Relationship between colorectal cancer glutathione levels and patient survival - Early results

PURPOSE: Elevated glutathione is a cause of resistance to anticancer agents and x-rays. The purpose of this study was to determine the frequency and c linical significance of glutathione elevation in human colorectal cancer. M ETHODS: Glutathione levels were measured in 41 colon cancers, 24 rectal can cers, and corresponding normal tissues. The patients were then followed up prospectively for tumor recurrence and survival. Survival was analyzed by t he Kaplan-Meir method and Cox proportional hazards regression. RESULTS: Glu tathione levels in primary colorectal cancers were significantly higher tha n in the corresponding: normal tissues. Elevated glutathione levels had a s ignificant negative effect on survival in patients with colorectal cancer, whether based on the mean (P = 0.02) or median (P = 0.04) normal tissue lev els. A negative effect of glutathione: levels on survival was apparent in p atients with colorectal cancer, whether or not they were treated with posto perative therapy. The larger the ratio of tumor glutathione to normal tissu e glutathione, the poc,rer the prognosis. When adjusted fur other covariate s, glutathione was still a significant predictor of survival. CONCLUSIONS: An elevated tumor glutathione level at the time of diagnosis appears to con fer a poor prognosis in patients with colorectal cancer. Longer-term study using a larger number of patients will he required to confirm these finding s, Knowledge of tumor glutathione content may help identify patients requir ing more intensive therapy.