rs689466

This candidate gene association study of 370 CCA cases and 740 controls identified initial associations between COX-2 variants rs2143417 (OR=1.52) and rs689466 (OR=1.36) and cholangiocarcinoma risk; however, these findings failed replication in an independent cohort of 212 cases and 424 controls (rs2143417 OR=1.04, rs689466 OR=1.08). No SNP variants showed significant associations with CCA survival, and NKG2D variants previously reported to be associated with CCA did not replicate.

This document is a comprehensive collection of ~1,200 cancer-related research abstracts and summaries published in various journals (2013), covering clinical trials, pharmacogenomic studies, and mutation analyses across multiple cancer types including colorectal, breast, lung, lymphoma, and other malignancies. The collection documents associations between genetic variants (SNPs and somatic mutations), gene expression patterns, and cancer treatment outcomes, including studies on KRAS, EGFR, TP53, BRAF, and pharmacogenomic variants like CYP3A4 and UGT1A1.

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 is a comprehensive journal compilation containing multiple oncology and pharmacogenomics studies published in 2013 across various journals. The collection includes 60+ papers covering cancer treatment outcomes, genetic polymorphisms predicting chemotherapy response and survival, pharmacogenetic variants in drug metabolism and DNA repair genes, and prognostic biomarkers in various cancer types including breast, lung, colorectal, hematologic malignancies, and others. Key findings include associations of XRCC1 variants (rs915927, rs76507, rs2854501, rs2854509, rs3213255) with bladder cancer chemotherapy survival, ABCG2 rs2725264 with lung cancer overall survival (HR 3.22), SLCO1B1 rs4149056 with methotrexate pharmacokinetics, MTHFR rs1801131 with acute lymphoblastic leukemia outcome, and ABCC3/GSTM variants with acute myeloid leukemia survival.

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.

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.