Promoter methylation and genetic polymorphism of glutathione S-transferase P1 gene (GSTP1) in Thai breast-cancer patients

Abstract

The GSTP1 gene encodes for a detoxification enzyme involved in protecting cells from carcinogens. In breast cancer, GSTP1 polymorphisms may produce lower effective enzyme detoxification properties and GSTP1 promoter hypermethylation may result in inactivation of GSTP1 expression. We therefore hypothesized an influence on progression of breast cancer. To study the effect of GSTP1 polymorphisms and CpG-island hypermethylation on GSTP1 promoter, PCR-RFLP and methylation-specific PCR techniques were used with 41 Thai breast-cancer patients. Associations between the codon 105 (A to G) genetic polymorphism, CpG-island hypermethylation, and clinico-pathological parameters were analyzed. GSTP1 hypermethylation was found in 26% of cases and the GSTP1 polymorphism in 14%. GSTP1 hypermethylation was significantly associated with breast cancer; lymph-node metastasis (P = 0.02) while GSTP1 polymorphism status significantly varied with progesterone receptor positivity (P = 0.04). No association was found between the GSTP1 polymorphism and methylation status. The results indicated that CpG-island hypermethylation of the GSTP1 promoter is associated with a biologically aggressive phenotype, but may not be related to the codon 105 (A to G) gene polymorphism in breast-cancer patients.