Methyl-CpG-binding domain 2: a protective role in bladder carcinoma.
BACKGROUND
MBD2, a methyl-CpG-binding domain 2 protein, has attracted much attention because of its role in epigenetic regulation of gene expression. In addition to transcriptional repression, MBD2 has also been shown to catalyze demethylation by directly removing methyl groups from 5-methylcytosine residues in DNA. Although the demethylase activity of MBD2 remains controversial, reduction of MBD2 messenger RNA expression has been observed in various tumor tissue types. In the current case-control study, the authors investigated the association between MBD2 expression and bladder carcinoma risk.


METHODS
RNA was isolated from the peripheral blood lymphocytes of 98 bladder carcinoma case patients and 135 frequency-matched control patients. MBD2 expression was measured by real-time quantitative reverse transcription-polymerase chain reaction assays.


RESULTS
Overall, there was a significantly reduced risk associated with high levels of MBD2 expression (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.21-0.90). This relation was maintained when the data were categorized according to quartile distribution for MBD2 expression (P for trend < 0.05). It is noteworthy that the protective effects were more apparent in women (OR, 0.25; 95% CI, 0.06-1.02) compared with men (OR, 0.58; 95%; CI, 0.24-1.42), in older individuals (OR, 0.12; 95% CI, 0.03-0.45) compared with younger individuals (OR, 1.16; 95% CI, 0.40-3.33), and in heavier smokers (OR, 0.40; 95% CI, 0.18-0.93) compared with lighter smokers (OR, 0.71; 95% CI, 0.18-2.86).


CONCLUSIONS
Although the underlying molecular mechanisms remain unclear, the data obtained in the current study represent the first evidence demonstrating a protective role against bladder carcinoma risk for MBD2. MBD2 expression may prevent age-related, gender-related, and smoking-induced hypermethylation, which are predisposing factors for tumor development.
Zhu
Yong
Y
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Spitz
Margaret R
MR
Zhang
Hui
H
Grossman
H Barton
HB
Frazier
Marsha L
ML
Wu
Xifeng
X
D001483:Base Sequence; D016022:Case-Control Studies; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008969:Molecular Sequence Data; D016017:Odds Ratio; D011336:Probability; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control
D004268:DNA-Binding Proteins; C115368:MBD2 protein; D012333:RNA, Messenger