title: Glutathione S-transferase pi in colorectal tumors is predictive for overall survival.
abstract: Glutathione S-transferases (GSTs) are enzymes involved in the detoxification of xenobiotics and are divided into four subclasses, alpha, mu, pi, and theta, with different although overlapping substrate specificities. Most human gastrointestinal tumors contain increased amounts of GST-pi and GST enzyme activity. The relationship between GST parameters and tumor and patient characteristics, including overall survival, were studied retrospectively in 100 primary colorectal adenocarcinomas. Levels of GST-alpha, GST-mu, GST-pi, and GST enzyme activity were not related to the Dukes stage, differentiation grade, localization, histological type and diameter of the tumor, or gender and age of the patient. Fifty-seven patients died (median survival, 21 months; range, 1-65 months) during follow-up, and 43 patients were still alive at the closing date of the study (median follow-up, 68 months; range, 60-87 months). Optimal dichotomization and uni- and multivariate analyses were done with the Cox proportional hazard model. Multivariate analysis with all clinicopathological parameters revealed higher Dukes stage (hazard ratio, 2.7; P < 0.001) and older age (hazard ratio, 2.8; P = 0.001) to be the only independent prognostic variables for overall survival. In contrast to GST-alpha and GST-mu, high levels of GST-pi (hazard ratio, 3.1; P = 0.002) and GST enzyme activity (hazard ratio, 2.0; P = 0.020) in the tumors were found to have a significant prognostic value independent from the clinicopathological parameters when added separately to this Cox model. Thus, this study indicates that GST subclass levels in colorectal adenocarcinomas are not related to clinicopathological parameters and that the GST-pi level and GST enzyme activity have a prognostic value for the overall survival of the patients.
authors.affiliation: Department of Gastroenterology, St. Radboud University Hospital, Nijmegen, The Netherlands.
authors.forename: T P
authors.initials: TP
authors.lastname: Mulder
authors.forename: H W
authors.initials: HW
authors.lastname: Verspaget
authors.forename: C F
authors.initials: CF
authors.lastname: Sier
authors.forename: H M
authors.initials: HM
authors.lastname: Roelofs
authors.forename: S
authors.initials: S
authors.lastname: Ganesh
authors.forename: G
authors.initials: G
authors.lastname: Griffioen
authors.forename: W H
authors.initials: WH
authors.lastname: Peters
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005982:Glutathione Transferase / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D012727:Sex Characteristics; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D005982:Glutathione Transferase