Analysis of epigenetic alterations in the promoter regions of TIMP3 and GSTP1 genes in sporadic breast cancer

Objective: Tissue Inhibitor of Metalloproteinases-3 (TIMP3) and Glutathione S-transferase P1 (GSTP1) are tumor suppressor genes, which play important role in regulation of extracellular matrix proteolysis and cellular detoxification from various xenobiotic drugs and carcinogens. Aberrant methylation of tumor suppressor gene at the promoter regions can inactivate its expression, which is important in the carcinogenesis of various cancer including breast cancer. Hence the present study was designed to determine the role of promoter methylation of TIMP3 and GSTP1 genes in sporadic breast cancer patients from South Indian population. Materials and Methods: DNA methylation analyses of TIMP3 and GSTP1 gene were performed by methylation-specific polymerase chain reaction (MSP). Fifty biopsy samples of breast tumor and their corresponding non-malignant portions as controls were studied. mRNA expression analysis of these two genes were also done using real time PCR. Results: Methylation of the TIMP3 promoter was detected in 18% (9/50) and GSTP1 promoter was detected in 20% (10/50) tumor samples. None of the normal tissues showed promoter hypermethylation in both the genes. The difference in methylation frequency between cancerous and normal tissue was statistically significant (p = 0.0029 and p =0.0013). GSTP1 promoter methylation was positively associated with lymph node involvement (p = 0.034) and metastasis(p = 0.036). Any significant association was not found between TIMP3 promoter hypermethylation and clincopathalogical parameters. Conclusion: In conclusion, this study showed that promoter hypermethylation of TIMP3 and GSTP1 genes were associated with sporadic breast cancer patients from the South Indian population and may be useful as a new biomarker for breast cancer detection.