A study of smoking, p53 tumor suppressor gene alterations and non-small cell lung cancer

PURPOSE: The purpose of this study was to investigate the relationship between smoking and p53 tumor suppressor gene alterations, and their association with clinicopathologic features and prognosis in non-small cell lung cancer (NSCLC). METHODS: For 111 of 119 stage I-III NSCLC patients that had been followed prospectively, tumor p53 protein accumulation was measured immunohistochemically (IHC). Staining was evaluated as a score (p53(IHCS)) combining intensity and percent distribution. RESULTS: Forty-eight of 111 (43%) tumors had p53(IHCS) > 1. p53 IHC was associated with increasing tumor size (T) (p = 0.035), nodal status (N) (p = 0.091), stage (p = 0.054), and histology: squamous cell carcinoma (70%) and adenocarcinoma (27%) (p = 0.0002). In logistic regression analysis, p53 IHC was associated with squamous cell histology versus other histotypes [adjusted odds ratio (OR)5.90, 95% confidence interval (CI) 2.34-14.90]. p53 IHC was not associated with smoking: variables. In multivariate proportional hazards analysis, p53(IHCS) and pack-years smoked (PY), both as continuous variables, were negative prognostic factors. The adjusted hazard ratios (HR) for the survival outcome recurrence for p53(IHCS) and PY were 1.20 (95% CI 1.02-1.40) and 1.03 (95% CI 1.01-1.04), and for death due to recurrent disease (DRD) were 1.35 (95% CI 1.11-1.64) and 1.03 (95% CI 1.01-1.04), respectively. Comparing the 75(th) percentile to the baseline 0, the adjusted HR for p53(IHCS) (5 vs. 0) was 4.5 and for PY (55 vs. 0) was 5.1 for thr outcome DRD. Both variables demonstrated a dose-response relationship with survival. CONCLUSIONS: PY and p53(IHCS) are significant, independent and important predictors of recurrence and DRD in stage I-III NSCLC. Ann Epidemiol 2000;10:176-185. (C) 2000 Elsevier Science Inc. All rights reserved.