Genetic predisposition in gastric cancer

Abstract

Introduction. Gastric cancer is a neoplasm with a starting point in the gastric mucosa, representing one of the most common malignant visceral locations. Although a decreasing incidence globally, gastric cancer remains one of the most common causes of cancer death. Diagnosed in the early stage, it is curable, but unfortunately, most cases are identified late, in advanced stages. Aim of the study. Elucidation of predisposing factors and molecular mechanisms underlying gastric cancer development. Materials and methods. Exploring bibliographic sources using databases: PubMed, Google Scholar Results. Gastric cancer presents a multifactorial pathology caused by the interaction between environmental factors - Helicobacter Pylori, major cancer agent - and the genetic factors of the host organism. Genetic predisposition plays a major role in gastric carcinogenesis, as there are classes of genes involved in mucosal protection, immune response to H. pylori infection, carcinogen detoxification, antioxidant protection, DNA damage repair and ability to cell proliferation. The protective genes of the gastric mucosa are the mucin genes. The subtypes MUC1 (G allele at rs4072037), MUC2, MUC5AC, MUC6 and the genes of the trefoil peptidepS2 peptide, factor 1 (TFF1), spasmolytic polypeptide (SP) and intestinal ITF factor). Detoxification genes: cytochrome P450 (CYP450) linked to metabolism I-CYP1A1 (Ile462Val), CYP2E1 and CYP2C19. Glutathione S-transferases (GSTs) in Phase II play a role in protecting cells against the onslaught of chemical carcinogens. The pro and antiinflammatory genes IL1B, TNF, LTA, IL 6, IL1RN, IL 10 and TGF B, play a key role in the development of CG.DNA-repair genes include methylenetetrahydrofolate reductase (MTHFR-C677T mutation, XRCC1 gene (Arg194Trp), HOGG1 with TT genotype, xeroderma pigmentosum (XPF) (rs744154) increase susceptibility. Tumor suppressor genes: p53 (Arg / Arg), p53CD72 associated with genetic susceptibility to gastric cancer is an important biomarker. H. pylori infection and p53 mutation have been shown to have a synergistic effect. NM23 is the first confirmed suppressor gene for tumor metastases. Conclusions. The study is based on the analysis of genetic variants that confer a higher risk of CG and their interactions with environmental factors, respectively H. pylori infection. Candidate gene polymorphisms in gastric cancer susceptibility. A deeper understanding of the factors involved in the development and progression of CG may allow the identification of persons at risk and can provide useful predictive information for the subgroups of patients who need early treatment or surveillance strategies.