rs5275

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

This functional study examined how PTGS2 gene variants in the promoter region and 3'-UTR modulate COX-2 gene expression using luciferase reporter assays in MCF-7 and HEK293FT cells. The rs689466 G variant showed consistent enhancing effects (~2-fold increase in transcriptional activity, P<0.001), while rs20417 C reduced activity by 40% in MCF-7 cells. The 3'-UTR rs5275 variant had variable effects depending on cell line, but the transcriptional effect of rs689466 remained detectable.

This association study of 377 Korean colorectal cancer patients examined 15 SNPs in 12 apoptosis-related genes as prognostic markers for survival after curative resection. RIPK1 rs2272990 (GA/AA genotype, HR=2.093, p=0.007) and CASP7 rs2227310 (GG genotype, HR=2.641, p=0.002) were significantly associated with worse disease-free survival in multivariate analysis, with similar associations for disease-specific survival. The polymorphisms showed stronger associations in colon cancer than rectal cancer.

A case-control study of 326 cases and 748 controls identified 25 SNPs in genes involved in platelet activation, angiogenesis, and inflammatory response that modify the risk of aspirin-related upper gastrointestinal hemorrhage (UGIH). Seven SNPs (rs1387180, rs2238631, rs1799964, rs5050, rs689466, rs1799983, rs7756935) were positive modifiers increasing UGIH risk in aspirin users (RERI 1.75-4.95), while nine SNPs (rs2243086, rs1131882, rs4311994, rs10120688, rs4251961, rs3778355, rs1330344, rs5275, rs3779647) were negative modifiers reducing risk (RERI -2.74 to -0.95). Aspirin exposure alone increased UGIH risk approximately 5.82-fold (95% CI: 2.2-10.08).

This review examines COX-2 (PTGS2) genetic variants and their association with gastric cancer susceptibility. Key variants include rs689466 (OR=1.19, p=0.002), rs20417 (OR=1.26, p<0.001), rs3218625 (OR=1.62, p=0.039), and rs5275 (OR=1.14, p=0.030), which increase gastric cancer risk through enhanced transcriptional activity or mRNA stability. The paper synthesizes data from multiple case-control studies and the authors' own analyses in Chinese populations (296-660 cases each), establishing COX-2 polymorphisms as potential biomarkers for cancer risk stratification.

A case-control association study of 240 early breast cancer patients examining 12 SNPs in apoptosis-related genes found that TNFSF10 rs1131532 (F275F) was significantly associated with poor survival outcomes, with the TT genotype showing worse disease-free survival (HR = 3.304, P = 0.002), distant disease-free survival (HR = 4.757, P = 0.001), and overall survival (HR = 4.691, P = 0.002). PTGS2 rs5275 was also associated with distant disease-free survival (HR = 0.302, P = 0.041).

In 90 DLBCL patients treated with R-CHOP chemotherapy, polymorphisms in apoptosis-related genes were analyzed. The AA genotype of LTA C804A (rs1041981) was associated with worse time to progression (HR = 7.92; 95% CI = 1.42-44.18; P = 0.018), as was the GG genotype of RIPK1 G83A (rs2272990) (HR = 20.02; 95% CI = 1.59-251.52; P = 0.018). These polymorphisms may serve as prognostic markers for DLBCL treated with R-CHOP.

A case-control study of 147 oral premalignant lesion (OPL) patients and 147 healthy controls found that the COX-2 exon10+837T>C variant (rs5275) was associated with significantly reduced OPL risk (OR=0.48, 95% CI 0.28-0.80, p=0.005). Common haplotype WMW (containing the rs5275 variant) and diplotype WWW/WMW both showed reduced OPL risk (ORs 0.55 and 0.44, respectively), with protective effects observed in males, younger subjects, ever smokers, and ever drinkers.

This study analyzed 15 apoptosis-related gene polymorphisms in 76 patients with metastatic colorectal cancer treated with capecitabine and oxaliplatin chemotherapy. The PTGS2 8473T>C (rs5275) polymorphism was found to be significantly associated with progression-free survival (p=0.038, HR=2.19, dominant model p=0.046) and overall survival (p=0.040, dominant model p=0.013) in multivariate Cox regression analysis.

This case-control study identified a novel COX-2 exon 10 SNP (1759G>A, rs3218625) that causes a Gly587Arg amino acid substitution. Functional assays demonstrated that COX-2-587Arg has significantly higher enzymatic activity toward arachidonic acid (13.8 vs 11.2 U/mg, P=0.012). In 1,026 esophageal squamous-cell carcinoma patients and 1,270 controls, individuals carrying the 1759A allele had increased ESCC risk (OR=1.91, 95% CI=1.39-2.62, P<0.0001), with heterozygotes showing an OR of 1.87 (95% CI=1.36-2.57).

A case-control study in Brazilian women investigating the association between PTGS2 (COX-2) gene polymorphisms and breast cancer risk. The study identified nine SNPs in the promoter and 3'-UTR regions, with four frequent SNPs (rs689465, rs689466, rs20417, rs5275) selected for analysis. While rs5275 TC heterozygotes showed increased frequency in cases (OR=1.44, P=0.043), the authors concluded there was no strong association between the most frequent PTGS2 SNPs and breast cancer risk.

This association study identified five SNPs in the PTGS2 gene (cyclooxygenase-2) and tested their association with type 2 diabetes mellitus (T2DM) in approximately 1,000 Pima Indians. Two promoter/intronic variants were significantly associated with T2DM: rs20417 (OR=1.6 per C allele copy, P=0.01) and rs2066826 (OR=1.5 per T allele copy, P=0.01), with individuals carrying variant alleles showing 30% higher diabetes prevalence. The rs20417 C allele variant has been shown to reduce PTGS2 promoter activity, suggesting a biological mechanism through altered gene expression affecting insulin secretion.