(ChemotherapyAdvisor) – What role do psychosocial factors play in cancer progression? That was the question-generating hypothesis that led investigators to determine that in patients with renal cell carcinoma (RCC), depressive symptoms are a key predictor of survival, “with potential links to dysregulation of cortisol and inflammatory biology,” they concluded in the journal PLoS ONE online August 1, 2012.

“Our findings provide the first evidence that levels of depressive symptoms are associated with survival time among patients with newly diagnosed advanced RCC, controlling for disease-and treatment-related factors,” noted Lorenzo Cohen, PhD, and colleagues from The University of Texas MD Anderson Cancer Center, Houston, TX.

They prospectively enrolled 217 patients with metastatic RCC. Each provided blood and saliva samples and completed several questionnaires, including the Centers for Epidemiologic Studies – Depression (CES-D), SF-36 Health Status Survey, Duke Social Support Index, Coping Operations Preference Enquiry, organized and non-organized religious activity, and intrinsic religiosity. The investigators assessed cortisol levels and whole genome transcriptional profiling to identify potential alterations in circadian rhythms and genomic pathways.

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After controlling for disease risk category in Cox regression models, CES-D scores (HR 1.5 [95% CI, 1.00–2.23]; P=0.05) and cortisol slope (HR 1.9 [95%CI 1.27–2.97]; P=0.002) were found to be significantly associated with decreased survival. In the complete model, “only cortisol slope and risk category remained significant,” Dr.Cohen reported.

A link between depressive symptoms and increased expression of pro-inflammatory and pro-metastatic genes in circulating leukocytes was identified using functional genomic analyses. In patients with high CES-D scores, 116 transcripts were found to be upregulated by an average of ≥50% and 57 transcripts downregulated by at least 50%, changes also were found in the tumor in a subset of patients.

The study “also found an association between a blunting of normal diurnal variation in cortisol levels to increased risk of mortality,” they wrote.

“Although previous research has shown that depression and cortisol slope are associated with survival in cancer patients, this study provides new evidence that those two dynamics might be related, and that altered cortisol regulation might partially mediate the relationship between depressive symptoms and cancer progression.”