Gender of Offspring and Maternal Risk of Invasive Epithelial Ovarian Cancer

Abstract

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 casecontrol 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. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2314 -20)

Reproductive characteristics in relation to ovarian cancer risk by histologic pathways

“…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.…”

What is new about ovarian malignancies?

“…The biological explanations for this phenomenon might be associated with different maternal hormone concentrations [13]. Despite the fact that the study failed to reach statistical significance, previous studies -in eastern Pennsylvania [14] and Sweden [15] -reported similar findings. Slightly different results were reported in a recent pooled analysis among participants from 12 case-control studies, which included 6872 EOC patients.…”

Offspring sex and risk of epithelial ovarian cancer: a multinational pooled analysis of 12 case–control studies

“…A earlier population-based study of 511 cases and 1136 controls conducted in eastern Pennsylvania, USA from 1994-1998 by the same group reported similar findings -relative to all female offspring, bearing all male offspring was associated with decreased EOC risk (OR=0.80)(26). These findings were supported by a nested case-control study within the population-based Swedish Fertility Register that included 7,407 women diagnosed with EOC between 1961 and 2001 and 37,658 controls( 27): compared to bearing all female offspring, bearing a male child was associated with reduced EOC risk in a dose-response fashion (ORs: 0.92, 0.87, 0.82, for 1, 2 or 3+ boys, compared to all girls) (27). In contrast, the Australia-wide population-based study (AUS) conducted between 2002 and 2005 and included in this pooled analysis reported no association between offspring sex and EOC for parous women in general but a 2-fold increased risk of the mucinous histotype associated with bearing only male offspring (29).…”

“…Few epidemiologic studies have explored the relationship between offspring sex and EOC, and results have been inconsistent (26)(27)(28)(29)(30). Methodological limitations including small sample sizes overall and for specific histotypes may account for these disparate findings.…”