Genetic variant of cyclooxygenase-2 in gastric cancer:More inflammation and susceptibility

Gastric cancer accounts for the majority cancer-related deaths worldwide.Although various methods have considerably improved the screening,diagnosis,and treatment of gastric cancer,its incidence is still high in Asia,and the 5-year survival rate of advanced gastric cancer patients is only 10%-20%.Therefore,more effective drugs and better screening strategies are needed for reducing the incidence and mortality of gastric cancer.Cyclooxygenase-2(COX-2)is considered to be the key inducible enzyme in prostaglandins(PGs)synthesis,which is involved in multiple pathways in the inflammatory response.For example,inflammatory cytokines stimulate innate immune responses via Toll-like receptors and nuclear factor-kappa B to induce COX-2/PGE2 pathway.In these processes,the production of an inflammatory microenvironment promotes the occurrence of gastric cancer.Epidemiological studies have also indicated that non-steroidal antiinflammatory drugs can reduce the risk of malignant tumors of the digestive system by blocking the effect of COX-2.However,clinical use of COX-2 inhibitors to prevent or treat gastric cancer may be limited because of potential side effects,especially in the cardiovascular system.Given these side effects and low treatment efficacy,new therapeutic approaches and early screening strategies are urgently needed.Some studies have shown that genetic variation in COX-2 also play an important role in carcinogenesis.However,the genetic variation analysis in these studies is incomplete and isolated,pointing out only a few single nucleotide polymorphisms(SNPs)and the risk of gastric cancer,and no comprehensive study covering the whole gene region has been carried out.In addition,copy number variation(CNV)is not mentioned.In this review,we summarize the SNPs in the whole COX-2 gene sequence,including exons,introns,and both the 5’and 3’untranslated regions.Results suggest that COX-2 does not increase its expression through the CNV and the SNPs in COX-2 may serve as the potential marker to establish risk stratification in the general population.This review synthesizes emerging insights of COX-2 as a biomarker in multiple studies,summarizes the association between whole COX-2 sequence variation and susceptibility to gastric cancer,and discusses the future prospect of therapeutic intervention,which will be helpful for early screening and further research to find new approaches to gastric cancer treatment.

Helicobacter pylori and gastric cardia cancer:What do we know about their relationship?

The incidence of gastric cardia cancer is increasing around the world.Since the discovery of Helicobacter pylori(H.pylori),numerous studies have proved that it is a causative factor for many kinds of digestive system tumors.Although the literature on gastric cardia cancer and H.pylori is not scarce,there are still many controversies on the relationship between gastric cardia cancer and H.pylori.Many Western research results showed that there was a negative or no correlation between H.pylori infection and gastric cardia cancer,but in several studies in Asian countries,such as China,H.pylori was demonstrated to be a risk factor for gastric cardia cancer.Therefore,we intended to analyze the related studies to find out the relationship between H.pylori and gastric cardia cancer and find out the causes of the above controversies.We also conducted a metaanalysis of the relationship between cagA positive expression of H.pylori and gastric cardia cancer,to find out whether there is an effect between those two.The primary purpose of this paper was to explore the relationship between gastric cardia cancer and H.pylori.Through analysis,the study showed the reasons for the controversies mentioned above:(1)Geographical factors could affect the relationship between H.pylori and gastric cardia cancer;(2)The definition of gastric cardia cancer in various studies is inconsistent.The result of a meta-analysis about the relationship between H.pylori virulence factor cagA and gastric cardia cancer showed that there was no relationship between these two.