DNMT3B polymorphisms and risk of primary lung cancer

Su Jeong Lee, Hyo Sung Jeon, Jin Sung Jang, Sun Ha Park, Ga Young Lee, Byung Heon Lee, Chang Ho Kim, Young Mo Kang, Won Kee Lee, Sin Kam, Rang Woon Park, In-San Kim, Young Lae Cho, Tae Hoon Jung, Jae Yong Park

Research output: Contribution to journalArticle

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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 (∼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.

Original languageEnglish
Pages (from-to)403-409
Number of pages7
JournalCarcinogenesis
Volume26
Issue number2
DOIs
Publication statusPublished - 2005 Feb 1
Externally publishedYes

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Lung Neoplasms
Alleles
Odds Ratio
Haplotypes
Confidence Intervals
Adenocarcinoma
Transcription Initiation Site
Genotype
Exons
Small Cell Carcinoma
DNA methyltransferase 3B
DNA Methylation
Genetic Predisposition to Disease
Methylation
Carcinogenesis
Population
Genes

ASJC Scopus subject areas

  • Cancer Research

Cite this

Lee, S. J., Jeon, H. S., Jang, J. S., Park, S. H., Lee, G. Y., Lee, B. H., ... Park, J. Y. (2005). DNMT3B polymorphisms and risk of primary lung cancer. Carcinogenesis, 26(2), 403-409. https://doi.org/10.1093/carcin/bgh307

DNMT3B polymorphisms and risk of primary lung cancer. / Lee, Su Jeong; Jeon, Hyo Sung; Jang, Jin Sung; Park, Sun Ha; Lee, Ga Young; Lee, Byung Heon; Kim, Chang Ho; Kang, Young Mo; Lee, Won Kee; Kam, Sin; Park, Rang Woon; Kim, In-San; Cho, Young Lae; Jung, Tae Hoon; Park, Jae Yong.

In: Carcinogenesis, Vol. 26, No. 2, 01.02.2005, p. 403-409.

Research output: Contribution to journalArticle

Lee, SJ, Jeon, HS, Jang, JS, Park, SH, Lee, GY, Lee, BH, Kim, CH, Kang, YM, Lee, WK, Kam, S, Park, RW, Kim, I-S, Cho, YL, Jung, TH & Park, JY 2005, 'DNMT3B polymorphisms and risk of primary lung cancer', Carcinogenesis, vol. 26, no. 2, pp. 403-409. https://doi.org/10.1093/carcin/bgh307
Lee SJ, Jeon HS, Jang JS, Park SH, Lee GY, Lee BH et al. DNMT3B polymorphisms and risk of primary lung cancer. Carcinogenesis. 2005 Feb 1;26(2):403-409. https://doi.org/10.1093/carcin/bgh307
Lee, Su Jeong ; Jeon, Hyo Sung ; Jang, Jin Sung ; Park, Sun Ha ; Lee, Ga Young ; Lee, Byung Heon ; Kim, Chang Ho ; Kang, Young Mo ; Lee, Won Kee ; Kam, Sin ; Park, Rang Woon ; Kim, In-San ; Cho, Young Lae ; Jung, Tae Hoon ; Park, Jae Yong. / DNMT3B polymorphisms and risk of primary lung cancer. In: Carcinogenesis. 2005 ; Vol. 26, No. 2. pp. 403-409.
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