Single nucleotide polymorphism in DNMT3B promoter and its association with hepatocellular carcinoma in a Moroccan population

Abstract

Hepatocellular carcinoma is a major malignant tumor characterized in all areas by the disparity of risk between genders. The molecular bases of such disparity are still poorly understood. DNA-methyltransferase-3B (DNMT3B) may play an oncogenic role during tumorigenesis, and its genetic variants have been consistently associated with risk of several cancers, but a single study has investigated their roles in hepatocellular carcinoma (HCC). Polymorphisms of the DNMT3B gene may influence its activity on DNA methylation in several cancers, thereby modulating susceptibility to tumorigenesis. To test this hypothesis, we investigated the association between single nucleotide polymorphism -149C > T (rs2424913) in the promoter region DNMT3B and risk of HCC in a Moroccan population. In this case-control study, the DNMT3B SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism in 96 HCCs patients and 222 healthy controls that matched for age, sex and ethnicity. Overall, we found that, the DNMT3B 149 TT genotype was not significantly associated with increased risk of HCC (adjusted odds ratio (OR), 0.86, 95% CI, 0.41-1.80, P = 0.697). Stratification analysis detected, however, a trend towards a profound risk in the female subset of patients (OR = 2.04, 95% CI, 0.77-5.42) and a lesser risk for HCV-infected patients (OR = 1.33, 95% CI, 0.43-4.17). Our findings contrast with those of previous studies performed in various cancers, which showed that individuals carrying at least one T allele have a significantly increased risk of developing cancer. In addition, we provide genetic evidence for the major difference of HCC risk between men and women. Further mechanistic studies are needed to unravel the underlying molecular mechanisms. © 2009 Elsevier B.V. All rights reserved.