Abstract:
: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.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Lee SJ,Jeon HS,Jang JS,Park SH,Lee GY,Lee BH,Kim CH,Kang YM,Lee WK,Kam S,Park RW,Kim IS,Cho YL,Jung TH,Park JYdoi
10.1093/carcin/bgh307keywords:
subject
Has Abstractpub_date
2005-02-01 00:00:00pages
403-9issue
2eissn
0143-3334issn
1460-2180pii
bgh307journal_volume
26pub_type
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