Multiple miscarriages are associated with the risk of ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition.
Braem MGM., Onland-Moret NC., Schouten LJ., Kruitwagen RFPM., Lukanova A., Allen NE., Wark PA., Tjønneland A., Hansen L., Braüner CM., Overvad K., Clavel-Chapelon F., Chabbert-Buffet N., Teucher B., Floegel A., Boeing H., Trichopoulou A., Adarakis G., Plada M., Rinaldi S., Fedirko V., Romieu I., Pala V., Galasso R., Sacerdote C., Palli D., Tumino R., Bueno-de-Mesquita HB., Gram IT., Gavrilyuk O., Lund E., Sánchez M-J., Bonet C., Chirlaque M-D., Larrañaga N., Gurrea AB., Quirós JR., Idahl A., Ohlson N., Lundin E., Jirström K., Butt S., Tsilidis KK., Khaw K-T., Wareham N., Riboli E., Kaaks R., Peeters PHM.
While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR(≥4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR(≥4vs.0): 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR(≥4vs.0): 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.