Diurnal cortisol rhythm as a predictor of lung cancer survival.
BACKGROUND: Poorly coordinated diurnal cortisol and circadian rest-activity rhythms predict earlier mortality in metastatic breast and colorectal cancer, respectively. We examined the prognostic value of the diurnal cortisol rhythm in lung cancer. METHODS: Lung cancer patients (n=62, 34 female) were within 5 years of diagnosis and had primarily non small-cell lung cancer, with disease stage ranging from early to advanced. Saliva collected over two days allowed calculation of the diurnal cortisol slope and the cortisol awakening response (CAR). Lymphocyte numbers and subsets were measured by flow cytometry. Survival data were obtained for 57 patients. Cox Proportional Hazards analyses were used to test the prognostic value of the diurnal cortisol rhythm on survival calculated both from study entry and from initial diagnosis. RESULTS: The diurnal cortisol slope predicted subsequent survival over three years. Early mortality occurred among patients with higher slopes, or relatively "flat" rhythms indicating lack of normal diurnal variation (Cox Proportional Hazards p=.009). Cortisol slope also predicted survival time from initial diagnosis (p=.012). Flattened profiles were linked with male gender (t=2.04, df=59, p=.046) and low total and cytotoxic T cell lymphocyte counts (r=-.39 and -.30, p=.004 and .035, respectively). After adjustment for possible confounding factors, diurnal slope remained a significant, independent predictor of survival. CONCLUSIONS: Flattening of the diurnal cortisol rhythm predicts early lung cancer death. Data contribute to growing evidence that circadian disruption accelerates tumor progression.
Sephton, SE; Lush, E; Dedert, EA; Floyd, AR; Rebholz, WN; Dhabhar, FS; Spiegel, D; Salmon, P
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