title: Functional repeats (TGYCC)n in the p53-inducible gene 3 (PIG3) promoter and susceptibility to squamous cell carcinoma of the head and neck.
abstract: A polymorphic pentanucleotide microsatellite sequence (TGYCC)n within the p53-inducible gene 3 (PIG3) promoter is correlated with the extent of transcriptional activation by p53 and thought to modulate susceptibility to cancer. Using a PCR-silver staining-based single-strand conformation assay, we visualized variant genotypes of the PIG3 promoter (TGYCC)n motif in a subset of 100 subjects for each of four ethnic groups: non-Hispanic whites, African Americans, Hispanic Americans and Native Chinese. We found that PIG3 (TGYCC)15 was the most common allele but less frequent in non-Hispanic whites (0.660) than in Chinese (0.785) (P = 0.016). In an additional study of 616 patients with squamous cell carcinoma of the head and neck (SCCHN) and 623 cancer-free controls in a non-Hispanic white population, we found that compared with those who were PIG3 (TGYCC)15 homozygotes, subjects without the PIG3 (TGYCC)15 allele had a significantly increased SCCHN risk [adjusted odds ratio (OR) = 1.34; 95% CI = 1.04-1.73 for heterozygotes and OR = 1.69; 95% CI = 1.18-2.44 for variant homozygotes] in an allele-dose response manner (P = 0.002). Consistently, subsequent luciferase reporter assay revealed that the wild-type (TGYCC)15 allele had the highest p53-mediated transcriptional activity, compared with the other (TGYCC)n motifs. Our data suggest that the PIG3 variant polymorphic repeats alleles other than (TGYCC)15 may affect p53 binding and thus may be a marker for susceptibility to SCCHN, but our findings need to be validated in larger studies.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Guan
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Luo
authors.initials: L
authors.lastname: Wang
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D001741:Black or African American / Q000235:genetics; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology*; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck; D015533:Transcriptional Activation; D044465:White People / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; C411296:TP53I3 protein, human