title: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Micro RNA-375 and rs4939827 SNP in SMAD7 could be considered as potential markers for detecting and early diagnosing CRC patients.
authors.affiliation: Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Olfat Gamil
authors.identifier: http://orcid.org/0000-0002-3031-3599
authors.initials: OG
authors.lastname: Shaker
authors.affiliation: Departments of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Al Fayoum, Egypt.
authors.forename: Shereen Rashad
authors.initials: SR
authors.lastname: Mohammed
authors.affiliation: Departments of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Al Fayoum, Egypt.
authors.forename: Asmaa Mohammed
authors.initials: AM
authors.lastname: Mohammed
authors.affiliation: Departments of Tropical Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Mahmoud
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051906:Smad7 Protein / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: C540933:MIRN375 microRNA, human; D035683:MicroRNAs; C497806:SMAD7 protein, human; D051906:Smad7 Protein
keywords: SMAD-7gene polymorphisms; colorectal cancer; microRNA-375