Codon 72 and G13964C intron 6 polymorphisms of TP53 in relation to development and progression of breast cancer in India.

The p53 protein is at the center of cell regulatory pathways influencing transcription and activity of several replication and transcription factors. In exon 4 of the gene TP53, a codon 72 polymorphism causing an Arg/Pro substitution has been reported in breast and other cancers. This substitution is in the putative SH3 binding domain of p53 protein, influencing binding capacity and thereby functional properties. In the present investigation of a relatively large series of cases in India, the frequency of the homozygous arginine genotype (33.2%) was significantly higher in the breast cancer group as compared to controls (19.6%), χ2 =11.791 (P=0.003). Patients with premenopausal breast cancer had a more elevated frequency (41.1%) than postmenopausal cases (25.4%) although the genotype frequency distribution did not show significant variation with respect to hormonal receptor status. Elevation was greatest in patients in advanced stages of cancer. The hetrozygote frequency (Arg/Pro) was also found to be increased in overweight and obese women with breast cancer. TP53 codon 72 polymorphism might predispose individual for the development of breast cancer as well as to bad prognosis. Intronic variants may affect gene regulation through aberrant splicing or through disruption of critical DNA-protein interaction. While no significant association was observed with relation to CC genotype as well as C allele of G13964C intron polymorphism with breast cancer, the C allele frequency showed association with respect to other risk confounding factors which might play role in progression of breast cancer.