High serum TGFα, TNFα and IL6 correlate with abnormal circadian rhythms in patients with metastatic colorectal cancer (MCC)

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9650 Background: Poor quality of life and poor survival of cancer patients were independently predicted by an alteration of the rest-activity (RA) and/or cortisol circadian rhythms. This disturbance could be mediated by high levels of tumor- or host- derived growth factors, known to modulate circadian clock function.Methods: TGFα, TNFα and IL6 levels were determined with ELISA in sera from 80 MCC patients whose rhythms in RA (wrist actimetry for 3 d) and cortisol (serum drawn at 08:00 and 16:00 ) were prospectively studied (Mormont et al. Clin Cancer Res 2000). The samples were selected from patients having rhythmic (group 1, n=40) or damped (group 2, n=40) RA pattern, as assessed with autocorrelation for a period of 24 h (r24). Groups were compared with Kruskall-Wallis test. Correlations between factor concentrations and circadian parameters were explored with Spearman ρ test.Results: Median RA r24 were 0.56 (range, 0.47 to 0.77) in group 1 and 0.22 (0.03 to 0.35) in group 2 (p < 0.0001). Median cortisol ratio (value at 08:00 / value at 16:00 ± quartile) were 1.72 [1.48 - 1.98] and 1.60 [1.14 - 1.77] respectively (p = 0.031). Median (± quartile) dichotomy index (I<O), an integrated estimate of RA pattern and sleep quality, was 98.5 % [97.0 - 99.7] in group 1 and 91.4 % [82.1 - 96.7] in group 2 (p < 0.0001). TGFα, TNFα and IL6 serum levels (pg/ml) were significantly lower in group 1 as compared to group 2 (Table) and negatively correlated with I<O (r = - 0.45, p < 0.0001; r = -0.27, p = 0.022; r = -0.37, p = 0.001, respectively). IL6 levels were also negatively correlated with cortisol rhythm estimate (r = - 0.31, p = 0.005). Conclusions: Altered circadian function was associated with increased production of cancer-derived growth factors, suggesting a mechanism through which a tumor can promote its own development via the disturbance of host physiology. Supported by: ARTBC; J W Sieg fund. No significant financial relationships to disclose.