M. Huncharek et al., Prognostic significance of p53 mutations in non-small cell lung cancer: a meta-analysis of 829 cases from eight published studies, CANCER LETT, 153(1-2), 2000, pp. 219-226
Mutation of the p53 tumor suppressor gene is considered a possible marker o
f poor survival among patients with non-small cell lung cancer (NSCLC). Thi
s report presents the results of a meta-analysis of the available data addr
essing this issue. Using previously described methods, a protocol was devel
oped for a meta-analysis examining the prognostic significance of p53 mutat
ions in NSCLC, Two-year survival data derived from 829 patients in eight pu
blished studies were analyzed using a general variance-based method employi
ng confidence intervals described by Greenland (Epidemiol. Rev. 9 (1986) 1-
30). The outcome of interest was a summary relative risk (RRs) reflecting t
he risk of death at 2 years associated with p53 mutation positive versus p5
3 negative disease. Prior to calculation of a RRs, an analysis for homogene
ity (Q) showed Q to equal 22.3, With 8 degrees of freedom, this yielded a P
value corresponding to P < 0.005, This indicated substantial heterogeneity
across studies in terms of their estimate of effect, Although a RRs of 1.5
2 was found when all eight studies were combined (favoring a negative progn
ostic role for p53 mutation), the validity of this estimate is questionable
since the existing heterogeneity indicates that factors other than p53 mut
ation account for the variability in RRs across studies. Sensitivity analys
es suggested that selection bias might represent an important source of var
iability in that p53 mutations may differ in their effects on biological be
havior of NSCL tumors. Other possible confounders include smoking history,
race. geographic location of study and socioeconomic status. The available
data do not support a clear role for p53 mutation as a prognostic marker in
NSCLC. It appears that multiple sources of bias may contribute to spurious
association of p53 mutation status and survival. Future analyses must cont
rol for possible confounders in order to determine whether certain p53 muta
tions are truly associated with poor clinical outcome. (C) 2000 Elsevier Sc
ience Ireland Ltd. All rights reserved.