A novel polymorphism in intron 6 of the human p53 gene: a possible association with cancer predisposition and susceptibility.

We present a novel polymorphic 8-bp sequence in intron 6 of the p53 gene that maps between bp 55 and 62 of the 3' end of exon 6. Of normal blood samples, 32% were heterozygotic for this polymorphism and display a NN' genotype, whereas 68% of the population is homozygotic for the N genotype. The rare homozygotic genotype N' was detected only in four blood samples of cancer patients. Peripheral blood of gastrointestinal (GI) and breast tumor patients demonstrated a higher incidence of heterozygosity (50%) than that of normal individuals. Analysis of the distribution of this polymorphism in tumor samples showed loss of heterozygosity (LOH). This LOH during tumor progression could exhibit preference to each one of the polymorphic alleles. The rare presentation of one allele and the increased incidence of heterozygosity in carcinoma patients may suggest an association between this polymorphism with cancer predisposition and susceptibility. The fact that genetic alterations occurring in noncoding regions may play a role in tumor development only further increases the extent of involvement of p53 in carcinogenesis.