Association between the 8473T>C Polymorphism of <b><i>PTGS2</i></b> and Prostate Cancer Risk: A Metaanalysis Including 24,716 Subjects

Abstract

Background: Prostaglandin endoperoxide synthase 2 (PTGS2) is involved in prostate cancer (PCa) by stimulating cell proliferation, promoting angiogenesis, inhibiting apoptosis, and mediating immune suppression. 8473T>C, located in the 3' UTR of the PTGS2 gene, has been considered to influence PCa risk. Methods: We searched Medline, PubMed, Elsevier, and Web of Science (updated to February 5, 2012) using the following search terms: ‘8473T>C' or ‘rs5275', ‘genetic variant' or ‘polymorphism', ‘prostate cancer', ‘cancer', ‘PTGS2' or ‘COX-2'. Odds ratios with 95% confidence intervals were assessed by using fixed or random effect models. Both funnel plot and Egger's test were used to assess the publication bias. Results: Finally, 5 case control studies were included. Overall, no evidence was observed of a relationship between the 8473T>C and PCa risk in any genetic model. No significant association was found in the studies whose controls conform to the Hardy-Weinberg equilibrium. In the stratified analysis, significant association was detected in other populations (except for Caucasians), which were based on hospitals. Conclusion: The 8473T>C polymorphism may have little association with PCa risk among Caucasians, but might be involved in PCa risk in other ethnicities. Nevertheless, more well-designed studies with a larger sample size including different ethnicities should be conducted.

Prostate cancer: from the pathophysiologic implications of some genetic risk factors to translation in personalized cancer treatments

“…7 Furthermore, several recently published studies have demonstrated significant associations of SNPs in the PTGS2 gene with PC risk. 7,20,37 However, different results have been obtained. 7,20,37 Nevertheless, COX-2 remains a molecule of particular interest in the link between inflammation and PC.…”

COX-2 rs689466, rs5275, and rs20417 polymorphisms and risk of head and neck squamous cell carcinoma: a meta-analysis of adjusted and unadjusted data

“…The human cyclooxygenase-2 (COX-2), the key enzyme in the conversion of arachidonic acid to prostatglandins, is located at chromosome 1q25.2-q25.3 and rs20417 (−765G > C), rs689466 (−1195G > A), and rs5275 (8473 T > C) are the three commonly investigated polymorphisms in the COX-2 gene [ 14 , 15 ]. Now the association between COX-2 gene polymorphisms and risk of many cancers, such as hepatocellular carcinoma [ 16 ], colorectal cancer [ 17 ], breast cancer [ 18 ], prostate cancer [ 19 ], gastric cancer [ 20 ] were investigated by meta-analyses. COX-2 has been confirmed very low or no expression in normal human oral tissues, otherwise it was elevated in oral precancerous lesions and over-expressed in oral squamous cell carcinoma (OSCC) [ 21 ].…”

Prognostic Value of Prostaglandin-endoperoxide Synthase 2 Polymorphisms in Prostate Cancer Recurrence after Radical Prostatectomy

“…More evidence indicates that ethnic background and family history are associated with the risk of prostate cancer, suggesting genetic susceptibility in prostate cancer predisposition 6 . Several single-nucleotide polymorphisms (SNPs) of PTGS2 are associated with susceptibility to prostate cancer 7 - 9 , but no study to date has examined their ability to predict disease progression. Therefore, the aim of this study was to systematically evaluate the prognostic significance of PTGS2 SNPs on BCR in localized prostate cancer patients after RP.…”