Prospective Case–Control Study to Evaluate the Role of Glutathione S Transferases (GSTT1 and GSTM1) Gene Deletion in Breast Carcinoma and Its Prognostic Significance

Abstract

Breast cancer is the most common cause of cancer death in women with the incidence rising in young women. GST gene polymorphisms are significant because of their role in the detoxification of both environmental carcinogens and also cytotoxic drugs used in therapy for breast cancer. The present study has been designed to identify the role of polymorphisms in GSTT1 and GSTM1 genes in the risk of development of breast cancer, in the prognostication of breast cancer, and in the prediction of response towards chemotherapy. Ninety-nine patients with breast cancer and 100 healthy controls with no history of cancer were taken from blood donors after informed consent. Epidemiological and clinical data was collected from participants and 5 ml of peripheral venous blood was collected for genotype analysis. Null genotype of GSTT1 was detected in 51.04 % of the controls in comparison to 20.2 % of patients with carcinoma breast, which was found to be statistically significant (OR 4.18; 95 % CI 2.01-8.75; P=0.0001). GSTM1 gene deletion was also significantly more common among controls (60 %) than in patients with breast cancer (33 %) (OR 4.57; 95 % CI 2.20-9.51; P=0.0001). Tumors more than 5 cm in size had greater tendency for GSTM1 gene expression (P value=0.019), but other clinicopathological parameters did not show any correlation. GSTT1 and GSTM1 genes status did not show any association with response to chemotherapy. The results indicated the null genotype of both GSTT1 and GSTM1 to be protective for the development of carcinoma breast. None of the known etiological factors have any correlation with GSTT1 and GSTM1 gene deletion. Patients with small tumor size expressed GSTM1 gene deletion. Other tumor characteristics and clinicopathological parameters did not have any correlation with gene deletion.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) variants and breast cancer risk in Burkina Faso

“…In contrast, in an Indian population, the GSTT1/GSTM1 double null genotype was found to be protective against the development of carcinoma breast and did not show any association with response to chemotherapy. However, tumors more than 5 cm in size were associated with increased GSTM1 gene expression [35]. Thus our study, which does not find an association between breast cancer risk and these variants, is consistent with some of the results of previous studies.…”

“…In our study, GSTM1 and GSTT1-null genotypes were not associated with increased breast cancer risk. Indeed, on the strong association between GSTM1-and GSTT1-null genetic variants and breast cancer, study results have not yet converged [27][28][29]. Thus, in a meta-analysis of 10,067 cancer cases and 12,276 controls, GSTM1-null and GSTT1-null variants are associated with an increased risk of breast cancer in Asians [30].…”

The signature of pharmaceutical sensitivity based on ctDNA mutation in eleven cancers

“…30,31 Bansal et al. 28 have proposed that GSTM1 gene deletion was significantly correlated with breast cancer in 2015, 28 and our study further illustrated that GSTM1 gene deletion was associated with poor prognosis in breast cancer compared with those without this mutation. And NRAS mutation has been studied to have prognostic values in colorectal cancer patients.…”

“…GSTM1 genetic variants have been proved associated with the survival in breast cancer 28,29 and many other cancers. 30,31 Bansal et al.…”

Glutathione S-Transferase T1 and M1 Gene Polymorphisms among Breast Cancer Susceptible Ghanaians

“…The null genotypes lack the gene products, GSTT1 and GSTM1 enzymes [16,22] and thus a total absence of the respective enzyme activity. The noted GST polymorphism and its association with risk of developing breast cancer has been a focus for research scientists and has drawn growing attention but the results have been varying and inconclusive [23]. GSTM1 gene polymorphism has been associated with point mutation and shows variable distribution among populations [17,20].…”