P53 POLYMORPHISMS AND HAPLOTYPES IN BREAST-CANCER

Three polymorphisms in the human tumor suppressor gene p53 (BstUI and MspI RFLPs in exon 4 and intron 6 respectively and a 16 bp duplication in intron 3) and their haplotype combinations were studied in patient s with breast cancer and controls. A significant increase in the codon 72 BstUI A1 (pro) allele frequency (P = 0.016) and of individuals car rying the pro allele (pro/pro and pro/arg) (OR, 1.47; P = 0.014; 95% C I, 1.08-2.00) was observed in breast cancer. This increase was most pr onounced in highly differentiated breast cancer. Significant associati ons were found only in BstUI and haplotypes containing this polymorphi sm, which indicates that the codon 72 pro allele may be functionally i nvolved in low malignancy breast cancer. The distributions of genotypi c combinations in breast cancer patients and controls were significant ly different (P = 0.005). Two BstUI-16 bp-MspI combinations were signi ficantly overrepresented; 2-1, 1-1, 2-2 (OR, 1.61; 95% CI, 1.13-2.30) and 1-1, 2-1, 2-1 (OR, 2.94; 95% CI, 1.37-6.27).