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Single-nucleotide polymorphisms at the TP53-binding or responsive promoter regions of BAX and BCL2 genes and risk of squamous cell carcinoma of the head and neck.

Publication ,  Journal Article
Chen, K; Hu, Z; Wang, L-E; Sturgis, EM; El-Naggar, AK; Zhang, W; Wei, Q
Published in: Carcinogenesis
September 2007

Tumor protein 53 (TP53), a transcriptional factor, induces expression of the B-cell lymphoma 2-associated X protein (BAX) gene by directly binding to the TP53-binding element in the BAX promoter but inhibits B-cell lymphoma 2 (BCL2) promoter-driven transcription through a responsive region in the BCL2 promoter. Therefore, we hypothesized that single-nucleotide polymorphisms (SNPs) of BAX and BCL2 promoters and the TP53 codon 72 SNP may jointly contribute to cancer risk. We tested this hypothesis in a hospital-based case-control study of 814 patients with squamous cell carcinoma of the head and neck (SCCHN) and 934 cancer-free controls in a US non-Hispanic white population. While there was no evidence of associations between BAX (-248 G>A), BCL2 (-938 C>A) or TP53 codon 72 SNPs and SCCHN risk in single-locus analyses, further analyses showed that, among TP53 heterozygotes after adjustment for age, sex and smoking and alcohol status, the BAX AA genotype was associated with an elevated risk of SCCHN [odds ratio (OR) = 6.60, 95% confidence interval (CI) = 1.38-31.50 compared with the BAX GG genotype or OR = 6.58, 95% CI = 1.38-31.49 compared with the combined genotypes (GG + AG)], whereas BCL2 A variant genotypes were associated with a decreased risk of SCCHN (adjusted OR = 0.68, 95% CI = 0.47-0.98 for CA vs CC and OR = 0.67, 95% CI = 0.48-0.95 for AA vs CA+CC). These altered risks appeared to be consistent with the roles of the anti-apoptotic BCL2 and the pro-apoptotic BAX. Our data suggest that the risk of SCCHN may be associated with these two SNPs of BAX and BCL2 promoter regions, particularly among TP53 heterozygotes. Larger studies are needed to validate these findings.

Duke Scholars

Published In

Carcinogenesis

DOI

ISSN

0143-3334

Publication Date

September 2007

Volume

28

Issue

9

Start / End Page

2008 / 2012

Location

England

Related Subject Headings

  • bcl-2-Associated X Protein
  • Tumor Suppressor Protein p53
  • Texas
  • Risk Factors
  • Reference Values
  • Proto-Oncogene Proteins c-bcl-2
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, K., Hu, Z., Wang, L.-E., Sturgis, E. M., El-Naggar, A. K., Zhang, W., & Wei, Q. (2007). Single-nucleotide polymorphisms at the TP53-binding or responsive promoter regions of BAX and BCL2 genes and risk of squamous cell carcinoma of the head and neck. Carcinogenesis, 28(9), 2008–2012. https://doi.org/10.1093/carcin/bgm172
Chen, Kexin, Zhibin Hu, Li-E Wang, Erich M. Sturgis, Adel K. El-Naggar, Wei Zhang, and Qingyi Wei. “Single-nucleotide polymorphisms at the TP53-binding or responsive promoter regions of BAX and BCL2 genes and risk of squamous cell carcinoma of the head and neck.Carcinogenesis 28, no. 9 (September 2007): 2008–12. https://doi.org/10.1093/carcin/bgm172.
Chen K, Hu Z, Wang L-E, Sturgis EM, El-Naggar AK, Zhang W, et al. Single-nucleotide polymorphisms at the TP53-binding or responsive promoter regions of BAX and BCL2 genes and risk of squamous cell carcinoma of the head and neck. Carcinogenesis. 2007 Sep;28(9):2008–12.
Chen, Kexin, et al. “Single-nucleotide polymorphisms at the TP53-binding or responsive promoter regions of BAX and BCL2 genes and risk of squamous cell carcinoma of the head and neck.Carcinogenesis, vol. 28, no. 9, Sept. 2007, pp. 2008–12. Pubmed, doi:10.1093/carcin/bgm172.
Chen K, Hu Z, Wang L-E, Sturgis EM, El-Naggar AK, Zhang W, Wei Q. Single-nucleotide polymorphisms at the TP53-binding or responsive promoter regions of BAX and BCL2 genes and risk of squamous cell carcinoma of the head and neck. Carcinogenesis. 2007 Sep;28(9):2008–2012.
Journal cover image

Published In

Carcinogenesis

DOI

ISSN

0143-3334

Publication Date

September 2007

Volume

28

Issue

9

Start / End Page

2008 / 2012

Location

England

Related Subject Headings

  • bcl-2-Associated X Protein
  • Tumor Suppressor Protein p53
  • Texas
  • Risk Factors
  • Reference Values
  • Proto-Oncogene Proteins c-bcl-2
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis