Abstract 1870: Association of prostaglandin-endoperoxide synthase 2 (PTGS-2) polymorphisms with colorectal cancer risk and immunohistochemical detection of PTGS-2 in Chinese colorectal cancer patients

Abstract PTGS-2 is an rate-limiting enzyme that can be induced by several factors including mitogens, cytokines, growth factors and tumor promoters. It catalyzes the formation of Prostaglandin E2 (PGE2) that favors carcinogenic processes. Overexpression of PTGS-2 gene encoding PTGS-2 enzyme was observed in several human malignancies including colorectal cancer. Various functional genetic polymorphisms present in the PTGS-2 gene were shown to influence the expression level of the PTGS-2 protein and affect the individuals’ susceptibility to developing colorectal cancer. Whole gene screening in the healthy local Chinese subjects had identified 26 SNPs, which were tagged by 15 tag SNPs. Among these tag single nucleotide polymorphisms (SNPs), two were found in the 5′ upstream region [−1424 A>G (rs689465), −1329 A>G (rs689466)], five were in the intronic region [IVS1+145A>G (rs11567820), IVS2-22C>G (rs20427), IVS3+36C>T, IVS9+146C>T and IVS9-164G>T], two were in the coding region [306G>C (rs5277) and 1759G>A(rs3218625)], four were in the 3′ untranslated region (UTR) [*427T>C (rs5275), *2267G>T (rs4648302), *2358T>A (rs13306038), *2368_*2369insA] and two were located in the 3′ downstream region [*+2868G>A (rs4648308), *+4038_*4039insTA] of the PTGS-2 gene. This study aimed to investigate the association between fifteen PTGS-2 tag SNPs and one functional SNP [-899G>C (rs20417)] with (1) the risk of developing colorectal cancer and (2) the expression level of PTGS-2 protein in the tumor resections in Chinese colorectal cancer patients (N=90). The genetic association analysis indicated that patients harboring the heterozygous genotype (TC) of *427T>C (rs5275) SNP had a significant reduced risk in colorectal cancer predisposition (codominant model: Odds Ratio (OR)=0.51; 95% Confidence Interval (CI)=0.25-1.03; P=0.033 and overdominant model: OR=0.47; 95% CI=0.24-0.95; P=0.033). However, this SNP was not found to be significantly associated with the PTGS-2 expression in the tumor resections of the patients (N=48). No significant correlation was observed between other investigated tag SNPs with colorectal cancer risk and PTGS-2 protein expression. The findings of this study suggest that *427T>C (rs5275) might be a biomarker for colorectal cancer predisposition in the local Chinese colorectal cancer patients. Further conformational investigations in larger cohort should be performed to validate the findings of the present study. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1870. doi:1538-7445.AM2012-1870