Abstract
IntroductionMBD2, the gene encoding methyl-CpG-binding domain (MBD)2, is a major methylation related gene and functions as a transcriptional repressor that can specifically bind to the methylated regions of other genes. MBD2 may also mediate gene activation because of its potential DNA demethylase activity. The present case-control study investigated associations between two single nucleotide polymorphisms (SNPs) in the MBD2 gene and breast cancer risk.MethodsDNA samples from 393 Caucasian patients with breast cancer (cases) and 436 matched control individuals, collected in a recently completed breast cancer case–control study conducted in Connecticut, were included in the study. Because no coding SNPs were found in the MBD2 gene, one SNP in the noncoding exon (rs1259938) and another in the intron 3 (rs609791) were genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate cancer risk associated with the variant genotypes and the reconstructed haplotypes.ResultsThe variant genotypes at both SNP loci were significantly associated with reduced risk among premenopausal women (OR = 0.41 for rs1259938; OR = 0.54 for rs609791). Further haplotype analyses showed that the two rare haplotypes (A-C and A-G) were significantly associated with reduced breast cancer risk (OR = 0.40, 95% CI = 0.20–0.83 for A-C; OR = 0.47, 95% CI = 0.26–0.84 for A-G) in premenopausal women. No significant associations were detected in the postmenopausal women and the whole population.ConclusionOur results demonstrate a role for the MBD2 gene in breast carcinogenesis in premenopausal women. These findings suggest that genetic variations in methylation related genes may potentially serve as a biomarker in risk estimates for breast cancer.
Highlights
MBD2, the gene encoding methyl-CpG-binding domain (MBD)2, is a major methylation related gene and functions as a transcriptional repressor that can bind to the methylated regions of other genes
Further haplotype analyses showed that the two rare haplotypes (A-C and A-G) were significantly associated with reduced breast cancer risk (OR = 0.40, 95% confidence intervals (CIs) = 0.20– 0.83 for A-C; Odds ratios (ORs) = 0.47, 95% CI = 0.26–0.84 for A-G) in premenopausal women
Our results demonstrate a role for the MBD2 gene in breast carcinogenesis in premenopausal women
Summary
MBD2, the gene encoding methyl-CpG-binding domain (MBD), is a major methylation related gene and functions as a transcriptional repressor that can bind to the methylated regions of other genes. The present case-control study investigated associations between two single nucleotide polymorphisms (SNPs) in the MBD2 gene and breast cancer risk. Dysregulated epigenetic controls, which usually are represented by abnormal DNA methylation patterns such as global hypomethylation and region specific hypermethylation, are a hallmark of most cancers. Given the epigenetic role of MBD proteins in regulating gene expression, MBDs may be involved in cancer development by affecting the expression of cancer related genes. There is growing evidence that aberrant expression of MBD proteins is associated with human cancers [8,9]
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