PMID- 12208751
OWN - NLM
STAT- MEDLINE
DCOM- 20021003
LR  - 20231213
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 62
IP  - 17
DP  - 2002 Sep 1
TI  - A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is 
      associated with an increased risk of lung cancer.
PG  - 4992-5
AB  - DNA repair is central to genomic integrity. Reduced expression of several 
      nucleotide excision repair genes has been demonstrated to be associated with 
      increased risk of lung cancer. Because methylation of gene promoters is one of 
      the major regulatory mechanisms of gene expression and most nucleotide excision 
      repair gene promoters have not been fully characterized, we hypothesized that 
      genetic variants of the genes that are responsible for regulating genomic 
      methylation are associated with increased risk of lung cancer. Recently, we 
      identified a C-->T transition at a novel promoter region of cytosine 
      DNA-methyltransferase-3B (DNMT3B) and found that this polymorphic transition 
      significantly increases the promoter activity. In this hospital-based 
      case-control study of 319 patients with incident lung cancer and 340 healthy 
      controls frequency matched on age (+/-5 years), sex, ethnicity, and smoking 
      status, we genotyped subjects for this DNMT3B promoter polymorphism to determine 
      the association between this genetic variant and risk of lung cancer. Compared 
      with CC homozygotes, CT heterozygotes had a >2-fold increased risk of lung cancer 
      [adjusted odds ratio (OR), 2.13; 95% confidence interval (CI), 1.47-3.08] and TT 
      homozygotes an OR of 1.42 (95% CI, 0.91-2.21). The combined variant genotype (CT 
      + TT) was associated with a nearly 2-fold increased risk (adjusted OR, 1.88; 95% 
      CI, 1.32-2.66). These results suggest that this novel variant of DNMT3B is 
      associated with increased risk of lung cancer and may contribute to identifying 
      individuals genetically susceptible to tobacco-induced cancers. Additional 
      studies on the underlying molecular mechanism of this polymorphism are warranted.
FAU - Shen, Hongbing
AU  - Shen H
AD  - Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 
      Houston, Texas 77030, USA.
FAU - Wang, Luo
AU  - Wang L
FAU - Spitz, Margaret R
AU  - Spitz MR
FAU - Hong, Waun K
AU  - Hong WK
FAU - Mao, Li
AU  - Mao L
FAU - Wei, Qingyi
AU  - Wei Q
LA  - eng
GR  - CA 16672/CA/NCI NIH HHS/United States
GR  - CA 55769/CA/NCI NIH HHS/United States
GR  - CA 68437/CA/NCI NIH HHS/United States
GR  - CA 74851/CA/NCI NIH HHS/United States
GR  - CA 86390/CA/NCI NIH HHS/United States
GR  - ES 11740/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
SB  - IM
MH  - Aged
MH  - Alleles
MH  - Case-Control Studies
MH  - DNA (Cytosine-5-)-Methyltransferases/*genetics
MH  - Female
MH  - Humans
MH  - Logistic Models
MH  - Lung Neoplasms/enzymology/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Promoter Regions, Genetic
MH  - Risk Factors
MH  - Smoking
MH  - DNA Methyltransferase 3B
EDAT- 2002/09/05 10:00
MHDA- 2002/10/04 04:00
CRDT- 2002/09/05 10:00
PHST- 2002/09/05 10:00 [pubmed]
PHST- 2002/10/04 04:00 [medline]
PHST- 2002/09/05 10:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2002 Sep 1;62(17):4992-5.