Genetic Variations and Gastric Cancer

Abstract

Background: Gastric cancer (GC) has an apparent hereditary component. However, in a large fraction of gastric cases, no known genetic syndrome or family history can be identified, suggesting the presence of ‘missing heritability' in GC etiology. Genome-wide association studies (GWAS) and traditional candidate gene studies have both led to the identification of multiple replicable common genetic variants associated with GC risk. Summary: We summarize the genetic variants associated with GC risk identified up to date. Achievements derived from translational cancer research including the following aspects: (a) contribution to the our understanding of gastric tumorigenesis, (b) guidance to individualized treatment and (c) prediction of patient prognosis. We also prospect future research direction such as post-GWAS analyses and rare variants studies. Key Message: Many genetic variants were found through GWAS or candidate gene studies, and interpreting their underlying mechanisms will help us translate risk profiles generated from these variations into use in the clinical setting for targeted screening and treatment. Practical Implications: Investigation of the potential use of genetic variations as prognostic and predictive markers is a developing field. Many people could benefit from a better understanding of genetic polymorphisms to potentially identify a priori individuals who might have the best chance of survival and therefore derive most clinical benefit from treatment. Outcomes of particular scientific interest for molecular epidemiologic studies should include overall survival, recurrence- and progression-free survival, response to treatment, and early and late toxicities stemming from chemotherapy and radiation.

Genetic Disorder and Cancer

“…Co-segregation of germline E-cadherin (CDH1) mutations with early onset diffuse gastric cancer in families with an autosomal dominant pattern of inheritance (HDGC) show that gastric cancer is hereditary in nature. APC, a tumour-suppressor gene and is associated with colorectal cancer [23][24][25].…”