Analysis of CDKN1A polymorphisms: Markers of cancer susceptibility?

  • Rodrigues F
  • Kawasaki-Oyama R
  • Fo J
 et al. 
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Abstract

The CDKN1A (TP21) gene encodes a 21-kD protein that is a critical downstream mediator of wild-type TP53 and an important regulator of the cell cycle. Failure in the function of this gene would be expected to result in abnormal cell proliferation and transformation. Tumor-associated mutations of the coding region of the TP21 are rare. On the other hand, some TP21 polymorphisms have been identified and characterized by single base substitutions. In the present study, we investigated the potential role of TP21 gene polymorphisms in skin, head, and neck tumorigenesis. A total of 261 samples were examined by polymerase chain reaction single-strand conformational analysis, and one mutation at codon 31 and four polymorphisms in exons 2 (codon 55) and 3 [nucleotide (nt)590] and in promoter region (nt2298) were identified. In conclusion, this investigation confirmed the rarity of mutations in this gene, arguing against a role for TP21 mutations in skin, head, and neck cancers. Also, our results show significant differences in nt2298 allele frequencies between normal individuals and skin malignant tumors (P < 0.05). The results suggest that this polymorphism affects TP21 transactivator binding and may be important during the pathogenesis of skin cancer. © 2003 Elsevier Science Inc. All rights reserved.

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Authors

  • Flávia C.C. Rodrigues

  • Rosa S. Kawasaki-Oyama

  • José F.Gois Fo

  • Érica E. Ukuyama

  • João Roberto Antonio

  • Antonio R. Bozola

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