Carcinogenesis Advance Access originally published online on August 11, 2007
Carcinogenesis 2007 28(9):2008-2012; doi:10.1093/carcin/bgm172
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
1 Department of Epidemiology
2 Department of Head and Neck Surgery
3 Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
4 Present address: Department of Epidemiology and Biostatistics, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, China
* To whom correspondence should be addessed. Tel: +1 713 792 3020; Fax: +1 713 563 0999; Email: qwei{at}mdanderson.org
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.
Abbreviations: BAX, B-cell lymphoma 2-associated X protein; BCL2, B-cell lymphoma 2; CI, confidence interval; LOH, loss of heterozygosity; OR, odds ratio; PCR, polymerase chain reaction; SCCHN, squamous cell carcinoma of the head and neck; SNP, single-nucleotide polymorphism; TP53, tumor protein 53
Received April 20, 2007; revised June 12, 2007; accepted July 20, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Song, H. Zheng, B. Liu, S. Wei, H. Dai, L. Zhang, G. A. Calin, X. Hao, Q. Wei, W. Zhang, et al. An miR-502-Binding Site Single-Nucleotide Polymorphism in the 3'-Untranslated Region of the SET8 Gene Is Associated with Early Age of Breast Cancer Onset Clin. Cancer Res., October 1, 2009; 15(19): 6292 - 6300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Lehnerdt, P. Franz, A. Bankfalvi, S. Grehl, A. Kelava, H. Nuckel, S. Lang, K. W. Schmid, W. Siffert, and H. S. Bachmann The regulatory BCL2 promoter polymorphism (-938C>A) is associated with relapse and survival of patients with oropharyngeal squamous cell carcinoma Ann. Onc., June 1, 2009; 20(6): 1094 - 1099. [Abstract] [Full Text] [PDF]
|
|