Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition.
Tsilidis KK., Allen NE., Key TJ., Dossus L., Lukanova A., Bakken K., Lund E., Fournier A., Overvad K., Hansen L., Tjønneland A., Fedirko V., Rinaldi S., Romieu I., Clavel-Chapelon F., Engel P., Kaaks R., Schütze M., Steffen A., Bamia C., Trichopoulou A., Zylis D., Masala G., Pala V., Galasso R., Tumino R., Sacerdote C., Bueno-de-Mesquita HB., van Duijnhoven FJB., Braem MGM., Onland-Moret NC., Gram IT., Rodríguez L., Travier N., Sánchez M-J., Huerta JM., Ardanaz E., Larrañaga N., Jirström K., Manjer J., Idahl A., Ohlson N., Khaw K-T., Wareham N., Mouw T., Norat T., Riboli E.
BACKGROUND: It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear. METHODS: We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327,396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use. RESULTS: Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41-0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59-0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ≤ 45 years: HR, 1.46; 95% CI, 1.06-1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk. CONCLUSION: This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors.