title: p53 pathway gene single nucleotide polymorphisms and chronic lymphocytic leukemia.
abstract: The p53 pathway plays a critical role in chronic lymphocytic leukemia (CLL). The association between the single-nucleotide polymorphism (SNPs) within the p53 gene (R72P) and its downstream target/regulators, BAX (G125A) and MDM2 (SNP309), and clinical parameters/prognostic markers was investigated in 83 CLL patients. Although the p53 R72P SNPs and MDM2 SNP309 did not associate with any of the parameters studied, the BAX G125A SNPs was associated with a more advanced Binet stage at diagnosis, supporting a potential role for this variant in CLL disease progression. In reporter assays, however, the BAX 5' untranslated region G125A SNPs surprisingly caused a 1.8-fold increase in basal promoter activity and did not alter the ability of p53 to trans-activate the promoter. Further studies are required to understand the role of SNPs in the p53 pathway in CLL.
authors.affiliation: Cancer Research UK Clinical Centre, University of Southampton School of Medicine, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Onoshua
authors.initials: O
authors.lastname: Lahiri
authors.forename: Scott
authors.initials: S
authors.lastname: Harris
authors.forename: Graham
authors.initials: G
authors.lastname: Packham
authors.forename: Melanie
authors.initials: M
authors.lastname: Howell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494826:BAX protein, human; D005819:Genetic Markers; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2