Pm. Webb et al., RELATIONSHIP BETWEEN NUMBER OF OVULATORY CYCLES AND ACCUMULATION OF MUTANT P53 IN EPITHELIAL OVARIAN-CANCER, Journal of the National Cancer Institute, 90(22), 1998, pp. 1729-1734
Background: It has been suggested that increased numbers of ovulations
might increase the risk of p53 gene (also known as TP53) mutation in
the ovarian epithelium, thereby leading to the development of cancer.
The data supporting this hypothesis have come from an observation that
accumulation of p53 protein in epithelial ovarian cancer was strongly
associated with increasing numbers of ovulatory cycles. We have furth
er investigated the association between ovulatory history and p53 gene
mutation by use of data from a large case-control study of ovarian ca
ncer in Australia. Methods: Tissue blocks were available for immunohis
tochemical analysis of p53 protein from 234 case subjects, aged 18-79
years, who had invasive epithelial ovarian cancer. Epidemiologic data
were also available for these women and for 855 control subjects. Case
-case comparisons were made by use of prevalence ratios and 95% confid
ence intervals (CIs), and case-control comparisons were made by use of
odds ratios (ORs) and 95% CIs. All statistical tests were two-sided.
Results: There was no association between p53 accumulation and years o
f ovulation, Women with p53-positive cancers had undergone an average
of 29.3 years of ovulation compared with 29.0 years of ovulation for w
omen with p53-negative cancers (P = .8). Although the overall risk of
ovarian cancer development was significantly increased in women who ha
d undergone more years of ovulation (OR = 2.17; 95% CI = 1.543.05-for
greater than or equal to 35 years versus < 23 years of ovulation), the
re was no difference in the risk associated with p53-positive and p53-
negative cancers. Conclusions: These results confirm the association b
etween increased ovulation and ovarian cancer risk but do not support
the hypothesis that this association is due to an increased risk of p5
3 mutation with a greater number of ovulatory cycles.