Elsevier

Gynecologic Oncology

Volume 72, Issue 2, February 1999, Pages 187-192
Gynecologic Oncology

Regular Article
WAF1 Genotype and Endometrial Cancer Susceptibility

https://doi.org/10.1006/gyno.1998.5247Get rights and content

Abstract

The WAF1 protein, which is a downstream mediator of p53, functions as a universal inhibitor of cyclin-dependent kinases. The functional link between p53 and WAF1 suggests the possibility that alteration in WAF1 function constitutes an alternative mechanism to p53 inactivation. However, there are few reports describing somatic mutations of the WAF1 gene in various human malignancies. A polymorphism in the WAF1 gene, a C-to-A transversion at codon 31 resulting in the change of a serine (Ser) to an arginine (Arg), is well known. We found this substitution in 42 of 54 endometrial carcinoma patients. Allele frequency was 0.44/0.56 for the codon 31 polymorphism (Ser/Arg), the difference of allele frequency between patients and normal controls being significant (0.59/0.41 in normal controls). In addition, individuals carrying the codon 31 Arg allele had a tendency to develop histologically high-grade (odds ratio, 6.11) and clinically advanced tumors. We investigated the association of the Arg allele with the known risk factors of endometrial carcinomas. Statistical analyses of 42 cases and 32 controls carrying the codon 31 Arg allele identified hypertension (odds ratio, 4.33) and family history of cancer (odds ratio, 2.81) as positive risk factors. This implies that these two parameters may be associated with a tendency to develop endometrial carcinomas in individuals carrying the codon 31 Arg allele of the WAF1 gene.

References (33)

  • AJ Levine et al.

    The p53 tumour suppressor gene

    Nature

    (1991)
  • M Hollstein et al.

    p53 mutations in human cancers

    Science

    (1991)
  • Yonish-Raouach, E, Resnitzky, D, Lotem, J, Sachs, L, Kimchi, A, Oren, M, Wild-type p53 induces apoptosis of myeloid...
  • JW Harper et al.

    The p21 Cdk-Interacting Cip1 is a potent inhibitor of G1 cyclin-dependent kinases

    Cell

    (1993)
  • Y Xion et al.

    p21 is a universal inhibitor of cyclin kinases

    Nature

    (1993)
  • X Gao et al.

    Somatic mutations of the WAF1/CIP1 gene in primary prostate cancer

    Oncogene

    (1995)
  • Cited by (30)

    View all citing articles on Scopus
    1

    To whom correspondence and reprint requests should be addressed. Fax: 81-977-27-1661.

    View full text