p53 and WAF1 polymorphisms in Jewish-Israeli women with epithelial ovarian cancer and its association with BRCA mutations

BJOG. 2000 Jul;107(7):849-54. doi: 10.1111/j.1471-0528.2000.tb11082.x.

Abstract

Objective: To investigate whether polymorphic p53 and WAF1 alleles are associated with clinical, demographic and histopathological features and BRCA mutation in women with ovarian cancer.

Design: A cross-sectional study.

Population: Two hundred and twenty-one nonselected Israeli women with epithelial ovarian cancer.

Methods: DNA was analysed for known polymorphisms in intron 3 (a 16 nucleotide single repeat) and intron 6 (a G to A change at nucleotide 13,494) of the p53 gene, the S31R polymorphism in the WAF1 gene, and for three predominant Jewish mutations in the BRCA genes (185delAG and 5382insC in BRCA1, and 6174delT in BRCA2).

Main outcome measure: The rate of polymorphic p53 and WAF1 alleles and their association with BRCA mutation, ethnic origin, age and stage at diagnosis, and family history of cancer.

Results: Of the tested women, 72 (32.6%) were either BRCA1 (n = 57) or BRCA2 (n = 15) mutation carriers. Sixty-eight of 213 (31.9%) were heterozygous for intron 3 polymorphism, 67/193 (34.7%) for intron 6 polymorphism, and 22/154 (14.3%) for S31R of the WAF1 gene. The p53 and WAF1 polymorphism rate did not differ between BRCA mutation carriers and noncarriers. No significant association between specific p53 or WAF1 genotypes, and clinical, histopathological or demographic variables was observed.

Conclusion: In Jewish-Israeli women with sporadic and familial ovarian cancer, p53 or WAF1 polymorphisms do not seem to affect the phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BRCA2 Protein
  • Cross-Sectional Studies
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics*
  • Female
  • Genes, BRCA1 / genetics*
  • Genes, p53 / genetics*
  • Genotype
  • Humans
  • Israel / ethnology
  • Jews / genetics
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms / genetics*
  • Polymorphism, Genetic*
  • Risk Factors
  • Transcription Factors / genetics

Substances

  • BRCA2 Protein
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Neoplasm Proteins
  • Transcription Factors