Abstract 868: The effects of age at term-births on risk of ovarian cancer

Abstract The large protective effect of number of births on the risk of ovarian cancer is well-established. Increasing parity is also associated with a large protective effect on the risk of endometrial cancer, and the effect is strongly dependent on the age at last birth. In a meta-analysis of data from four cohort and 13 case-control studies on endometrial cancer, Setiawan and colleagues found that after stratifying on number of births and adjusting for other risk factors including use of oral contraceptives, “women who last gave birth at 40 years of age or older had a 44% decreased risk compared to women who had their last birth under the age of 25 years” (Am J Epidemiol 2012; 176:269-278). Recent evidence suggests that the fallopian tube fimbria provides the cell of origin of the majority of ovarian cancer cases (high-grade serous ovarian cancers), and studies of cell proliferation in the fallopian tube show that it follows the same pattern in relation to the menstrual cycle as the endometrium. Endometriosis, which is strongly related to endometrioid and clear cell ovarian cancers, follows the same pattern of proliferative activity. These observations suggest that age at last birth may also play a role in the protective effect of births on ovarian cancer risk. We used the combined individual data from four population-based ovarian cancer case-control studies conducted in Los Angeles County over the period from 1993 to 2008. Cases were residents of Los Angeles County who had histologically confirmed invasive ovarian cancer. Neighborhood controls were women who had at least one intact ovary who had not been diagnosed with ovarian cancer at or before the date of interview. They were individually matched to patients on race/ethnicity as well as year of birth and recruited using a systematic well-established algorithm based on the addresses of the patients. All participants were interviewed in-person using a questionnaire that covered medical, reproductive, and personal lifestyle history. After adjusting for number of births, oral contraceptive use, and other factors, we observe a strong protective effect associated with a late age at last birth: a 13.0% (95% CI 5.6% - 19.8%) reduction in risk per five years later age. We also observed a strong protective effect of late age at first birth: a 17.5% (95% CI 9.9% - 24.5%) reduction per five years. The mutually adjusted reductions in risk per five years later were no longer statistically significant for age at last birth (4.3% (95% CI -8.0% - 13.5%)) but remained significant for age at first birth (15.4% (95% CI 4.6% - 25.0%)). Results contrary to our expectations. On preliminary analysis, we find no such timing effects for use of oral contraceptives. Given a timing effect of parity, it is unlikely that the mechanism underlying the protective benefit of births is simply blocking ovulation. These findings also underscore the differing effects of parity and oral contraceptives. These results have implications for both disease etiology as well as risk prediction modeling. Citation Format: Alice Lee, Celeste L. Pearce, Anna Wu, Malcolm Pike. The effects of age at term-births on risk of ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 868. doi:10.1158/1538-7445.AM2015-868