Abstract A45: The association between type 2 diabetes mellitus and incidence of renal cell carcinoma (RCC) and fatal RCC in two prospective cohorts
Authors: Graff Rebecca E. , Sanchez Alejandro , Cheng Jed-Sian , Rodriguez Dayron , Feldman Adam S. , Barrisford Glen , Bechis Seth , Blute Michael L. , Stampfer Meir , Preston Mark A. , Wilson Kathryn M. , Cho Eunyoung 
Published: October 2015

Abstract
Introduction: Current epidemiologic evidence suggests that type 2 diabetes (T2D) is associated with an increased risk of renal cell carcinoma (RCC), but no prospective studies have explored the association in both men and women. Postulated mechanisms include hyperinsulinemia, increases in circulating growth factors, increased endogenous estrogens, and changes in glucose availability. Given the increasing incidence of T2D it is imperative to further evaluate its role in RCC incidence.
Methods: We investigated the association between T2D and RCC using prospective cohorts of 117,616 women from the Nurses' Health Study (NHS) and 48,818 men from the Health Professionals Follow-up Study. Self-reports of physician-diagnosed diabetes were collected at baseline, updated biennially, and confirmed via supplemental questionnaires. We used multivariable Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of both total and fatal pathology-confirmed RCC. Models were adjusted for BMI, hypertension, smoking, alcohol intake, NSAID use, and physical activity. Additional adjustment for race, fruit, and vegetable intake did not affect results.
Results: During 34 years of follow-up in the NHS we confirmed 309 cases of RCC, including 60 fatal cases. During 24 years of follow-up in the HPFS we confirmed 214 total cases, including 34 fatal cases. In women, T2D was associated with a significantly increased risk of incident RCC (multivariable HR 1.55; 95%CI 1.08 – 2.19), but not fatal RCC (multivariable HR 0.74; 95%CI 0.22 – 2.48). In men, T2D was not associated with an increased risk of incident RCC (multivariable HR 1.10; 95%CI 0.65 – 1.86), but men with T2D were at a non-significantly higher risk of fatal RCC (multivariable HR 2.89; 95%CI 0.93 – 9.02). Compared to non-diabetic women, the association between T2D and RCC was non-significantly stronger in women with a shorter duration of T2D (multivariable HR for ≤ 5 years: HR 2.11; 95%CI 1.31 – 3.38; for &gt; 5 years: HR 1.23; 95%CI 0.77 – 1.95; pdiff: 0.58). In men, duration of T2D was not associated with an increased risk of incident RCC.
Conclusions: Our results support previous findings of an association between T2D and incidence of RCC in women; however, we found no significant association in men. T2D may be associated with an increased risk of fatal RCC in men, though power for this analysis in men and women was low.
Citation Format: Rebecca E. Graff, Alejandro Sanchez, Jed-Sian Cheng, Dayron Rodriguez, Adam S. Feldman, Glen Barrisford, Seth Bechis, Michael L. Blute, Meir Stampfer, Mark A. Preston, Kathryn M. Wilson, Eunyoung Cho. The association between type 2 diabetes mellitus and incidence of renal cell carcinoma (RCC) and fatal RCC in two prospective cohorts. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A45.