Glutathione S-transferases deletions may act as prognosis and therapeutic markers in breast cancer

Abstract

Breast cancer (BC) is the main worldwide neoplasia in women. The metabolic balance between xenobiotic absorption and elimination rates plays an important role in preventing DNA damage and, consequently, tumor development. The glutathione S-transferases (GSTs), such as GSTM1 and GSTT1, and the NAD(P)H quinone oxidoreductase are important enzymes involved in phase II detoxification reactions. Deletions in GSTM1 and GSTT1, and single-nucleotide polymorphism (SNP) in NQO1 (rs1800655) have been investigated in cancer context, revealing conflicting results. The present study analyzed these genetic polymorphisms in 121 BC patients and 151 BC-free controls in order to verify if they could act as susceptibility modifiers and/or prognostic factors. Binary logistic regressions adjusted by age were performed to assess associations between allelic variants and interactions in polymorphisms combination with BC susceptibility, but no significant association was found. Genotypes distribution was also compared between BC subtypes, but no significant difference was observed (p > 0.05). GSTM1 deletion was significantly associated with histopathological grade, with a greater proportion of patients presenting grade III tumors (p = 0.007). Univariate analysis identified tumor size as the only clinicopathological parameter potentially associated with recurrence risk in patients that received adjuvant chemotherapy (p < 0.1). Thus, logistic regression analysis adjusted by tumor size revealed a positive association between GSTT1 deletion and recurrence risk in general BC (OR 4.25; p = 0.04), while GSTM1 was negatively associated with recurrence risk in ER/PRHER2 samples (OR 0.07; p = 0.03). In conclusion, the present study indicated that GSTT1 deletion was associated with increased recurrence risk, while GSTM1 correlated with worst prognosis parameters at diagnosis, but was negatively associated with recurrence risk in luminal subtype samples.

Primary 21-Gene Recurrence Score and Disease Outcome in Loco-Regional and Distant Recurrent Breast Cancer Patients

“…Previous studies have demonstrated that single gene expression in 21-gene RS panel was associated with survival in early BC patients. GSTM1 (35,36), ER, and PR (37) were associated with better outcome, while CD68 (38) and GRB7 (39) was related with worse prognosis. In our study, we found that PR and GSTM1 was independently associated with superior disease outcome.…”

GSTT1, GSTP1, and GSTM1 genetic variants are associated with survival in previously untreated metastatic breast cancer

“…However, drug-resistance remains a crucial obstacle to tackle [ 24 ]. What is more, the potential of biomarker-based treatments improving target therapies, emphasized the requirement to find molecular markers involved in pathogenesis of breast cancer, which are the prognostic factors of therapeutic response and survival [ 25 ].…”

Global Quantification of Glutathione S-Transferases in Human Serum Using LC-MS/MS Coupled with Affinity Enrichment

“…Even though quantification scales differed, the abundance order of GSTs in serum obtained by our newly developed method was similar to that obtained from ELISA, indicating that the two assays are consistent. GSTT1 and MGST1 were first quantified in human serum using strong and reliable MS signals, and these two GSTs have been linked to diseases; therefore, their abundance in serum merits further attention. − …”