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A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer.

Publication ,  Journal Article
Shen, H; Wang, L; Spitz, MR; Hong, WK; Mao, L; Wei, Q
Published in: Cancer Res
September 1, 2002

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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

September 1, 2002

Volume

62

Issue

17

Start / End Page

4992 / 4995

Location

United States

Related Subject Headings

  • Smoking
  • Risk Factors
  • Promoter Regions, Genetic
  • Polymorphism, Genetic
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Logistic Models
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Shen, H., Wang, L., Spitz, M. R., Hong, W. K., Mao, L., & Wei, Q. (2002). A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer. Cancer Res, 62(17), 4992–4995.
Shen, Hongbing, Luo Wang, Margaret R. Spitz, Waun K. Hong, Li Mao, and Qingyi Wei. “A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer.Cancer Res 62, no. 17 (September 1, 2002): 4992–95.
Shen H, Wang L, Spitz MR, Hong WK, Mao L, Wei Q. A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer. Cancer Res. 2002 Sep 1;62(17):4992–5.
Shen, Hongbing, et al. “A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer.Cancer Res, vol. 62, no. 17, Sept. 2002, pp. 4992–95.
Shen H, Wang L, Spitz MR, Hong WK, Mao L, Wei Q. A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer. Cancer Res. 2002 Sep 1;62(17):4992–4995.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

September 1, 2002

Volume

62

Issue

17

Start / End Page

4992 / 4995

Location

United States

Related Subject Headings

  • Smoking
  • Risk Factors
  • Promoter Regions, Genetic
  • Polymorphism, Genetic
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Logistic Models
  • Humans