Impact of microRNA-375 and its target gene SMAD-7 polymorphism on susceptibility of colorectal cancer

Abstract

Background: Colorectal cancer (CRC) has a high morbidity and mortality. Many studies reported that mir-375 is frequently down-regulated in many cancers including esophageal cancer, hepatocellular carcinoma, breast cancer and leukemias.

Aim: Our aim was to study the expression of microRNA-375 and its target gene SMAD-7 polymorphisms (rs4939827) in CRC patients in comparison to control subjects and to correlate these results with clinical data of patients to elucidate their role in pathogenesis and early diagnosis of CRC.

Material and methods: The present study was conducted on 122 subjects divided into 86 patients with CRC and 36 age- and sex-matched controls. The followings were done to all subjects: full history taking, full clinical examination, complete blood picture, serum (ALT, AST), serum albumin, CEA, TLC, PLT, and creatinine. Gene expression of miRNA-375 from serum was done by real-time PCR. Gene polymorphism SNPs of SMAD7 (rs4939827) was also done in DNA extracted from blood by real-time PCR.

Results: As regards the polymorphism of SMAD7, we found that CC (wild) genotype has high percentage in controls compared to CRC cases (36.1% vs 15.1%). Meanwhile, the mutant and heterozygotes genotypes showed high percentage among cases compared to controls (33.7%, and 51.2% respectively) vs (22.2%, and 41.7% respectively) with no significant statistical analysis. There was a statistically significant high T-allelic frequency among cases and C-allelic frequency among controls. There was a statistically significant association between fold change in micro RNA (-375) and the susceptibility to CRC as there is down-regulation of the microRNA-375 in CRC group with fold change in 0.42±0.27.

Conclusion: Micro RNA-375 and rs4939827 SNP in SMAD7 could be considered as potential markers for detecting and early diagnosing CRC patients.

Keywords: SMAD-7gene polymorphisms; colorectal cancer; microRNA-375.