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Article

Genetic Variations in Prostaglandin E2 Pathway Identified as Susceptibility Biomarkers for Gastric Cancer in an Intermediate Risk European Country

1
Molecular Oncology and Viral Pathology Group, IPO Porto Research (CI-IPOP), Portuguese Institute of Oncology, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
2
CINTESIS—Center for Health Technology and Services Research, University of Porto, Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal
3
Pathology Department, Portuguese Institute of Oncology, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
4
Portuguese League Against Cancer, Estrada Interior da Circunvalação, 4200-172 Porto, Portugal
5
Gastroenterology Department, Portuguese Institute of Oncology, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(2), 648; https://doi.org/10.3390/ijms22020648
Received: 14 November 2020 / Revised: 7 January 2021 / Accepted: 8 January 2021 / Published: 11 January 2021
(This article belongs to the Special Issue Genes, Environment and Cancer)
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® 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): 1.14–7.74, p = 0.027; 95% CI: 1.22–15.16, 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: 11.67–26.48, p < 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. View Full-Text
Keywords: gastric cancer; genetic susceptibility; prostaglandin E2; prostaglandin-endoperoxide synthase 2; hydroxyprostaglandin dehydrogenase 15-(NAD); solute carrier organic anion transporter family member 2A1; ATP binding cassette subfamily C member 4 gastric cancer; genetic susceptibility; prostaglandin E2; prostaglandin-endoperoxide synthase 2; hydroxyprostaglandin dehydrogenase 15-(NAD); solute carrier organic anion transporter family member 2A1; ATP binding cassette subfamily C member 4
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MDPI and ACS Style

Lopes, C.; Pereira, C.; Farinha, M.; Medeiros, R.; Dinis-Ribeiro, M. Genetic Variations in Prostaglandin E2 Pathway Identified as Susceptibility Biomarkers for Gastric Cancer in an Intermediate Risk European Country. Int. J. Mol. Sci. 2021, 22, 648. https://doi.org/10.3390/ijms22020648

AMA Style

Lopes C, Pereira C, Farinha M, Medeiros R, Dinis-Ribeiro M. Genetic Variations in Prostaglandin E2 Pathway Identified as Susceptibility Biomarkers for Gastric Cancer in an Intermediate Risk European Country. International Journal of Molecular Sciences. 2021; 22(2):648. https://doi.org/10.3390/ijms22020648

Chicago/Turabian Style

Lopes, Catarina, Carina Pereira, Mónica Farinha, Rui Medeiros, and Mário Dinis-Ribeiro. 2021. "Genetic Variations in Prostaglandin E2 Pathway Identified as Susceptibility Biomarkers for Gastric Cancer in an Intermediate Risk European Country" International Journal of Molecular Sciences 22, no. 2: 648. https://doi.org/10.3390/ijms22020648

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