Journal Article

<i>DNMT3B</i> 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 and Jae Yong Park

in Carcinogenesis

Volume 26, issue 2, pages 403-409
Published in print February 2005 | ISSN: 0143-3334
Published online February 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh307
DNMT3B polymorphisms and risk of primary lung cancer

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  • Clinical Cytogenetics and Molecular Genetics

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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.

Keywords: AC, adenocarcinoma; CI, confidence interval; DNMT, DNA methyltransferase; OR, odds ratio; SCC, squamous cell carcinoma; SM, small cell carcinoma; SNP, single nucleotide polymorphism; SP1, simian virus-40 protein 1

Journal Article.  5681 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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