Crosstalk of Cyclin-dependent kinase inhibitor 1A (CDKN1A) gene polymorphism with p53 and CCND1 polymorphism in breast cancer

OBJECTIVE: Mutations and polymorphisms in genes of cell- cycle and apoptosis regulatory pathway influence the breast cancer risk. Analysis of single low penetrance mutant alleles may not reflect the precise risk association when analyzed alone. PATIENTS AND METHODS: A total of 115 DNA samples extracted from breast cancer patients and an equal number of age and sex-matched normal controls were used for polymorphic analysis. Genotyping for p21 rs1801270 and CCND1 rs603965 was done by PCR-RFLP method while AFLP method was used for p53 rs1042522 single nucleotide polymorphism detection. Statistical methods included simple mean +/- SD and correlation coefficient to analyze the risk of association of p21, p53 and CCND1 SNPs and breast cancer. RESULTS: Individuals harboring SNPs in p21, p53 and CCND1 genes namely rs1801270, rs1042522 and rs603965, respectively were rendered increasingly susceptible to developing breast cancer when compared with normal controls. CONCLUSIONS: Our report emphasizes the need of combinational analysis of low-penetrance mutant alleles to assess accurately their association with breast cancer risk. Future case-control studies analyzing gene-environment interactions across different populations may confirm reported risk associations of studied polymorphisms with developing breast cancer.