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.
CINTESIS-Center for Health Technology and Services Research, University of Porto, Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal.
Int J Mol Sci. 2021 Jan 11;22(2):648. doi: 10.3390/ijms22020648.
The cyclooxygenase-2 (COX-2)/prostaglandin E (PGE) pathway exerts deleterious pleiotropic effects in inflammation-induced gastric carcinogenesis. We aimed to assess the association of genetic variants in prostaglandin-endoperoxide synthase 2 (), ATP binding cassette subfamily C member 4 (), hydroxyprostaglandin dehydrogenase 15-(NAD) ), and solute carrier organic anion transporter family member 2A1 () PGE 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, = 0.027; 95% CI: 1.22-15.16, = 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, < 0.0001, (cross-validation) CV consistency of 8/10 and accuracy of 0.807). In this preliminary study, several tagSNPs in PGE 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.
环氧合酶-2（COX-2）/前列腺素 E（PGE）途径在炎症诱导的胃癌发生中发挥有害的多效性作用。我们旨在评估前列腺素内过氧化物合酶 2（）、ATP 结合盒亚家族 C 成员 4（）、羟前列腺素脱氢酶 15-（NAD））和溶质载体有机阴离子转运体家族成员 2A1（）PGE 途径相关基因中的遗传变异与欧洲白种人群胃癌（GC）风险之间的关联。进行了一项基于医院的病例对照研究，共收集了 260 例 GC 病例和 476 例无癌症对照。使用标记 SNP 方法，通过 MassARRAY iPLEX Gold Technology 或实时聚合酶链反应（PCR）的等位基因鉴别对 51 个单核苷酸多态性（SNP）进行基因分型。rs689466 和 rs10935090 两个 SNP 的杂合子携带者患 GC 的风险分别增加了 2.98 倍和 4.30 倍（95%置信区间（CI）：1.14-7.74， = 0.027；95%CI：1.22-15.16， = 0.026），后者也与预期的诊断年龄相关。多因子降维分析确定了一个由年龄、rs689466 和 rs1678374 组成的总体三因子最佳交互模型，该模型与 17.6 倍的 GC 风险增加相关（95%CI：11.67-26.48， < 0.0001，（交叉验证）CV 一致性为 8/10，准确性为 0.807）。在这项初步研究中，确定了 PGE 途径相关基因中的几个标记 SNP 作为 GC 发展的风险生物标志物。这种方法可以帮助识别高风险个体，并有助于在欧洲中等风险国家进行 GC 的定制筛查。
