H. Makni et al., p53 polymorphism in codon 72 and risk of human papillomavirus-induced cervical cancer: Effect of inter-laboratory variation, INT J CANC, 87(4), 2000, pp. 528-533
An association between codon-72 p53 polymorphism and risk of human papillom
avirus (HPV)-induced cervical cancer has been found recently, but it has be
en difficult to replicate. In this study, we assess the impact of inter-lab
oratory variation in p53 genotyping on the validity of the proposed associa
tion. DNA specimens were randomly selected from 54 invasive, squamous cell
carcinoma cases, 52 HPV-negative, and 39 HPV-positive controls from a previ
ous case-control study in Brazil. Codon-72 polymorphism was blindly analyze
d in three different laboratories. We calculated age- and race-adjusted odd
s ratios (OR) and 95% confidence intervals (CI) using logistic regression f
or gauging the association between p53 polymorphism and cervical cancer ris
k. The proportions of the Arg/Arg, Arg/Pro, and Pro/Pro genotypes varied su
bstantially among laboratories with Kappa coefficients in the 0.49-0.63 ran
ge. When disagreement between labs was allowed, the OR for the Arg/Arg geno
type, compared to other forms, was as low as 1.5 (95% CI: 0.5-3.9). In cont
rast, the OR increased to 8.0 (95% CI: 2.3-28.5) after exclusion of discord
ant genotypes. Restricting the comparison to HPV-positive controls increase
d the magnitude of the relation appreciably. After exclusion of all discord
ant diagnoses, the OR was 21.5 (95% CI: 3.4-137.8), whereas with disagreed
genotypes the association was not significant (OR = 2.9, 95% CI: 0.7-11.9).
Homozygous codon-72 p53-Arg apparently confers a higher susceptibility to
HPV-associated cervical tumorigenesis. However, exposure misclassification
consequent to inter-laboratory variation in protocols may affect the abilit
y to detect the association. Int. J. Cancer 87:528-533, 2000. (C) 2000 Wile
y-Liss, Inc.