ABSTRACT
BACKGROUND: The purpose of this study was to evaluate the prognostic ability of polymorphisms of three genes involved in the metabolism of tobacco carcinogens (GSTT1, GSTM1, GSTP1) and one polymorphism of a DNA repair gene (XRCC1) for patients diagnosed with squamous cell carcinoma (SCC). METHODS: Cox proportional hazard models were used to estimate risk of death for a prospective cohort of 190 patients. RESULTS: Individuals with the GSTT1 functional genotype were twice as likely to die from any cause (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.13-4.97) and were three times as likely to die from SCC (HR, 3.4; 95% CI, 1.33-8.41) after adjustment for age, primary therapy, and stage of disease. The XRCC1 399 Gln genotype was predictive of disease recurrence. CONCLUSIONS: Our findings, from one of the first studies to examine this research question, suggest that genomic markers of carcinogen metabolism and DNA repair capability may serve as prognostic indicators of disease recurrence and death.
Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/mortality , Glutathione Transferase/genetics , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/mortality , Isoenzymes/genetics , Polymorphism, Genetic , DNA-Binding Proteins/genetics , Female , Genotype , Glutathione S-Transferase pi , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Prognosis , Proportional Hazards Models , X-ray Repair Cross Complementing Protein 1ABSTRACT
PURPOSE: Markers of somatic mutation such as p16 and p53 remain controversial prognostic indicators for patients with squamous cell carcinoma of the head and neck (SCCHN). The relationship between p53 protein expression and radiation therapy is also unclear. EXPERIMENTAL DESIGN: We made a prospective cohort study (n = 171) of incident cases receiving standardized therapy for SCCHN. RESULTS: Patients whose tumors showed increased p53 protein expression had over twice the risk of all-cause mortality after 550 days [hazard ratio (HR), 2.7; 95% confidence interval (CI), 1.07-6.66] and three times the risk of dying from cancer-specific causes after 550 days (HR, 3.09; 95% CI, 1.15-8.30) after adjustment for age, therapy, and stage. Tumors demonstrating alteration of both p16 and p53 did not confer any additional diagnostic information over p53 alone. Patients whose tumors expressed increased levels of p53 protein and received radiation were almost three times more likely to die as compared with those who received radiation but whose tumors did not express increased p53 protein after adjustment for age and stage (HR, 2.6; 95% CI, 1.03-6.50). CONCLUSIONS: p53 protein expression was found to violate the proportional hazards assumption for our cohort, which may explain the controversial prognostic ability of this protein in the literature. p53 protein expression, but not p16 protein expression, was related to poor survival in general for men and women. In addition, an interaction between p53 expression and radiation therapy was demonstrated. Additional studies are needed to confirm and extend our results.
