A Meta-Analysis of <i>PTGS1</i> and <i>PTGS2</i> Polymorphisms and NSAID Intake on the Risk of Developing Cancer

<div><p>Background</p><p>Several studies have investigated whether the polymorphisms in the prostaglandin endoperoxide synthase 1 (<i>PTGS1</i>) and <i>PTGS2</i> genes and nonsteroidal anti-inflammatory drug (NSAID) use are associated with cancer risk; however, those studies have produced mixed results. Therefore, we performed a meta-analysis to evaluate the association between the <i>PTGS1</i> and <i>PTGS2</i> polymorphisms and the effect of NSAID use on the risk of developing cancer.</p><p>Methods</p><p>We conducted a comprehensive search in PubMed through March 2012. The odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated using the fixed-effect model or the random-effect model.</p><p>Results</p><p>The database search generated 13 studies that met the inclusion criteria. For <i>PTGS1</i> rs3842787, NSAID users homozygous for the major allele (CC) had a significantly decreased cancer risk compared with non-NSAID users (OR = 0.73, 95% CI = 0.59–0.89). For <i>PTGS2</i> rs5275 and rs20417, there were no significant differences between the gene polymorphism and NSAID use on cancer risk among the 8 and 7 studies, respectively. However, in the stratified analysis by the type of cancer or ethnicity population, NSAID users homozygous for the major allele (TT) in rs5275 demonstrated significantly decreased cancer risk compared with non-NSAID users in cancer type not involving colorectal adenoma (OR = 0.70, 95% CI = 0.59–0.83) and among the USA population (OR = 0.67, 95% CI = 0.56–0.82). NSAID users homozygous for the major allele (GG) in rs20417 displayed a significantly decreased cancer risk than non-NSAID users among the US population (OR = 0.72, 95% CI = 0.58–0.88). For the <i>PTGS2</i> rs689466 and rs2745557 SNPs, there were no significant differences.</p><p>Conclusion</p><p>This meta-analysis suggests that the associations between <i>PTGS</i> polymorphisms and NSAID use on cancer risk may differ with regard to the type of cancer and nationality.</p>