Carcinogenesis Advance Access published online on August 11, 2007
Carcinogenesis, doi:10.1093/carcin/bgm172
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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
1 Department of Epidemiology, and The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
2 Department of Head and Neck Surgery and The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
3 Department of Pathology, and The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
** To whom correspondence should be addressed: Qingyi Wei, Department of Epidemiology, Unit 1365, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. Tel: 713-792-3020; Fax: 713-563-0999; Email: qwei{at}mdanderson.org
TP53, a transcriptional factor, induces expression of the BAX gene by directly binding to the TP53-binding element in the BAX promoter but inhibits 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 analysis, 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 [OR=6.60, 95% 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 and OR=0.67, 95% CI=0.48-0.95 for AA, respectively) compared with the BCL2 CC genotype. 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 in SCCHN, particularly among TP53 heterozygotes. Larger studies are needed to validate these findings.
Key Words: Case-control study • Apoptosis • Genetic susceptibility • Molecular epidemiology • Polymorphism
* Current address: Department of Epidemiology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
Received April 20, 2007; revised June 12, 2007; accepted July 20, 2007.
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