Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-9-28
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2008-12
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17693666-Carcinoma, Squamous Cell, pubmed-meshheading:17693666-Case-Control Studies, pubmed-meshheading:17693666-Female, pubmed-meshheading:17693666-Genotype, pubmed-meshheading:17693666-Head and Neck Neoplasms, pubmed-meshheading:17693666-Humans, pubmed-meshheading:17693666-Male, pubmed-meshheading:17693666-Middle Aged, pubmed-meshheading:17693666-Polymerase Chain Reaction, pubmed-meshheading:17693666-Polymorphism, Single Nucleotide, pubmed-meshheading:17693666-Promoter Regions, Genetic, pubmed-meshheading:17693666-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:17693666-Reference Values, pubmed-meshheading:17693666-Risk Factors, pubmed-meshheading:17693666-Texas, pubmed-meshheading:17693666-Tumor Suppressor Protein p53, pubmed-meshheading:17693666-bcl-2-Associated X Protein
pubmed:year
2007
pubmed:articleTitle
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.
pubmed:affiliation
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural