title: Accuracy of p53 codon 72 polymorphism status determined by multiple laboratory methods: a latent class model analysis.
abstract: BACKGROUND
  Studies on the association of a polymorphism in codon 72 of the p53 tumour suppressor gene (rs1042522) with cervical neoplasia have inconsistent results. While several methods for genotyping p53 exist, they vary in accuracy and are often discrepant.
  
  
  METHODS
  We used latent class models (LCM) to examine the accuracy of six methods for p53 determination, all conducted by the same laboratory. We also examined the association of p53 with cytological cervical abnormalities, recognising potential test inaccuracy.
  
  
  RESULTS
  Pairwise disagreement between laboratory methods occurred approximately 10% of the time. Given the estimated true p53 status of each woman, we found that each laboratory method is most likely to classify a woman to her correct status. Arg/Arg women had the highest risk of squamous intraepithelial lesions (SIL). Test accuracy was independent of cytology. There was no strong evidence for correlations of test errors.
  
  
  CONCLUSIONS
  Empirical analyses ignore possible laboratory errors, and so are inherently biased, but test accuracy estimated by the LCM approach is unbiased when model assumptions are met. LCM analysis avoids ambiguities arising from empirical test discrepancies, obviating the need to regard any of the methods as a "gold" standard measurement. The methods we presented here to analyse the p53 data can be applied in many other situations where multiple tests exist, but where none of them is a gold standard.
authors: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. walter@mcmaster.ca
authors: Stephen D
authors: SD
authors: Walter
authors: Corinne A
authors: CA
authors: Riddell
authors: Tatiana
authors: T
authors: Rabachini
authors: Luisa L
authors: LL
authors: Villa
authors: Eduardo L
authors: EL
authors: Franco
mesh_terms: D019943:Amino Acid Substitution; D003062:Codon; D005260:Female; D005820:Genetic Testing / Q000379:methods / Q000592:standards; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D015203:Reproducibility of Results; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics
chemical_list: D003062:Codon; D016159:Tumor Suppressor Protein p53