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

Saxena,Anubha; Dhillon,Varinderpal  S.; Shahid,Mohammad; Khalil,Hesham Saleh; Rani,Madhu; Das,Trinath Prasad; Hedau,Suresh; Hussain,Arif; Naqvi,Raza Ali; Deo,S. V.S.; Shukla,N. K.; Das,B. C.; Husain,Syed Akhtar

doi:10.3892/etm.2012.710

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

Authors:
- Anubha Saxena
- Varinderpal S. Dhillon
- Mohammad Shahid
- Hesham Saleh Khalil
- Madhu Rani
- Trinath Prasad Das
- Suresh Hedau
- Arif Hussain
- Raza Ali Naqvi
- S. V.S. Deo
- N. K. Shukla
- B. C. Das
- Syed Akhtar Husain
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Affiliations: Human Genetics Laboratory,Department of Biosciences, Jamia Millia Islamia (A Central University), New Delhi, India, CSIRO Food and Nutritional Sciences, Adelaide, Australia, College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia, School of Biotechnology, Jawaharlal Nehru University, New Delhi, Institute of Cytology and Preventive Oncology, Noida, Department of Surgical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India, Department of Surgical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Published online on: September 17, 2012 https://doi.org/10.3892/etm.2012.710
Pages: 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.

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