Gender of Offspring and Maternal Risk of Invasive Epithelial Ovarian Cancer

Harvard University, Cambridge, Massachusetts, United States
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 11/2007; 16(11):2314-20. DOI: 10.1158/1055-9965.EPI-07-0645
Source: PubMed


Gender of a fetus is associated with maternal hormonal milieu and may therefore modify maternal risk of ovarian cancer following a birth. We evaluated the relation between gender of offspring and maternal risk of epithelial ovarian cancer in a large case-control study nested within a nationwide cohort. Cohort members were identified in the Swedish Fertility Register. Cases of invasive epithelial ovarian cancer were identified in the Swedish National Cancer Register from 1961 to 2001. Five controls were matched by age to each case. A total of 7,407 cases and 37,658 controls with only singleton births were included in the analysis. We fit logistic regression models to study the association between gender of offspring and ovarian cancer risk, controlling for covariates. Maternal risk of ovarian cancer was reduced with increasing numbers of male offspring and increased with number of female offspring. Compared with women who gave birth to only girls, multivariate odds ratios (95% confidence interval) of invasive epithelial ovarian cancer were 0.92 (0.87-0.98) for those who gave birth to one boy, 0.87 (0.80-0.94) for two boys, and 0.82 (0.73-0.94) for three or more boys (P value test for trend <0.001). There was a positive but nonsignificant association with number of girls. Similar results were observed when restricting the analysis to women born before 1935. Our findings suggest that hormonal and physiologic conditions in pregnancy with male, but not with female, offspring are associated with a lowered maternal risk of invasive epithelial ovarian cancer.

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Available from: Anders Ekbom, Oct 05, 2015
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    • "The protection conferred by pregnancy has been attributed to various mechanisms including anovulation (Fathalla, 1971 ), reduced gonadotrophin secretion (Cramer and Welch, 1983 ) and higher levels of progesterone (Risch, 1998). However, we hypothesize that the strong protective effect for the first pregnancy, particularly for type II/highgrade serous and clear cell tumors, is consistent with the mechanism where pregnancy may clear away cells that have accumulated somatic mutations over time and/or have already undergone malignant transformation (Adami et al., 1994), possibly acting through hormonal changes that occur during pregnancy such as increased levels of progesterone, which may induce apoptosis (Risch, 1998; Rodriguez et al., 1998; Lambe et al., 1999; Riman et al., 2004; Lukanova and Kaaks, 2005; Baik et al., 2007). In contrast, each subsequent pregnancy would be expected to induce a similar cell clearance; however, the cell population remaining after the first pregnancy would have comparatively less time to accumulate mutations. "
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    ABSTRACT: STUDY QUESTION: Do reproductive risk factor associations differ across subgroups of invasive epithelial ovarian cancer (EOC) defined by the dualistic model (type I/II) or a histologic pathway-based classification? SUMMARY ANSWER: Associations with parity, history of endometriosis, tubal ligation and hysterectomy were found to differ in the context of the type I/II and the histologic pathways classification of ovarian cancer. WHAT IS KNOWN ALREADY: Shared molecular alterations and candidate precursor lesions suggest that tumor histology and grade may be used to classify ovarian tumors into likely etiologic pathways. DESIGN: This case-control study included 1571 women diagnosed with invasive EOC and 2100 population-based controls that were enrolled from 1992 to 2008. Reproductive risk factors as well as other putative risk factors for ovarian cancer were assessed through in-person interviews. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible cases were diagnosed with incident ovarian cancer, were aged 18 and above and resided in eastern Massachusetts or New Hampshire, USA. Controls were identified through random digit dialing, drivers' license and town resident lists and were frequency matched with the cases based on age and study center. MAIN RESULTS AND THE ROLE OF CHANCE: We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for type I/II EOC or using a pathway-based grouping of histologic subtypes. In multivariate analyses, we observed that having a history of endometriosis (OR = 1.92, 95% CI: 1.36-2.71) increased the risk for a type I tumor. Factors that were strongly inversely associated with risk for a type I tumor included parity (≥3 versus 0 children, OR = 0.15, 95% CI: 0.11-0.21), having a previous tubal ligation (OR = 0.40, 95% CI: 0.26-0.60) and more weakly hysterectomy (OR = 0.71, 95% CI: 0.45-1.13). In analyses of histologic pathways, parity (≥3 versus 0 children, OR = 0.13, 95% CI: 0.10-0.18) and having a previous tubal ligation (OR = 0.41, 95% CI: 0.28-0.60) or hysterectomy (OR = 0.54, 95% CI: 0.34-0.86) were inversely associated with risk of endometrioid/clear cell tumors. Having a history of endometriosis strongly increased the risk for endometrioid/clear cell tumors (OR = 2.41, 95% CI: 1.78-3.26). We did not observe significant differences in the risk associations across these tumor classifications for age at menarche, menstrual cycle length or infertility. LIMITATIONS, REASONS FOR CAUTION: A potential limitation of this study is that dividing the cases into subgroups may limit the power of these analyses, particularly for the less common tumor types. Since cases were enrolled after their diagnosis, it is possible that the most aggressive cases were not included in the study. WIDER IMPLICATIONS OF THE FINDINGS: This study provides insights about the role of reproductive factors in relation to risk of pathway-based subgroups of ovarian cancer that with further confirmation may assist with the development of improved strategies for the prevention of these different tumor types. STUDY FUNDING/COMPETING INTEREST(S): This research is funded by grants from the National Cancer Institute, the Department of Defense Ovarian Cancer Research Program and the Ovarian Cancer Research Fund. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.
    Preview · Article · Jan 2013 · Human Reproduction
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    • "Strengths of our study include the population-based nature of the study, the large sample size, and histologically verified cases. With the large number of subjects, analyses of data from this study have been able to identify the postpartum period when the risk of maternal ovarian cancer is at its lowest [18] and examine the effect of offspring gender on the risk of maternal ovarian cancer [29]. There are potential limitations. "
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    ABSTRACT: Pregnancies reduce the risk of ovarian cancer, and among multiparous women, levels of circulating progesterone might be higher during pregnancies with wider birth spacing. We hypothesized that childbirth with wider birth spacing might reduce maternal risk of invasive epithelial ovarian cancer more than births with narrower spacing. We conducted a case-control study nested in a nationwide cohort of Swedish women from 1961 to 2001. We selected five individually age-matched controls for each case of invasive epithelial ovarian cancer, and analysis for the effect of birth spacing was performed for 5,341 cases and 29,047 controls. We applied unconditional logistic regression analyses adjusting for age, ages at childbirth, educational level, area of residence, and gender of offspring. Relative risk of invasive epithelial ovarian cancer associated with each one-year increase in average birth spacing is 1.00 (95% CI = 0.98-1.01) among all women and 0.99 (0.98-1.01) among those born before 1935 and less likely to have used oral contraceptives. Further analyses on the biparous and triparous women did not find a consistent association between birth spacing and the risk of ovarian cancer. Birth spacing is unlikely to be a major determinant underlying the protective effects of childbirth on ovarian cancer risk.
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    ABSTRACT: Ovarian cancer in the adolescent and young adult (AYA) population is a disease that is distinctly different with regard to risk factors, genetics, and pathology when compared to ovarian cancers occurring in older women. This article will review the theories behind ovarian carcinogenesis and attempt to elucidate why these tumors exhibit their unique biologic characteristics. Knowledge of these differences will allow us to begin to develop strategies for future research endeavors enabling improved survival in AYA women diagnosed with ovarian cancer.
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