PMID- 15528220
OWN - NLM
STAT- MEDLINE
DCOM- 20050310
LR  - 20231213
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 26
IP  - 2
DP  - 2005 Feb
TI  - DNMT3B polymorphisms and risk of primary lung cancer.
PG  - 403-9
AB  - DNA-methyltransferase-3B (DNMT3B) plays an important role in the generation of 
      aberrant methylation in carcinogenesis. Polymorphisms and haplotypes of the 
      DNMT3B gene may influence DNMT3B activity on DNA methylation, thereby modulating 
      the susceptibility to lung cancer. To test this hypothesis, we investigated the 
      association of the -283T > C (from exon 1A transcription start site) and -579G > 
      T (from exon 1B transcription start site) polymorphisms in DNMT3B promoter, and 
      their haplotypes with the risk of lung cancer in a Korean population. The DNMT3B 
      genotype was determined in 432 lung cancer patients and 432 healthy controls that 
      were frequency-matched for age and sex. Individuals with at least one -283T 
      allele were at a significantly decreased risk of adenocarcinoma (AC) and small 
      cell carcinoma (SM) [adjusted odds ratio (OR) = 0.48, 95% confidence interval 
      (CI) = 0.28-0.82, P = 0.007; and adjusted OR = 0.47, 95% CI = 0.24-0.93, P = 
      0.03, respectively] compared with those harboring a -283CC genotype. Individuals 
      with at least one -579G allele were also at a significantly decreased risk of AC 
      and SM (adjusted OR = 0.47, 95% CI = 0.28-0.81, P = 0.006; and adjusted OR = 
      0.51, 95% CI = 0.26-0.99, P = 0.048, respectively) compared with those having a 
      -579TT genotype. The -283T allele was linked with the -579G allele, and haplotype 
      -283T/-579G was associated with a significantly decreased risk of AC (adjusted OR 
      = 0.48, 95% CI = 0.29-0.81, P = 0.006) as compared with haplotype -283C/-579T. In 
      a promoter assay, carriage of the -283T allele showed a significantly lower 
      promoter activity ( approximately 50%) compared with the -283C allele (P < 
      0.001), but the -579G > T polymorphism did not have an affect on the DNMT3B 
      promoter activity. These results suggest that the DNMT3B -283T > C polymorphism 
      influences DNMT3B expression, thus contributing to the genetic susceptibility to 
      lung cancer.
FAU - Lee, Su Jeong
AU  - Lee SJ
AD  - Cancer Research Institute, Kyungpook National University Hospital, Samduk 2Ga 50, 
      Daegu, 700-412, Korea.
FAU - Jeon, Hyo-Sung
AU  - Jeon HS
FAU - Jang, Jin-Sung
AU  - Jang JS
FAU - Park, Sun Ha
AU  - Park SH
FAU - Lee, Ga Young
AU  - Lee GY
FAU - Lee, Byung-Heon
AU  - Lee BH
FAU - Kim, Chang Ho
AU  - Kim CH
FAU - Kang, Young Mo
AU  - Kang YM
FAU - Lee, Won Kee
AU  - Lee WK
FAU - Kam, Sin
AU  - Kam S
FAU - Park, Rang Woon
AU  - Park RW
FAU - Kim, In-San
AU  - Kim IS
FAU - Cho, Young Lae
AU  - Cho YL
FAU - Jung, Tae Hoon
AU  - Jung TH
FAU - Park, Jae Yong
AU  - Park JY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041104
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
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  - DNA Methylation
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Haplotypes/genetics
MH  - Humans
MH  - Korea
MH  - Lung Neoplasms/*genetics
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - *Promoter Regions, Genetic
MH  - Smoking/adverse effects
MH  - DNA Methyltransferase 3B
EDAT- 2004/11/06 09:00
MHDA- 2005/03/11 09:00
CRDT- 2004/11/06 09:00
PHST- 2004/11/06 09:00 [pubmed]
PHST- 2005/03/11 09:00 [medline]
PHST- 2004/11/06 09:00 [entrez]
AID - bgh307 [pii]
AID - 10.1093/carcin/bgh307 [doi]
PST - ppublish
SO  - Carcinogenesis. 2005 Feb;26(2):403-9. doi: 10.1093/carcin/bgh307. Epub 2004 Nov 
      4.