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Single nucleotide polymorphism rs4648298 in miRNAs hsa-miR21 and hsa-miR590 binding site of COX gene is a strong colorectal cancer determinant.

ABSTRACT: Background:Genetic determinants are considered as driving forces in development colorectal cancer (CRC), a malignancy that ranks as the second cause of cancer death in the world. Single nucleotide polymorphisms (SNPs), are considered as the main genetic factor in cancers susceptibility. MicroRNAs are critical players in posttranslational gene regulation by binding to their specific recognition sequences located at 3' untranslated region (UTR) of mRNAs. In present study we have elucidated the role of 9,850 A?>?G (rs4648298), in development of sporadic CRC in Iranian population. Methods:A case-control study using 88 CRC patients and 88 noncancerous counterparts was undertaken in order to determine rs4648298 genotypes using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Also, a meta-analysis was performed based on 9 articles accessed via the MEDLINE, Cochrane review, Google Scholar and Scopus databases. Results:AA genotype was determined to be associated with significant decreased risk of CRC in our study population [odds ratio (OR) =0.14; 95% confidence interval (CI), 0.05-0.34; P<0.001]. In a meta-analysis on 6 risk estimates for the AG versus AA genotype, we found a significant inverse association between AG SNPs and risk of gastric adenocarcinoma, CRC, breast cancer and prostate cancer (OR =0.86; 95% CI, 0.76-0.98; P<0.02). Conclusions:Our results suggest significant correlation between rs4648298 polymorphism and CRC risk in Iranian population.

SUBMITTER: Mosallaei M

PROVIDER: S-EPMC6006039 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Single nucleotide polymorphism rs4648298 in miRNAs hsa-miR21 and hsa-miR590 binding site of <i>COX</i> gene is a strong colorectal cancer determinant.

Mosallaei Meysam M Simonian Miganoosh M Ahangari Fateme F Miraghajani Maryam M Mortazavi Deniz D Salehi Ahmad Reza AR Khosravi Sharifeh S Salehi Rasoul R

Journal of gastrointestinal oncology 20180601 3

<h4>Background</h4>Genetic determinants are considered as driving forces in development colorectal cancer (CRC), a malignancy that ranks as the second cause of cancer death in the world. Single nucleotide polymorphisms (SNPs), are considered as the main genetic factor in cancers susceptibility. MicroRNAs are critical players in posttranslational gene regulation by binding to their specific recognition sequences located at 3' untranslated region (UTR) of mRNAs. In present study we have elucidated ...[more]

PMID: 29998010

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Project description:PURPOSE:Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2; a target of aspirin) produces inflammatory mediator prostaglandin E2 (PGE2), and contributes to colorectal neoplasia development. PTGS2-driven inflammatory responses can induce tumor expression of microRNA MIR21 (miR-21) that can increase local PGE2 level by downregulating PGE2-metabolizing enzymes. We hypothesized that the prognostic association of tumor MIR21 expression level in colorectal carcinoma might depend on inflammatory tumor microenvironment and be stronger in tumors expressing high-level PTGS2. EXPERIMENTAL DESIGN:Utilizing 765 rectal and colon cancer specimens in the Nurses' Health Study and the Health Professionals Follow-up Study, we measured MIR21 expression by quantitative reverse transcription PCR, and PTGS2 expression by immunohistochemistry. Cox proportional hazards regression model was used to assess statistical interaction between MIR21 and PTGS2 in colorectal cancer-specific survival analysis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutations. RESULTS:Tumor MIR21 expression level was associated with higher colorectal cancer-specific mortality (Ptrend = 0.029), and there was a statistically significant interaction between MIR21 and PTGS2 (Pinteraction = 0.0004). The association between MIR21 expression and colorectal cancer-specific mortality was statistically significant in PTGS2-high cancers (multivariable hazard ratio of the highest vs. lowest quartile of MIR21, 2.28; 95% confidence interval, 1.42-3.67; Ptrend = 0.0004) but not in PTGS2-absent/low cancers (Ptrend = 0.22). CONCLUSIONS:MIR21 expression level in colorectal carcinoma is associated with worse clinical outcome, and this association is stronger in carcinomas expressing high-level PTGS2, suggesting complex roles of immunity and inflammation in tumor progression. Clin Cancer Res; 22(15); 3841-8. ©2016 AACR.

Dataset Information

Single nucleotide polymorphism rs4648298 in miRNAs hsa-miR21 and hsa-miR590 binding site of COX gene is a strong colorectal cancer determinant.

Publications

Single nucleotide polymorphism rs4648298 in miRNAs hsa-miR21 and hsa-miR590 binding site of <i>COX</i> gene is a strong colorectal cancer determinant.

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