Affiliations: [a] Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran | [b] Autoimmune Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Correspondence:
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Corresponding author: Fakhraddin Naghibalhossaini, Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Zand Street, Shiraz, Iran. Tel.: +98 711 2303029; Fax: +98 711 2303029; E-mail: fakhraddin.naghibalhossaini@mail.mcgill.ca
Abstract: OBJECTIVE: DNMT3B overexpression has been linked with the CpG
island methylator phenotype in various cancers. Considering the
role of the DNMT3b -149C/T promoter polymorphism on the gene expression, we
evaluated the associations of this polymorphism with colorectal cancer (CRC) risk and
hypermethylation of six tumor suppressor genes in CRC tumors. METHODS: The DNMT3b was genotyped by PCR-RFLP in 108 sporadic CRC
patients and 185 healthy controls and methylation of genes' promoter was
determined by methylation specific PCR. RESULTS: In comparison to controls, the TT genotype was strongly
associated with a high risk of cancer incidence (OR = 3.3, 95%
CI = 1.6-6.9). The frequency of methylated hMLH1 was significantly higher in
patients with the DNMT3b CT genotype (p= 0.03), especially in male
subjects. The frequency of hMLH1 methylation was significantly higher in young
patients (< 60 years) with the CT/TT genotypes. The combined CT/TT genotypes also showed significant
associations with the ECAD methylation in the entire group of patients
(p= 0.04), in patients with distal tumors, and in old cases. The DNMT3b
genotype was not associated with methylation of other genes examined in this study. CONCLUSIONS: Our results suggest that DNMT3b polymorphism is involved in
the development of colon cancer and non-random genes promoter methylation
among Iranian population.
