Association study of functional polymorphisms of DNMT3A and DNMT3B genes with breast carcinoma in north Indian population

Abstract

DNMT3A and DNMT3B are de novo methyltransferases which are responsi-ble for de novo methylation patterns of the unmethylated DNA. Two Single nucleotide polymorphisms (SNPs) in these genes i.e. -448A>G in DNMT3A and C46359T in DNMT3B, contribute a lot to the genetic susceptibility to breast cancer. In the present study, we analyzed the genotype frequencies of -448A>G polymorphism of DNMT3A and C46359T polymorphism of DNMT3B in breast cancer patients and healthy control subjects to explore the associa-tion of these single nucleotide polymorphisms with susceptibility to develop breast carcinoma. Genotyping was done by PCR-RFLP. 74 patients and 76 controls were genotyped for the DNMT3A (-448A>G) SNP, whereas 72 pa-tients and 107 controls were screened for DNMT3B (C46359T) polymor-phism. Our study clearly suggest that compared to GG carriers, the DNMT3A-448AA homozygotes had a 2.92 fold risk of developing breast carcinoma whereas for DNMT3B (C46359T) polymorphism, CT & CT+CC genotype carri-ers showed a 1.32 & 1.23 fold risk of developing breast carcinoma respec-tively. In Conclusion, DNMT3A SNP -448A>G contributes to genetic suscepti-bility to breast carcinoma whereas DNMT3B SNP C46359T was not found to be associated with pathogenesis of breast cancer in north Indian population.