Abstract 154: Lifetime ovulatory cycles and risk of ovarian and endometrial cancers.
Authors: Yang Hannah P. , Murphy Kelsey , George Neena , Garcia-Closas Montserrat , Lissowska Jolanta , Brinton Louise A. , Wentzensen Nicolas 
Published: August 2014

Background: Incessant ovulation is a widely accepted hypothesis for ovarian carcinogenesis. “Lifetime ovulatory cycles” (LOC) is considered a composite variable that combines events that suppress ovulation in a woman's menstrual span. Due to the lack of direct measurements for incessant ovulation periods, epidemiological studies have used models to calculate LOC. Although several epidemiologic studies have tested the hypothesis that high LOC increases the risk of ovarian cancer, there has been little attention focused on relationships with other gynecological cancers, such as endometrial cancer.

Objectives: (1) Identify existing LOC algorithms through a systematic literature review. (2) Apply each algorithm to assess the association between LOC and ovarian and endometrial cancer risks in a population-based case-control study with detailed reproductive variables.

Methods: We conducted a systematic review of PubMed to June 2012 using the following search terms: “lifetime ovulatory cycles, ovulatory cycles and cancer," and “incessant ovulation”. Algorithms identified were then used to calculate the LOC for participants in the Polish Ovarian and Endometrial Cancer Studies. For each algorithm (quartiles of LOC among controls), odds ratio (OR) and 95% confidence intervals were calculated for ovarian and endometrial using unconditional logistic regression, adjusted for cancer-specific potential confounders.

Results: We identified 17 studies including 18 unique LOC algorithms based on different combinations of the following variables: age at menopause, age at menarche, oral contraceptive use duration, breastfeeding duration, time pregnant, number and outcome of each pregnancy, average menstrual cycle length, and postpartum or other periods of amenorrhea. We limited the analysis of the LOC definitions (n=12) based on the availability of the variables in the Polish Study. Our analysis was based on 315 ovarian cancer cases/1,951 associated controls and 540 endometrial cancer cases and 1,895 associated controls, after exclusions. A core set of variables used to calculate LOC, including age at menopause/menarche, oral contraceptive use, and duration of breast feeding yielded similar associations with cancer risk compared to more complex models. In comparing the highest to the lowest LOC quartile using the various algorithms, women were at increased risk of ovarian (OR range 1.90 ∼3.48) and endometrial cancer risk (OR range 2.02 ∼ 2.95) with the confidence limits overlapping. Conclusions: LOC models differed in the use of relevant variables and in their complexity, however increased numbers of LOC were associated with increased risk of ovarian and endometrial cancers across all algorithms in our study. These data suggests that LOC algorithms might be formulated based on a core set of variables that are widely available variables in epidemiological studies.

Citation Format: Hannah P. Yang, Kelsey Murphy, Neena George, Montserrat Garcia-Closas, Jolanta Lissowska, Louise A. Brinton, Nicolas Wentzensen. Lifetime ovulatory cycles and risk of ovarian and endometrial cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 154. doi:10.1158/1538-7445.AM2013-154