Vera Chayeb1, Sana Mahjoub2, Hedia Zitouni3, Hanene Jrah-Harzallah2, Khadija Zouari4, Rached Letaief5, Touhami Mahjoub2. 1. Faculty of Science of Bizerte, University of Carthage, Tunisia; Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Tunisia. Electronic address: vchaieb@yahoo.fr. 2. Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Tunisia. 3. Faculty of Science of Bizerte, University of Carthage, Tunisia; Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Tunisia. 4. Research Unit "Colorectal cancer of the Young subject (05/UR/08-15)", Faculty of Medicine of Monastir, University of Monastir, Tunisia; General Surgery Department, Fattouma Bourguiba, University Hospital of Monastir, Tunisia. 5. General Surgery Department, Farhat Hached, University Hospital of Sousse, Tunisia.
Abstract
BACKGROUND AND AIM: Colorectal cancer (CRC) is a worldwide leading cause of mortality. Genetic studies have associated single nucleotide polymorphisms in genes encoding microRNAs with CRC risk but results are mostly inconclusive across variable ethnicities. In this study, we investigated the association of hsa-mir-149 rs2292832 C/T, hsa-mir-146a rs2910164 G/C and hsa-mir-196a2 rs11614913 C/T and explored their roles in clinicopathological features of CRC progression in an Eastern Tunisian cohort. SUBJECTS AND METHODS: Three hundred thirteen subjects were enrolled in our retrospective study including 152 CRC cases and 161 controls. Genotyping was assayed by RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction) method. SPSS v.18.0, R and SNP Stats online software performed statistical analysis. RESULTS: Significantly higher hsa-mir-149C/T rs2292832 minor allele frequency was associated with increased risk of CRC [p = .03; OR = 1.54 (1.08-2.19)]. In addition, significant crude associations of hsa-mir-149C/T rs2292832 polymorphism were detected under codominant, dominant and additive models of inheritance. After adjusting for covariates and performing FDR correction, these associations did not remain. No associations were detected for hsa-mir-146a G/C rs2910164 and hsa-mir-196a2 C/T rs11614913. When performing stratified analysis of clinicopathological features according to genotypes, a significant association (p = .004) was found between hsa-mir-146a G/C rs2910164 and tumour differentiation grade. Regression analysis according to CRC progression features had demonstrated a trend toward significance in overdominant model of inheritance for hsa-mir-149C/T rs2292832 with a protective effect [p = .05; OR = 0.51 (0.26-1.02)]. CONCLUSION: Hsa-mir-149C/T rs2292832 and hsa-mir-146a G/C rs2910164 may influence CRC risk in an ethnicity-dependent manner by interfering with CRC progression parameters in Tunisian cohort.
BACKGROUND AND AIM: Colorectal cancer (CRC) is a worldwide leading cause of mortality. Genetic studies have associated single nucleotide polymorphisms in genes encoding microRNAs with CRC risk but results are mostly inconclusive across variable ethnicities. In this study, we investigated the association of hsa-mir-149 rs2292832 C/T, hsa-mir-146a rs2910164 G/C and hsa-mir-196a2 rs11614913 C/T and explored their roles in clinicopathological features of CRC progression in an Eastern Tunisian cohort. SUBJECTS AND METHODS: Three hundred thirteen subjects were enrolled in our retrospective study including 152 CRC cases and 161 controls. Genotyping was assayed by RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction) method. SPSS v.18.0, R and SNP Stats online software performed statistical analysis. RESULTS: Significantly higher hsa-mir-149C/T rs2292832 minor allele frequency was associated with increased risk of CRC [p = .03; OR = 1.54 (1.08-2.19)]. In addition, significant crude associations of hsa-mir-149C/T rs2292832 polymorphism were detected under codominant, dominant and additive models of inheritance. After adjusting for covariates and performing FDR correction, these associations did not remain. No associations were detected for hsa-mir-146a G/C rs2910164 and hsa-mir-196a2 C/T rs11614913. When performing stratified analysis of clinicopathological features according to genotypes, a significant association (p = .004) was found between hsa-mir-146a G/C rs2910164 and tumour differentiation grade. Regression analysis according to CRC progression features had demonstrated a trend toward significance in overdominant model of inheritance for hsa-mir-149C/T rs2292832 with a protective effect [p = .05; OR = 0.51 (0.26-1.02)]. CONCLUSION: Hsa-mir-149C/T rs2292832 and hsa-mir-146a G/C rs2910164 may influence CRC risk in an ethnicity-dependent manner by interfering with CRC progression parameters in Tunisian cohort.