GSTP1 methylation and polymorphism increase the risk of breast cancer and the effects of diet and lifestyle in breast cancer patients

Saxena, Anubha and Dhillon, Varinderpal S. and Shahid, Mohammad and Saleh Khalil, Hesham and Rani, Madhu and Das, Trinath Prasad and Hedau, Suresh and Hussain, Arif and Naqvi, Raza Ali and S.V.S, Deo and N.K, Shukla and B.C, Das and Husain, Syed Akhtar (2012) GSTP1 methylation and polymorphism increase the risk of breast cancer and the effects of diet and lifestyle in breast cancer patients. EXPERIMENTAL AND THERAPEUTIC MEDICINE. pp. 1097-1103.

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Abstract

Glutathione S-transferases (GSTs) are an important group of isoenzymes that play an essential role in the detoxification of carcinogens. Polymorphism at exon 5 of the GST π family decreases the catalytic activity and affects the detoxification ability of the enzyme, GSTP1. GSTP1 promoter hypermethylation and loss of expression are frequently observed in various types of carcinoma. We hypothesized that somatic epigenetic modification in homozygous mutants increases the degree to which breast cancer risk is affected by lifestyle factors and dietary habits. The present study used tumor biopsies and blood samples from 215 breast cancer patients and 215 blood samples from healthy donors. GSTP1 polymorphism was studied using PCR-restriction fragment length polymorphism, methylation using methylation‑specific PCR and loss of expression using immunohistochemistry and western blotting. No significant increase was observed in the breast cancer risk of individuals with the mutant (Val) allele [odds ratio (OR), 1.48; 95% confidence interval (CI), 0.97‑2.26 for heterozygotes; OR, 1.42; 95% CI, 0.86‑2.42 homozygous mutants]. GSTP1 promoter hypermethylation was detected in one-third of tumor biopsies (74/215) and was found to be associated with a loss of expression. Genotype and tumor methylation associations were not observed. Estrogen (ER) and progesterone (PR) receptor‑positive tumors had a higher methylation frequency. GSTP1 polymorphism was not associated with increased promoter hypermethylation. The results suggest that GSTP1 methylation is a major event in breast carcinogenesis and may act as a tumor‑specific biomarker.

Item Type: Article
Subjects: Engineering > Dubai Campus > School of Life Sciences
Depositing User: Admin MU Dubai
Date Deposited: 18 Mar 2015 12:27
Last Modified: 22 Mar 2015 05:53
URI: http://eprints.manipal.edu/id/eprint/142212

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