Abstract
Introduction: Every year, more than 10 million women are diagnosed worldwide with breast cancer. Breast cancer remains the leading cause of death from malignancy in women. In Mexico about 12 Mexican women die every day from this disease. Glutathione S-transferase (GST) family consists of a group of isoenzymes involved in Phase II detoxification of xenobiotics by glutathione conjugation. There have been reports showing GST polymorphisms as a risk factor for developing cancer. Objective: Determine if the frequencies of polymorphisms of GSTT1, GSTM1 and GSTP1 are associated with breast cancer development. Materials and Methods: We studied 22 women with breast cancer and a control group of 30 women. DNA was extracted from blood. Polymorphisms of T1 and M1 were identified by multiplex PCR. The identification of GSTP1b (exon 5) and GSTP1c (exon 6), was performed separately by RFLP-PCR, using BsmAI and AciI enzymes respectively. Results: Frequencies of polymorphisms were as follows: for breast cancer group 33% null GSTT1 vs 40% null in the control, 32% null GSTM1 vs 63% of control; 63% heterozygote GSTP1b P1a/P1b and 18% homozygote P1b/P1b, vs 53% heterozygote and 20% homozygote in the control, 41% heterozygote P1a/P1c GSTP1c and 0% homozygote vs 10% heterozygote P1c/P1c and 0% homozygote control. Significant differences were found between GSTM1 and GSTP1c polymorphisms with GSTM1 null percentage higher in the control group and a higher frequency of P1c heterozygotes in the cancer group. Conclusion: As this is a pilot study where the results showed no association with breast cancer, further investigation is required on the involvement of GST genes in neoplasm development.
Highlights
Every year, more than 10 million women are diagnosed worldwide with breast cancer
Frequencies of polymorphisms obtained for the breast cancer group were: 77% wild GSTT1 and 33% null; 68% was wild GSTM1 and 32% null, while in the control group 60% was wild GSTT1 and 40% null; 37% was wild GSTM1 and 63% null
Upon examination of our results for each gene individually, we found a significant difference of frequencies for GSTM1 between the two groups, since the wild type allele had a greater presence in the breast cancer group than in the control group, these results are similar to those obtained by Zheng et al (2003), in a study of 326 patients with this neoplasm, finding an association between wild GSTM1 and alcohol consumption with susceptibility to breast cancer [33]
Summary
Breast cancer remains the leading cause of death from malignancy in women. The presence of polymorphisms or variations in the base sequences of metabolic genes give rise to variable enzyme activity which leads to differing abilities in the metabolism of xenobiotics [6], of which the glutathione S-transferase family (GST) is a part. It consists of several genes coding for a group of isozymes involved in Phase II metabolism, protecting the cell from oxidative injury [7]-[10]. The most studied GST subclasses in mammals are Mu (μ), Pi (π) and Theta (θ) [11] [12]
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