P53 POLYMORPHISMS AND HAPLOTYPES IN LUNG-CANCER

An association between the BstU I 1-1 (Pro-Pro) genotype of the p53 codon 72 polymorphism and lung cancer has previously been reported by Kawajiri et al, A reanalysis of the data by Kawajiri et al. revealed no significant difference between patients and controls with respect to allele frequencies, and the increased frequency of BstU I 1-1 homozygotes was mostly ascribable to a deviation from the Hardy-Weinberg equilibrium. In an attempt to replicate the results by Kawajiri et al. we have studied three p53 polymorphisms (BstU I and Msp I RFLPs in exon 4 and intron 6 respectively and a 16 bp duplication in intron 3) and their haplotypes in Swedish lung cancer patients and controls, The results concerning the codon 72 polymorphism were largely negative, Thus there was no significant association between lung cancer and the BstU I 1-1 type, and only a marginal difference (P=0.044) with respect to the BstU I allele frequency when lung cancer patients were compared with patients with chronic obstructive pulmonary disease (COPD), However, when the analysis was based on haplotype frequencies larger differences appeared and it was found that only BstU I 1 (pro) alleles linked to 16 bp 1 alleles were associated with lung cancer, Pro alleles linked to the 16 bp duplication appeared instead to confer some protection against cancer. Thus the codon 72 alleles need not be functionally involved in lung cancer, but may rather be markers in linkage disequilibrium with other cancer susceptibility sites on p53.