.Tyr103* (combined minor allele frequency (MAF) = 0.3%) also associates with pancreatic and prostate cancers (OR = 3.81 and 2.18, respectively) and gives an indication of risk of breast and colorectal cancers (OR = 1.82 and 1.97, respectively). Cancers in those carrying loss-of-function ATM mutations are diagnosed at a significantly earlier age than in non-carriers. Our results confirm an association between gastric cancer in Europeans and three loci previously reported in Asians, MUC1, PRKAA1 and PSCA, refine the association signal at PRKAA1 and support a pathogenic role for the tandem repeat identified in MUC1. [ABSTRACT FROM AUTHOR]