GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis

Abstract

Observational studies have reported controversial results on the association between GSTT1 and GSTM1 genotypes and treatment outcome of breast cancer. The purpose of this study is to evaluate the association between GSTT1 and GSTM1 and treatment outcome in breast cancer patients. Eligible studies were searched in PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases. A random-effect model or fixed-effect model was used to calculate the overall combined risk estimates. Twenty-one studies with a total of 4990 patients were included in this meta-analysis. The GSTM1 null genotype (odds ratio (OR) = 1.33, 95 % confidence interval (CI) 1.01-1.75, P = 0.046) and GSTT1/GSTM1 double null genotype (OR = 2.22, 95 % CI 1.02-4.84, P = 0.045) were significantly associated with an increased tumor response. A reduced overall survival (hazard ratio (HR) = 0.84, 95 % CI 0.72-0.98, P = 0.024) was observed in GSTM1 null genotype, especially in mixed descent (HR = 0.77, 95 % CI 0.61-0.96, P = 0.018) and large sample size (HR = 0.85, 95 % CI 0.72-0.99, P = 0.033). Evidence of publication bias was observed in GSTM1 genotype rather than in GSTT1 genotype. This meta-analysis suggests that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response. However, the GSTM1 null genotype might be significantly associated with a reduced overall survival. Future studies are warranted to confirm these findings.

GSTP1andABCB1Polymorphisms Predicting Toxicities and Clinical Management on Carboplatin and Paclitaxel‐Based Chemotherapy in Ovarian Cancer

“…41 The frequencies of hematological toxicities, such as anemia, leukopenia, neutropenia, and thrombocytopenia, were variable in previous studies. 4,14,[17][18][19]26,27,41,42 The poor tolerance of thrombocytopenia (grade 1-above) differs from the other hematological toxicities because it was classified according to platelet counts < 75,000/mm 3 and literature. 19,42,43 Perhaps different frequencies of hematological toxicities are related to the timing of blood sample collection.…”

“…19,42,43 Perhaps different frequencies of hematological toxicities are related to the timing of blood sample collection. 14,41 In our study, hematological toxicity was scored based on samples collected before each cycle of chemotherapy (about 21 days) to determine the recovery of red blood cells, neutrophils, and platelets. Previous studies have demonstrated the association between chemotherapy-related severe anemia and thrombocytopenia and the GSTP1 c.313A>G polymorphism in patients who received carboplatin and paclitaxel-based chemotherapy.…”

“…Consequently, individuals homozygous for the GSTM1 or GSTT1-null allele have a complete absence of GSTM1 and GSTT1 activity, whereas individuals with two copies of the GSTM1 or GSTT1 genes have reference protein levels. 12,13 There is some evidence that these deletion genotypes may play a role in toxicity, response to treatment, and survival in some cancers, [14][15][16] including cancer of the ovary. 8 In contrast to the commonly studied GSTM1 and GSTT1 genotypes, the GSTP1 c.313A>G (rs1695) is an exonic single nucleotide polymorphism (SNP) that causes an amino acid substitution and results in an isoleucine to valine (Ile > Val) change at codon 105 of the enzyme.…”

Prognostic Impact of the Tumor Marker CA 15-3 in Patients With Breast Cancer and Bone Metastases Treated With Palliative Radiotherapy

“…Their main focus was on circulating tumor cells, which contributed better prognostic information than CA 15-3. Other innovative markers are also of considerable interest [ 20-23 ]. However, none of these are part of routine clinical practice yet.…”

Genetic variants and increased risk of meningioma: an updated meta-analysis

“…For instance, GSTM1 and GSTT1 polymorphisms might be associated with renal cell carcinoma risk or treatment outcomes of breast cancer 48,4951.…”