| Literature DB >> 26098866 |
Hannes Helgason1, Thorunn Rafnar2, Halla S Olafsdottir3, Jon G Jonasson4, Asgeir Sigurdsson2, Simon N Stacey2, Adalbjorg Jonasdottir2, Laufey Tryggvadottir5, Kristin Alexiusdottir3, Asgeir Haraldsson6, Louise le Roux2, Julius Gudmundsson2, Hrefna Johannsdottir2, Asmundur Oddsson2, Arnaldur Gylfason2, Olafur T Magnusson2, Gisli Masson2, Thorvaldur Jonsson7, Halla Skuladottir8, Daniel F Gudbjartsson1, Unnur Thorsteinsdottir9, Patrick Sulem2, Kari Stefansson9.
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.Entities:
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Year: 2015 PMID： 26098866 DOI： 10.1038/ng.3342
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330