Association between Polymorphisms in Inflammatory Response-Related Genes and the Susceptibility, Progression and Prognosis of the Diffuse Histological Subtype of Gastric Cancer

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorFURUYA, Tatiane K.
dc.contributor.authorJACOB, Carlos E.
dc.contributor.authorTOMITAO, Michele T. P.
dc.contributor.authorCAMACHO, Lizeth C. C.
dc.contributor.authorRAMOS, Marcus F. K. P.
dc.contributor.authorELUF-NETO, Jose
dc.contributor.authorALVES, Venancio A. F.
dc.contributor.authorZILBERSTEIN, Bruno
dc.contributor.authorCECCONELLO, Ivan
dc.contributor.authorRIBEIRO JR., Ulysses
dc.contributor.authorCHAMMAS, Roger
dc.date.accessioned2019-02-21T17:27:10Z
dc.date.available2019-02-21T17:27:10Z
dc.date.issued2018
dc.description.abstractThe chronic inflammatory microenvironment and immune cell dysfunction have been described as critical components for gastric tumor initiation and progression. The diffuse subtype is related to poor clinical outcomes, pronounced inflammation, and the worst prognosis. We investigated the association of polymorphisms in inflammatory response-related genes (COX-2, OGG1, TNFB, TNFA, HSPA1L, HSPA1B, VEGFA, IL17F, LGALS3, PHB, and TP53) with gastric cancer susceptibility, progression and prognosis in a Brazilian sample, focusing on the diffuse subtype. We also performed the analysis regarding the total sample of cases (not stratified for tumor subtypes), allowing the comparison between the findings. We further investigated the polymorphisms in linkage disequilibrium and performed haplotype association analyses. In the case-control study, rs1042522 (TP53) was associated with a stronger risk for developing gastric cancer in the sample stratified for diffuse subtype patients when compared to the risk observed for the total cases; CTC haplotype (rs699947 / rs833061 / rs2010963 VEGFA) was associated with risk while rs699947 was associated with protection for gastric malignancy in the total sample. Regarding the associations with the clinicopathological features of gastric cancer, for the diffuse subtype we found that rs699947 and rs833061 (VEGFA) were associated with outcomes related to a worse progression while rs5275 (COX-2), rs909253 (TNFB), and rs2227956 (HSPA1L) were associated to a better progression of the disease. In the total sample, rs699947 and rs833061 (VEGFA), rs4644 (LGALS3), and rs1042522 (TP53) were able to predict a worse progression while rs5275 (COX-2), rs2227956 (HSPA1L), and rs3025039 (VEGFA) a better progression. Besides, rs909253 (TNFB) predicted protection for the overall and disease-free survivals for gastric cancer. In conclusion, these results helped us to clarify the potential role of these polymorphisms in genes involved in the modulation of the inflammatory response in the pathogenesis of gastric cancer.eng
dc.description.indexPubMedeng
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil)
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil)
dc.identifier.citationGENES, v.9, n.12, article ID 631, 22p, 2018
dc.identifier.doi10.3390/genes9120631
dc.identifier.issn2073-4425
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/30889
dc.language.isoeng
dc.publisherMDPIeng
dc.relation.ispartofGenes
dc.rightsopenAccesseng
dc.rights.holderCopyright MDPIeng
dc.subjectgastric cancereng
dc.subjectdiffuse histological subtype of Laureneng
dc.subjectgenetic polymorphismseng
dc.subjecthaplotypeseng
dc.subjectinflammationeng
dc.subjectgenetic association studieseng
dc.subjectgenetic predisposition to diseaseeng
dc.subjectdisease progressioneng
dc.subjectprognosiseng
dc.subject.otherendothelial growth-factoreng
dc.subject.otherbreast-cancereng
dc.subject.otherarg72pro polymorphismeng
dc.subject.othermutationeng
dc.subject.otherriskeng
dc.subject.otherexpressioneng
dc.subject.othervariantseng
dc.subject.othercyclooxygenase-2eng
dc.subject.otherpopulationeng
dc.subject.otherlocuseng
dc.subject.wosGenetics & Heredityeng
dc.titleAssociation between Polymorphisms in Inflammatory Response-Related Genes and the Susceptibility, Progression and Prognosis of the Diffuse Histological Subtype of Gastric Cancereng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.citation.scopus19
hcfmusp.contributor.author-fmusphcTATIANE KATSUE FURUYA
hcfmusp.contributor.author-fmusphcCARLOS EDUARDO JACOB
hcfmusp.contributor.author-fmusphcMICHELE TATIANA PEREIRA TOMITAO
hcfmusp.contributor.author-fmusphcLIZETH CAROLINA CORDOBA CAMACHO
hcfmusp.contributor.author-fmusphcMARCUS FERNANDO KODAMA PERTILLE RAMOS
hcfmusp.contributor.author-fmusphcJOSE ELUF NETO
hcfmusp.contributor.author-fmusphcVENANCIO AVANCINI FERREIRA ALVES
hcfmusp.contributor.author-fmusphcBRUNO ZILBERSTEIN
hcfmusp.contributor.author-fmusphcIVAN CECCONELLO
hcfmusp.contributor.author-fmusphcULYSSES RIBEIRO JUNIOR
hcfmusp.contributor.author-fmusphcROGER CHAMMAS
hcfmusp.description.articlenumber631
hcfmusp.description.issue12
hcfmusp.description.volume9
hcfmusp.origemWOS
hcfmusp.origem.pubmed30551681
hcfmusp.origem.scopus2-s2.0-85060615143
hcfmusp.origem.wosWOS:000454717800065
hcfmusp.publisher.cityBASELeng
hcfmusp.publisher.countrySWITZERLANDeng
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