title: Genotypes and haplotypes of the methyl-CpG-binding domain 2 modify breast cancer risk dependent upon menopausal status.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA. yong.zhu@yale.edu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Heather N
authors.initials: HN
authors.lastname: Brown
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holford
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008593:Menopause; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D018570:Risk Assessment
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C489325:MBD2 protein, human