Genetic variation in the promoter of DNMT3B is associated with the risk of colorectal cancer

Abstract

Purpose: DNA methyltransferase-3B (DNMT3B) plays an important role in the generation of aberrant methylation in carcinogenesis. Polymorphisms of the DNMT3B gene may influence DNMT3B enzyme activity on DNA methylation, thereby modulating the susceptibility to colorectal cancer (CRC). Methods: The polymorphisms in the promoter region of the DNMT3B gene [-149C>T (rs2424913) and -579G>T (rs1569686)] were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and a total of 544 CRC patients and 533 age- and sex-matched healthy controls were enrolled in the case-control study. Results: The results showed that the -579G allele was associated with a significantly decreased risk of CRC (adjusted OR, 0.50; 95%CI, 0.35-0.72; P = 0.0002) when compared with the -579TT genotype. However, the DNMT3B-149CT genotype was not associated with the risk of CRC (adjusted OR, 0.48; 95%CI, 0.18-1.30; P = 0.151). In addition, stratification analysis revealed that the increased risk was predominant in both colon cancer and rectal cancer showing no effect of primary occurrence site. Conclusion: Our research demonstrated the -579G allele was a potential protective factor for the occurrence of CRC. © 2011 Springer-Verlag.