Epithelial Ovarian Carcinoma and Fertility of Parents

To the Editor: In a case-control study of 163 women with epithelial ovarian cancer and 159 controls from New York City, Harlap et al. 1 found an inverse relation between number of siblings and ovarian cancer, with a 20% risk reduction per additional sibling. They suggested that heritable conditions associated with parents’ reduced fertility may be an indicator of risk. We were able to consider such a hypothesis on the basis of a large case-control study conducted between 1992 and 1999 in six areas of Italy. 2 Briefly, cases were 1031 women with incident, histologically confirmed epithelial ovarian cancer, and controls were 2441 women admitted to hospital for acute, nonneoplastic conditions (26% traumas, 28% nontraumatic orthopedic conditions, 15% acute surgical conditions, and 31% other miscellaneous diseases). Fewer than 4% of cases and controls approached refused the interview. Trained interviewers questioned cases and controls in the hospital, using a structured questionnaire that included information on personal characteristics and habits, education and other socioeconomic factors, general lifestyle habits, diet, hormonal and reproductive history, and personal and family history of selected medical conditions. The subjects were specifically asked how many sisters and brothers they had. 3 We estimated the odds ratios (OR) of ovarian cancer according to the number of siblings, using unconditional multiple logistic regression models that included terms for age, study center, geographic area, education, parity, oral contraceptive use, personal history of infertility, and family history of ovarian and breast cancer in first-degree relatives. Table 1 gives the distribution of cases and controls according to the number of siblings. Compared with women who had no siblings, the ORs were 1.1 for those with one sibling, 1.3 for two siblings, 1.1 for three siblings, and 1.0 for four or more siblings. The OR for each additional sibling was 0.98 (95% confidence interval [CI] = 0.94–1.01), and corresponding values for each sister and brother were 0.97 (0.92–1.02) and 0.98 (0.92–1.04), respectively.TABLE 1: Distribution of 1031 Ovarian Cancer Cases and 2411 Controls According to Number of Siblings and Corresponding Odds Ratios, Italy 1992–1999Our study, which included an unusually large number of ovarian cancer cases, did not support the hypothesis that number of siblings, as a measure of the fertility of subjects’ parents, affects ovarian cancer risk. These findings are unlikely to be attributable to bias because the response rate was virtually complete, information bias on the number of siblings is unlikely, and allowance was made in the analysis for major identified potential confounding factors. Furthermore, our results concerning menstrual and reproductive factors are consistent with current knowledge of the issue 4; the risk of ovarian cancer was, in fact, inversely related to parity, late age at menarche, early menopause, and longer oral contraceptive use. 2 Cristina Bosetti Eva Negri Silvia Franceschi Renato Talamini Carlo La Vecchia