Individual differences in pre-carcinogen cytokine and corticosterone concentrations and depressive-like behavior predict tumor onset in rats exposed to a carcinogen

Abstract

Individual variation in the susceptibility to chronic disease can be attributed to both genetic and environmental factors. Measures of the immune, nervous, and endocrine systems are predictive of survival outcomes after a chronic disease is diagnosed. However, determining biomarkers or "traits" that predict risk before chronic disease development remains elusive. In this study, natural individual variation in circulating cytokines, corticosterone, and depressive-like behaviors (using the Porsolt forced swim test) were measured in female rats before induction of mammary tumors using a chemical carcinogen (N-nitroso-N-methylurea). Early tumor onset was associated with relatively high (but within the physiologically typical range) circulating cytokine concentrations (IL-1α, IL-1β, TNFα) and depressive-like behavior and with relatively low corticosterone concentrations, all of which were assessed at baseline before carcinogen treatment. Multiple regression analyses indicated that IL-1β was primarily responsible for the variation in tumor onset when controlling for corticosterone concentration. These results suggest that the susceptibility to tumor initiation and/or growth may be related to individual differences in baseline immune and endocrine physiology and emotional tone present at the time of carcinogen exposure. Investigation of the mechanistic relevance of these individual differences may lead to prophylactic approaches to cancer treatment in the context of carcinogen exposure.