Re: Relationship between lifetime ovulatory cycles and overexpression of mutant p53 in epithelial ovarian cancer.

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Abstract
Schildkraut et al. ( 1 ) recently reported an association between number of lifetime ovulatory cycles and the risk of p53-overexpressed invasive epithelial ovarian cancer, but not of p53-negative cancer. From the data they presented, I conclude exactly the opposite: p53-positive and p53-negative cancers are equally associated with ovulationrelated risk factors, the sole exception being age at diagnosis, which was on average some 3 years greater for the p53-positive case subjects. The study participants were all less than 55 years of age at diagnosis/interview; the majority were premenopausal or perimenopausal. Schildkraut et al. estimated the number of lifetime ovulatory cycles from a linear combination of five factors: age at most recent menstrual period (“index age”), age at menarche, and total durations of pregnancies, breastfeeding, and oral contraceptive use. None of the last four mentioned factors differed significantly between the p53-positive and p53-negative case subjects [ P = .71, .14, .06, and 0.23, respectively ( 1 )]. Comparing p53-positive and p53-negative cancers, the decreasing odds ratio trends with increasing months pregnant were very close ( 1 ), consistent in magnitude with the protective trends seen for parity in many other studies ( 2 , 3 ). Similarly, p53-positive and p53-negative cancers had virtually identical odds ratio trends with duration of oral contraceptive use ( 1 ), again of the same magnitude as seen elsewhere ( 2 , 3 ). Age at menarche and duration of breastfeeding contributed very little to the variation in number of ovulatory cycles ( 1 ). Thus, only index age is responsible for the purported difference in risk according to lifetime ovulatory cycles.