P53 POLYMORPHISMS AND HAPLOTYPES IN LUNG-CANCER

An association between the BstU I 1-1 (Pro-Pro) genotype of the p53 co don 72 polymorphism and lung cancer has previously been reported by Ka wajiri et al, A reanalysis of the data by Kawajiri et al. revealed no significant difference between patients and controls with respect to a llele frequencies, and the increased frequency of BstU I 1-1 homozygot es was mostly ascribable to a deviation from the Hardy-Weinberg equili brium. In an attempt to replicate the results by Kawajiri et al. we ha ve studied three p53 polymorphisms (BstU I and Msp I RFLPs in exon 4 a nd intron 6 respectively and a 16 bp duplication in intron 3) and thei r haplotypes in Swedish lung cancer patients and controls, The results concerning the codon 72 polymorphism were largely negative, Thus ther e 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 B stU I allele frequency when lung cancer patients were compared with pa tients with chronic obstructive pulmonary disease (COPD), However, whe n the analysis was based on haplotype frequencies larger differences a ppeared 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 again st cancer. Thus the codon 72 alleles need not be functionally involved in lung cancer, but may rather be markers in linkage disequilibrium w ith other cancer susceptibility sites on p53.