Huncharek M, Kupelnick B, Geschwind J F, Caubet J F
Division of Radiation Oncology, Marshfield Clinic Cancer Center/St. Michael's Hospital, 900 Illinois Avenue, Stevens Point, WI 54481, USA.
Cancer Lett. 2000 May 29;153(1-2):219-26. doi: 10.1016/s0304-3835(00)00381-5.
Mutation of the p53 tumor suppressor gene is considered a possible marker of poor survival among patients with non-small cell lung cancer (NSCLC). This report presents the results of a meta-analysis of the available data addressing this issue. Using previously described methods, a protocol was developed for a meta-analysis examining the prognostic significance of p53 mutations in NSCLC. Two-year survival data derived from 829 patients in eight published studies were analyzed using a general variance-based method employing confidence intervals described by Greenland (Epidemiol. Rev. 9 (1986) 1-30). The outcome of interest was a summary relative risk (RRs) reflecting the risk of death at 2 years associated with p53 mutation positive versus p53 negative disease. Prior to calculation of a RRs, an analysis for homogeneity (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 1.52 was found when all eight studies were combined (favoring a negative prognostic role for p53 mutation), the validity of this estimate is questionable since the existing heterogeneity indicates that factors other than p53 mutation account for the variability in RRs across studies. Sensitivity analyses suggested that selection bias might represent an important source of variability in that p53 mutations may differ in their effects on biological behavior of NSCL tumors. Other possible confounders include smoking history, race, geographic location of study and socio-economic 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 control for possible confounders in order to determine whether certain p53 mutations are truly associated with poor clinical outcome.
p53肿瘤抑制基因的突变被认为是非小细胞肺癌（NSCLC）患者生存预后不良的一个可能标志物。本报告呈现了针对该问题的现有数据的荟萃分析结果。采用先前描述的方法，制定了一项荟萃分析方案，以检验p53突变在NSCLC中的预后意义。使用基于一般方差的方法，采用Greenland描述的置信区间（《流行病学评论》9 (1986) 1 - 30），对八项已发表研究中829例患者的两年生存数据进行了分析。感兴趣的结果是一个汇总相对风险（RRs），反映p53突变阳性与p53阴性疾病相比在两年时的死亡风险。在计算RRs之前，同质性分析（Q）显示Q等于22.3。自由度为8时，这产生了一个对应的P值，P<0.005。这表明各研究在效应估计方面存在实质性异质性。尽管八项研究合并时发现RRs为1.52（支持p53突变具有负面预后作用），但该估计的有效性值得怀疑，因为现有的异质性表明除p53突变外的其他因素导致了各研究中RRs的变异性。敏感性分析表明，选择偏倚可能是变异性的一个重要来源，因为p53突变对NSCL肿瘤生物学行为的影响可能不同。其他可能的混杂因素包括吸烟史、种族、研究的地理位置和社会经济地位。现有数据不支持p53突变作为NSCLC预后标志物的明确作用。似乎多种偏倚来源可能导致p53突变状态与生存之间的虚假关联。未来的分析必须控制可能的混杂因素，以确定某些p53突变是否真的与不良临床结局相关。
