Abstract POSTER-CTRL-1212: The impact of social isolation on ovarian cancer risk and survival
Authors: Poole Elizabeth M. , Kubzansky Laura , Okereke Olivia I. , Tworoger Shelley S. 
Published: August 2015

Abstract
Introduction: In ovarian cancer mouse models, social isolation has been associated with increased circulating markers of angiogenesis, cell migration, and impaired immune response, as well as increasing tumor burden and aggressiveness. In ovarian cancer patients, social isolation has been associated with increased circulating levels of inflammatory and pro-angiogenic factors. However, social isolation has not been investigated in relation to ovarian cancer risk or survival in humans; we addressed these questions in the Nurses’ Health Study (NHS), a longitudinal cohort of 121,701 US-based nurses.
Methods: The Berkman-Syme social network index (BSSNI), a validated measure of social isolation, was assessed every four years in the NHS, starting in 1992. The BSSNI is based on marital status, close friends and relatives, as well as attendance at religious services and other group activities. Women were categorized into four groups: socially isolated, moderately isolated, moderately integrated, and socially integrated. We assessed risk of ovarian cancer associated with the BSSNI and its component parts using Cox proportional hazards models, adjusted for age, duration of oral contraceptive use, family history of ovarian cancer, parity, menopause status, duration of menopausal hormone therapy (by type), and tubal ligation. We further investigated whether the timing of social isolation impacted the results, by evaluating social isolation measured 0-4, 4-8, and 8-12 years prior to cancer diagnosis. In addition, we used Cox proportional hazards models to evaluate whether pre-diagnosis social isolation affected ovarian cancer survival, adjusting as described above plus stage and histology.
Results: In follow-up from 1992-2010, we identified 494 epithelial ovarian cancer cases among 53,839 women who completed the BSSNI. In our main analysis, socially isolated women had no increased ovarian cancer risk compared to socially integrated women (relative risk [RR]: 0.93; 95% confidence interval [CI]: 0.65-1.34), although case numbers were small (N=38). However, moderate isolation was associated with increased ovarian cancer risk (RR: 1.27; 95% CI: 1.00-1.61). When we assessed the components of the BSSNI, widowed women were at increased ovarian cancer risk (RR: 1.40; 95% CI: 1.12-1.75) compared to married women; none of the other BSSNI components were associated with ovarian cancer risk. In the analysis evaluating the role of timing of isolation, socially isolated women in the 8-12 years prior to diagnosis had increased ovarian cancer risk compared to socially integrated women (RR: 1.54; 95% CI: 1.02-2.33). Among the 494 ovarian cancer cases in this analysis, 313 women died due to ovarian cancer during follow-up. Neither the BSSNI nor its components were statistically significantly associated with ovarian cancer-specific survival; however, several of the associations were suggestive. For example, social isolation was not associated with survival (RR: 1.13; 95% CI: 0.41-3.13), but moderate isolation was suggestively associated (RR: 1.61; 95% CI: 0.87-3.00). Additionally, being widowed was associated with a 71% increased risk of ovarian cancer death (95% CI: 0.99-2.96).
Conclusion: These data add to a growing body of evidence that psychosocial stress is important for ovarian cancer risk and progression. Our data suggest that the timing of social isolation is key, which may have implications for the biology of stress. Future studies should confirm these results and evaluate additional sources of psychosocial stress.
Citation Format: Elizabeth M. Poole, Laura Kubzansky, Olivia I. Okereke, Shelley S. Tworoger. The impact of social isolation on ovarian cancer risk and survival [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-CTRL-1212.