Relationship between colorectal cancer glutathione levels and patient survival: early results.

Abstract

Elevated glutathione is a cause of resistance to anticancer agents and x-rays. The purpose of this study was to determine the frequency and clinical significance of glutathione elevation in human colorectal cancer. Glutathione levels were measured in 41 colon cancers, 24 rectal cancers, and corresponding normal tissues. The patients were then followed up prospectively for tumor recurrence and survival. Survival was analyzed by the Kaplan-Meir method and Cox proportional hazards regression. Glutathione levels in primary colorectal cancers were significantly higher than in the corresponding normal tissues. Elevated glutathione levels had a significant negative effect on survival in patients with colorectal cancer, whether based on the mean (P = 0.02) or median (P = 0.04) normal tissue levels. A negative effect of glutathione levels on survival was apparent in patients with colorectal cancer, whether or not they were treated with postoperative therapy. The larger the ratio of tumor glutathione to normal tissue glutathione, the poorer the prognosis. When adjusted for other covariates, glutathione was still a significant predictor of survival. An elevated tumor glutathione level at the time of diagnosis appears to confer a poor prognosis in patients with colorectal cancer. Longer-term study using a larger number of patients will be required to confirm these findings. Knowledge of tumor glutathione content may help identify patients requiring more intensive therapy.