Does Pregnancy Induce the Shedding of Premalignant Ovarian Cells?

Background. High parity is associated with reduced risk of ovarian cancer. One hypothesis is that pregnancy is associated with clearance of a fraction of the genetically modified (pre-malignant) cells from the ovaries. Methods. We evaluated this hypothesis using a model that estimates the cell clearance fraction at first and second pregnancy according to age at pregnancy. The model was fitted using reproductive history data from a cohort of 1.5 million Danish women born between 1935 and 1978 and followed for 28.7 million person-years. During this follow-up period, 2,035 developed invasive ovarian cancer. Results. We found the model to have a satisfactory fit despite the very few parameters involved. The model estimated similar cell clearance fractions for the first and second pregnancy and decreasing clearance with later age at pregnancy. Conclusion. The relation of pregnancy history to risk of ovarian cancer can be well described by a cell clearance model that allows the cell clearance fraction to decrease with age at pregnancy.