Functional repeats (TGYCC)n in the p53-inducible gene 3 (PIG3) promoter and susceptibility to squamous cell carcinoma of the head and neck.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Guan, X; Liu, Z; Wang, L; Wang, L-E; Sturgis, EM; Wei, Q

Published Date

  • April 2013

Published In

Volume / Issue

  • 34 / 4

Start / End Page

  • 812 - 817

PubMed ID

  • 23241165

Pubmed Central ID

  • 23241165

Electronic International Standard Serial Number (EISSN)

  • 1460-2180

International Standard Serial Number (ISSN)

  • 0143-3334

Digital Object Identifier (DOI)

  • 10.1093/carcin/bgs388

Language

  • eng