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

Objective To investigate whether polymorphic p53 and WAF1 alleles are assoc iated with clinical, demographic and histopathological features and BRCA mu tation in women with ovarian cancer. Design Across-sectional study. Population Two hundred and twenty-one nonselected Israeli women with epithe lial ovarian cancer. Methods DNA was analysed for known polymorphisms in intron 3 (a 16 nucleoti de single repeat) and intron 6 (a G to A change at nucleotide 13,494) of th e p53 gene, the S31R polymorphism in the WAF1 gene, and for three predomina nt 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 f or 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 d id not differ between BRCA mutation carriers and noncarriers. No significan t association between specific p53 or WAF1 genotypes, and clinical, histopa thological or demographic variables was observed. Conclusion In Jewish-Israeli women with sporadic and familial ovarian cance r, p53 or WAF1 polymorphisms do not seem to affect the phenotype.