Abstract B18: Prediagnostic physical inactivity and epithelial ovarian cancer risk and mortality: Evidence from the Ovarian Cancer Association Consortium.

Abstract

Abstract Despite a growing number of studies evaluating associations between physical activity and epithelial ovarian cancer risk and mortality, the extant evidence is inconclusive, both for epithelial ovarian cancer (EOC) overall, and by individual histotypes. The inconsistency of epidemiological findings may be due to some apparent limitations in the literature. First, individual studies of EOC often have relatively small numbers of case subjects, especially for less common histotypes. Second, physical activity is a complex behavior involving several characteristics that have been measured differently by the various self-report questionnaires utilized among epidemiological studies. Third, many studies in the existing literature have utilized referent groups combining women who report no regular physical activity with women who report some physical activity, which could obscure the relationship between physical activity and EOC risk or mortality, if one exists. Objective: We conducted a pooled analysis of individual-level data from 12 studies from the Ovarian Cancer Association Consortium to investigate the association between recreational physical inactivity and EOC risk and mortality. Methods: In accordance with the 2008 Physical Activity Guidelines for Americans, women were classified as inactive, our exposure of interest, if they reported participating in recreational physical activities less than once per week, on average, throughout adulthood. To decrease the likelihood of reverse causation as an explanation for observed associations, studies using activity data from the reference date only were excluded in sensitivity analyses. For risk assessment, case data were from 9,024 women aged 18 years and older with a primary diagnosis of borderline or invasive EOC including serous, mucinous, endometrioid or clear cell tumors. Control data were from 13,643 women aged 18 years and older who had at least partially intact ovaries and no histories of ovarian cancer. We employed both meta-analytic and combined individual-data approaches to evaluate the associations between physical inactivity and EOC risk. For mortality outcomes, follow-up data and vital status were available for 6,807 cases. Using a combined dataset, multivariable Cox proportional hazards regression analyses were utilized to generate Hazard Ratios (HRs) and 95% CIs for the association between physical inactivity and all-cause mortality. We also examined risks of EOC-specific mortality and disease progression in a smaller subset of patients with available follow-up data. Results: In risk analyses, we observed a significant positive association between recreational physical inactivity and risk of EOC (OR=1.39, 95% CI: 1.18-1.63, p<0.001). Significant risk elevations ranging between 30% to 55% among inactive women were also observed across the individual EOC histotypes. In survival analyses, there were 3,899 all-cause deaths for analysis. We observed a significant increased multivariable adjusted risk of death among inactive women in comparison to more active women (HR=1.14, 95% CI: 1.06-1.23, p<0.001). We also observed increased risk of EOC-specific mortality, but the association did not achieve statistical significance (HR=1.10, 95% CI: 0.95-1.28, p=0.211). Lastly, we observed a significantly higher risk of disease progression among inactive patients (HR=1.22, 95% CI: 1.09-1.37, p=0.001). Conclusions: These data suggest that recreational physical inactivity in adulthood is associated with an increased risk of EOC. Our data also supports an association between inactivity with risk of disease progression and mortality. These associations were robust to adjustment for relevant confounders and to sensitivity analyses designed to decrease the likelihood of reverse causation as an explanation for observed associations. Given the growing prevalence of inactivity in the U.S. and worldwide, these findings are relevant to public health and cancer prevention and control. Citation Format: Rikki A. Cannioto, Michael LaMonte, Ovarian Cancer Association Consortium (OCAC), Kirsten B. Moysich. Prediagnostic physical inactivity and epithelial ovarian cancer risk and mortality: Evidence from the Ovarian Cancer Association Consortium. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B18.