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 betw een smoking and p53 tumor suppressor gene alterations, and their associatio n with clinicopathologic features and prognosis in non-small cell lung canc er (NSCLC). METHODS: For 111 of 119 stage I-III NSCLC patients that had been followed p rospectively, tumor p53 protein accumulation was measured immunohistochemic ally (IHC). Staining was evaluated as a score (p53(IHCS)) combining intensi ty and percent distribution. RESULTS: Forty-eight of 111 (43%) tumors had p53(IHCS) > 1. p53 IHC was ass ociated 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 [adjus ted odds ratio (OR)5.90, 95% confidence interval (CI) 2.34-14.90]. p53 IHC was not associated with smoking: variables. In multivariate proportional ha zards analysis, p53(IHCS) and pack-years smoked (PY), both as continuous va riables, 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 dise ase (DRD) were 1.35 (95% CI 1.11-1.64) and 1.03 (95% CI 1.01-1.04), respect ively. Comparing the 75(th) percentile to the baseline 0, the adjusted HR f or p53(IHCS) (5 vs. 0) was 4.5 and for PY (55 vs. 0) was 5.1 for thr outcom e DRD. Both variables demonstrated a dose-response relationship with surviv al. CONCLUSIONS: PY and p53(IHCS) are significant, independent and important pr edictors of recurrence and DRD in stage I-III NSCLC. Ann Epidemiol 2000;10: 176-185. (C) 2000 Elsevier Science Inc. All rights reserved.