Genetics & epigenetics of gastric cancer

Gastric cancer(GC) is the fifth most common malignancy worldwide, and accounts for a notable proportion of cancer. GC is a complex disease influenced by both genetic and epigenetic factors. An inherited component contributes to <۳% of GC; the majority of genetic changes associated with GC are acquired. GC is a solid tumour with complex genetic and environmental interactions that contribute to its initiation and progression Most GC are adenocarcinomas. Traditionally, GC is divided into two main subtypes on the basis of Lauren’s classification—intestinal and diffuse.These subtypes have different molecular profiles, and their develop ment pathways are distinct.Understanding the genetic basis of GC will offer insights into its pathogenesis, help identify new biomarkers and novel treatment targets, aid prognostication and could be central to developing individualized treatment strategies in the future. As a key risk factor of gastric cancer, H. pylori infection is an independent predictive indicator of gene methylation. A growing number of epigenetic studies in GC have provided lots of potential diagnostic and prognostic markers and therapeutic targets. Materials and Methods: A systematic literature review was conducted using PubMed, Web of Science, and Scopus databases. Keywords related to gastric cancer, genetics, and epigenetics were utilized to identify relevant studies published up to the latest search date. The search strategy focused on English-language articles, including original research, reviews, and meta-analyses. Data extraction and synthesis were performed to analyze the genetic mutations and epigenetic alterations reported in GC. Results:Genes involved in cancer-related pathways were more frequently affected by epigenetic alterations than by genetic alterations.GC remains a global killer with a very poor prognosis. The causative agent of this cancer, H. pylori infection, is one of the world’s most common chronic bacterial infections.The study of the genetic basis of gastric cancer, including host genetic susceptibility, has shed considerable light on the pathogenesis of this disease and has highlighted the role of infection and chronic inflammation in GC. Discussion:GC remains a significant contributor to cancer-related mortality. Risk factors for the condition include Helicobacter pylori infection, age, high salt intake, and diets low in fruit and vegetables. The most frequent hereditary gastric cancer syndrome is hereditary diffuse gastric cancer (HDGC).This autosomal dominant condition is associated most frequently with a heterozygous germline mutation in CDH۱, the gene that encodes cadherin ۱. include the untranslated regions. A loss-of function mutation in the remaining allele can be caused by a number of mechanisms, such as loss of heterozygosity or promoter hypermethylation, and can lead to GC. .Epigenetic changes frequently occur in human GC. Gene promoter region hypermethylation, genomic global hypomethylation, histone modifications, and alterations of noncoding RNAs are major epigenetic changes in GC Novel high throughput techniques have enlightened the epigenetic mechanisms governing gene-expression regulation.Epigenetic characteristics contribute to molecular taxonomy and give rise to cancer-specific epigenetic patterns.Helicobacter pylori (Hp) infection has an impact on aberrant DNA methylation either through its pathogenic CagA protein or by inducing chronic inflammation.

کلیدواژه ها:

Gastric cancer ، Genetic ، Epigenetic ، H. Pylori ، HDGC syndrome