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Genotypes and haplotypes of the methyl-CpG-binding domain 2 modify breast cancer risk dependent upon menopausal status.

Abstract：

INTRODUCTION:MBD2, 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. METHODS:DNA 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. RESULTS:The 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. CONCLUSION:Our 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.

journal_name

Breast Cancer Res

journal_title

Breast cancer research : BCR

authors

Zhu Y,Brown HN,Zhang Y,Holford TR,Zheng T

doi

10.1186/bcr1283

keywords:

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

R745-52

issue

5

eissn

1465-5411

issn

1465-542X

pii

bcr1283

journal_volume

7

pub_type

杂志文章

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