Abstract B25: Kidney cancer and female reproductive factors in two prospective cohorts
Authors: Karami Sara , Daugherty Sarah E. , Park Yikyung , Hollenbeck Albert R. , Purdue Mark P. 
Published: June 2012

Introduction: The unexplained two-fold lower incidence of kidney cancer in women compared to men and findings from clinical and experimental studies have generated interest in the role of female reproductive factors and exogenous hormones on kidney cancer development. Endocrine system involvement in kidney cancer development is biologically plausible since sex hormone receptors have been detected in normal and malignant renal tissue, exogenous estrogens have been shown to promote and induce kidney cancer formation, and anatomic changes to the kidney during pregnancy may make nephrons more vulnerable to inflammation and oxidative stress. Findings from several epidemiologic studies suggest that parity may be associated with kidney cancer, but case numbers have generally been small. Associations with other reproductive factors have been sparse and inconsistently reported. Therefore, we conducted a pooled analysis of two large prospective studies to evaluate whether hormone-related factors are associated with risk of kidney cancer in women.

Methods: We investigated the relationship between female reproductive factors and exogenous hormones and kidney cancer risk in two large prospective cohort studies: the NIH-AARP Diet and Health Study (NIH-AARP: 601 cases) and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO: 191 cases). Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression. Data from both studies were pooled and aggregate HRs were estimated. We also conducted meta-analyses of all case-control and cohort studies to summarize our new findings and previously reported associations between kidney cancer risk and select reproductive factors. Random-effects models were fit to estimate summary relative risks (RRs) and odds ratios (ORs) for cohort and case-control studies separately.

Results: The analysis included 283,952 post-menopausal women, with 792 incident kidney cancer cases. Parity was not associated with risk of kidney cancer in either study (pooled HR = 1.15, 95% Cl = 0.91–1.44). Risk for kidney cancer was significantly elevated, however, in both cohorts among women who had undergone a hysterectomy (pooled HR = 1.33,95% Cl = 1.15–1.53). After allowing for a 10 year lag between study baseline and diagnosis of kidney cancer, associations remained significantly elevated (pooled HR = 1.31,95% Cl = 1.14–1.51), suggesting the elevation in association was not due to detection bias. For women with a history of endometriosis, a significant increase in risk (HR = 1.69,95% Cl = 1.09–2.62) was observed in PLCO, the only cohort that collected data on this condition.

A meta-analysis of epidemiologic studies provided additional support for an association with hysterectomy (all cohort studies: summary RR = 1.29,95% Cl = 1.14–1.47; excluding NIH-AARP and PLCO Results: summary RR = 1.23,95% Cl = 0.99–1.52; case-control studies: OR = 1.39,95% Cl = 1.17–1.64).

Conclusion: Our findings from two large prospective cohorts and a meta-analysis of epidemiologic studies suggests that hysterectomy is associated with increased kidney cancer risk.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B25.