Background: Genetic polymorphisms and mutations of the genes involved in tumorigenesis may determine individual susceptibility for cancer. The p27/Kip1 protein belongs to the family of cyclin-dependent kinase-inhibitory proteins, which are negative regulators of cell-cycle progression. Reduced protein levels of p27/Kip1 have been reported in numerous human cancers including breast cancer.
Methods and results: p27 gene mutations and the codon 109 polymorphism were investigated in breast cancer patients by single strand conformation polymorphism analysis, PCR-restriction fragment length polymorphism analysis and DNA sequencing. Mutations were identified in 2 of 24 breast tumor samples. One G-->A transition resulting in a silent mutation and a single base deletion resulting in a nonsense mutation were detected in one patient. Another breast cancer sample harbored a T-->A transition at codon 159. An association between the codon 109 B allele and breast cancer was observed.
Conclusion: Our study indicates that mutational alterations in the p27 gene are rare in human breast cancer. The codon 109 B allele is associated with high-grade tumors.