{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T12:15:02Z","timestamp":1771848902503,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sociedade Portuguesa de Gastrenterologia","award":["N\u00ba1\/2016"],"award-info":[{"award-number":["N\u00ba1\/2016"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BPD\/114803\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/114803\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The cyclooxygenase-2 (COX-2)\/prostaglandin E2 (PGE2) pathway exerts deleterious pleiotropic effects in inflammation-induced gastric carcinogenesis. We aimed to assess the association of genetic variants in prostaglandin-endoperoxide synthase 2 (PTGS2), ATP binding cassette subfamily C member 4 (ABCC4), hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), and solute carrier organic anion transporter family member 2A1 (SLCO2A1) PGE2 pathway-related genes with gastric cancer (GC) risk in a European Caucasian population. A hospital-based case-control study gathering 260 GC cases and 476 cancer-free controls was implemented. Using a tagSNP approach, 51 single nucleotide polymorphisms (SNPs) were genotyped through MassARRAY\u00ae iPLEX Gold Technology or allelic discrimination by real-time polymerase chain reaction (PCR). Homozygous carriers of the minor allele for both rs689466 and rs10935090 SNPs were associated with a 2.98 and 4.30-fold increased risk for GC, respectively (95% confidence interval (CI): 1.14\u20137.74, p = 0.027; 95% CI: 1.22\u201315.16, p = 0.026), with the latter also being associated with an anticipated diagnosis age. A multifactor dimensionality reduction analysis identified an overall three-factor best interactive model composed of age, rs689466, and rs1678374 that was associated with a 17.6-fold GC increased risk (95% CI: 11.67\u201326.48, p &lt; 0.0001, (cross-validation) CV consistency of 8\/10 and accuracy of 0.807). In this preliminary study, several tagSNPs in PGE2 pathway-related genes were identified as risk biomarkers for GC development. This approach may help to identify higher-risk individuals and may contribute to the tailoring screening of GC in intermediate-risk European countries.<\/jats:p>","DOI":"10.3390\/ijms22020648","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T11:36:11Z","timestamp":1610364971000},"page":"648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic Variations in Prostaglandin E2 Pathway Identified as Susceptibility Biomarkers for Gastric Cancer in an Intermediate Risk European Country"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0176-286X","authenticated-orcid":false,"given":"Catarina","family":"Lopes","sequence":"first","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research (CI-IPOP), Portuguese Institute of Oncology, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"given":"Carina","family":"Pereira","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research (CI-IPOP), Portuguese Institute of Oncology, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"CINTESIS\u2014Center for Health Technology and Services Research, University of Porto, Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]},{"given":"M\u00f3nica","family":"Farinha","sequence":"additional","affiliation":[{"name":"Pathology Department, Portuguese Institute of Oncology, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research (CI-IPOP), Portuguese Institute of Oncology, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"},{"name":"Portuguese League Against Cancer, Estrada Interior da Circunvala\u00e7\u00e3o, 4200-172 Porto, Portugal"}]},{"given":"M\u00e1rio","family":"Dinis-Ribeiro","sequence":"additional","affiliation":[{"name":"CINTESIS\u2014Center for Health Technology and Services Research, University of Porto, Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Gastroenterology Department, Portuguese Institute of Oncology, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6330","DOI":"10.18632\/oncotarget.14064","article-title":"Diagnostic and prognostic value of circulating tumor DNA in gastric cancer: A meta-analysis","volume":"8","author":"Gao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3748\/wjg.14.1149","article-title":"Role of symptoms in diagnosis and outcome of gastric cancer","volume":"14","author":"Maconi","year":"2008","journal-title":"World J. 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