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A novel functional variant (-842G>C) in the PIN1 promoter contributes to decreased risk of squamous cell carcinoma of the head and neck by diminishing the promoter activity.

Publication ,  Journal Article
Lu, J; Hu, Z; Wei, S; Wang, L-E; Liu, Z; El-Naggar, AK; Sturgis, EM; Wei, Q
Published in: Carcinogenesis
October 2009

PIN1, a new peptidyl-prolyl cis/trans isomerase, regulates the conformation of Pro-directed phosphorylation sites, revealing a new postphosphorylation regulatory mechanism. PIN1-induced conformational changes potentiate multiple oncogenic signaling pathways, and PIN1 overexpression is reported as a prevalent and specific event in human cancers. In this study, we tested the hypothesis that common polymorphisms in the coding and promoter regions of PIN1 are associated with risk of squamous cell carcinoma of the head and neck (SCCHN). We genotyped three selected PIN1 polymorphisms (-842G>C, -667T>C and Gln33Gln) in a hospital-based case-control study of 1006 patients with SCCHN and 1007 cancer-free control subjects. We found that the -842C variant genotypes were associated with decreased risk for SCCHN [Odds Ratio (OR) = 0.74; 95% confidence interval (CI) = 0.59-0.93 for the CG genotype, OR = 0.82; 95% CI = 0.34-2.01 for the CC genotype and OR = 0.74; 95% CI = 0.59-0.93 for CG+CC genotypes, compared with the GG genotype]. However, no altered risks were observed for -667T>C and Gln33Gln polymorphisms. Further experiments of the reporter gene expression driven by the allelic PIN1 promoter showed that the -842G allele had a higher activity than that driven by the -842C allele, suggesting that the -842C allele was associated with a reduced transcriptional activity, a finding consistent with a reduced risk observed in the case-control analysis. Large prospective studies of diverse ethnic groups and diverse cancer sites are warranted to validate our findings.

Duke Scholars

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

October 2009

Volume

30

Issue

10

Start / End Page

1717 / 1721

Location

England

Related Subject Headings

  • Risk Assessment
  • Reference Values
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Polymorphism, Genetic
  • Plasmids
  • Peptidylprolyl Isomerase
  • Oncology & Carcinogenesis
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Mutagenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lu, J., Hu, Z., Wei, S., Wang, L.-E., Liu, Z., El-Naggar, A. K., … Wei, Q. (2009). A novel functional variant (-842G>C) in the PIN1 promoter contributes to decreased risk of squamous cell carcinoma of the head and neck by diminishing the promoter activity. Carcinogenesis, 30(10), 1717–1721. https://doi.org/10.1093/carcin/bgp171
Lu, Jiachun, Zhibin Hu, Sheng Wei, Li-E Wang, Zhensheng Liu, Adel K. El-Naggar, Erich M. Sturgis, and Qingyi Wei. “A novel functional variant (-842G>C) in the PIN1 promoter contributes to decreased risk of squamous cell carcinoma of the head and neck by diminishing the promoter activity.Carcinogenesis 30, no. 10 (October 2009): 1717–21. https://doi.org/10.1093/carcin/bgp171.
Lu, Jiachun, et al. “A novel functional variant (-842G>C) in the PIN1 promoter contributes to decreased risk of squamous cell carcinoma of the head and neck by diminishing the promoter activity.Carcinogenesis, vol. 30, no. 10, Oct. 2009, pp. 1717–21. Pubmed, doi:10.1093/carcin/bgp171.

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

October 2009

Volume

30

Issue

10

Start / End Page

1717 / 1721

Location

England

Related Subject Headings

  • Risk Assessment
  • Reference Values
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Polymorphism, Genetic
  • Plasmids
  • Peptidylprolyl Isomerase
  • Oncology & Carcinogenesis
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Mutagenesis