BERKELEY, CA (UroToday.com) - Obesity is an established and diabetes mellitus (DM) a possible risk factor for renal cell carcinoma (RCC).[1] Moreover, hormones produced in adipose tissue might be involved in complex pathways of homeostasis, inflammation, and immunity, a hypothesis that has attracted investigators to explore their potential role in carcinogenesis. In this context, we previously investigated the association of adiponectin[2] and leptin[3] with RCC risk, whereas in this study we aim to explore whether insulin resistance (IR) plays an independent role in the development of RCC.
In a hospital-based, case-control study, we analyzed serum glucose, insulin, leptin, and adiponectin levels among 60 incident RCC patients and 236 age- and gender-matched healthy controls. We assessed IR according to insulin levels, alone or controlled for DM. An alternative measure of IR, notably the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index, was also assessed with and without controlling for history of DM. We used logistic regression to estimate odds ratios (ORs) adjusted for possible confounders.
The positive association of DM and waist-to-hip ratio as a measure of central obesity with RCC was also evident in this study. Insulin levels, controlled or not controlled for DM, however, were inversely associated with the risk for RCC; notably, an approximately 40% higher risk was observed in the first tertile when compared with the second and third tertile levels of insulin resistance. Similar results were obtained when HOMA-IR was alternatively used. The inverse associations persisted, and were even strengthened, after controlling for potential confounding factors in multivariate analyses.
Our data suggest that insulin resistance may be inversely associated with RCC risk, independently of obesity, DM, leptin, adiponectin, and lifestyle confounding variables. Complex interactions and cross talking might play a role, given the response of some RCC cases to immunotherapeutic agents and the immune properties of leptin. The possible methodological limitations due to study design are highlighted along with the efforts made to reduce systematic bias. Strengths of our study include high participation rates among eligible case patients and control subjects, as well as strictly standardized procedures for personal interview, blood sampling, and laboratory analyses. The number of participants was small but allowed us to refute the null hypothesis. Our most fundamental concern is selection bias among controls. Because population-based sampling was not feasible, we used a secondary source, namely individuals attending health screening procedures. We cannot provide proof that their exposure prevalence adequately reflects the person-time that generated our cases.
As a corollary, our study should be considered hypothesis-generating for a malignancy with a poorly understood pathophysiology. Inherent limitations of our study design were the lack of the time sequence criterion for causality, and the fact that no measurement of insulin growth factors (IGFs) or other insulin-resistance associated hormones and metabolites or their receptors were available. Despite its limitations, to our knowledge, this is the first study that investigated the association of insulin resistance with RCC risk. If confirmed in independent, well-designed studies, our findings may generate etiologic hypotheses and perhaps even be relevant for the management of patients suffering from RCC or its specific subtypes.
References:
- Cho E, Adami HO, Lindblad P. Epidemiology of Renal Cell Cancer. Hematol Oncol Clin N Am 2011;25:651-665.
- Spyridopoulos TN, Petridou ET, Skalkidou A, et al., 2007 Adiponectin levels are associated with renal carcinoma: A case-control study. Int J Cancer 120:1573-1578.
- Spyridopoulos TN, Petridou ET, Dessypris N, et al., 2009 Inverse association of leptin levels with renal cell carcinoma: results from a case-control study. Hormones (Athens) 8:39-46.
Written by:
Themistoklis N. Spyridopoulos,a Hans-Olov Adami,b, c George P. Chrousos,d and Eleni Th. Petridou,a as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
aDepartment of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School
bDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
cDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
d1st Department of Pediatrics, Athens University Medical School, Athens, Greece
Insulin resistance and risk of renal cell cancer: A case-control study - Abstract
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