The association of glutathione S-transferase polymorphisms in patients with osteosarcoma: evidence from a meta-analysis

Abstract

Osteosarcoma is a life-threatening malignancy that often occurs in teenagers. Numerous studies have reported glutathione S-transferase polymorphisms are associated with osteosarcoma, but the results are inconclusive, partially because the sample size in each of published studies is relatively small. Therefore, we performed a meta-analysis of the published studies to estimate the association more accurately. To preciously examine the association between the glutathione S-transferase polymorphisms and osteosarcoma, we undertook a meta-analysis of six case-control studies. The association between the glutathione S-transferase polymorphisms and osteosarcoma risk was assessed by odds ratios together with their 95% confidence intervals using a fixed-effects model or random-effects model. In addition, hazard ratio was used to measure the relationship between glutathione S-transferase polymorphisms and prognosis in patients with osteosarcoma. We found that there was significant association between the polymorphisms in GSTT1 or GSTM3 (AA versus BB) and osteosarcoma risk. In addition, there is no evidence of association on GSTM1, GSTT1, GSTP1 (IIe/IIe versus IIe/Val) or GSTP1 (IIe/IIe versus Val/Val) polymorphisms with prognosis in osteosarcoma. In conclusion, the GSTT1 and GSTM3 polymorphisms might influence osteosarcoma risk.

Role of pharmacogenetics of drug-metabolizing enzymes in treating osteosarcoma

“…Although not revealed in previous single studies, a metaanalysis indicated an association between homozygous GSTM3*B and OS risk, which however is difficult to be precisely estimated since the p value of this correlation was not reported [60]. Different from the studies discussed above, which all analyzed germline variants, Goricar et al recently assessed GSTP1 polymorphisms and GSTM1 and GSTT1 deletions in tumor tissue of 66 OS patients [70].…”

“…Among these, two studies analyzed pediatric tumors including few patients with OS [58,59]. One recent metaanalysis reanalyzed and discussed all four polymorphisms including six already-published case--control studies [60]. Copy number analysis of GSTT1 and GSTM1 was performed in one study but data did not correlate with clinical parameters [48].…”

“…Even a recent meta-analysis [60] could not overcome [67] Information regarding the number of patients with metastases at diagnosis and the drugs used for treatment are reported in the table when they were provided in the publication. the limits inherent in small studies, which often lack statistically significant p values because of too small patient numbers or because it gives rise to false-positive correlations due to biased data.…”

Contribution of the GSTP1 gene polymorphism to the development of osteosarcoma in a Chinese population

“…For the reported association between GST gene polymorphisms and the development and prognosis of osteosarcoma (Li et al, 2014), two meta-analyses have further evaluated their correlations (Wang et al, 2015b;Han et al, 2015). Specifically, Li et al (2014) reported that the GG genotype of GSTP1 was significantly associated with overall survival of osteosarcoma in a Chinese population.…”

“…Specifically, Li et al (2014) reported that the GG genotype of GSTP1 was significantly associated with overall survival of osteosarcoma in a Chinese population. Wang et al (2015b) conducted a meta-analysis of six case-control studies, and did not find any association between GSTT1 polymorphisms and osteosarcoma risk. However, Han et al (2015) performed a pooled meta-analysis of three case-control studies, and their results revealed a significant association between the GSTT1-null genotype and risk of developing osteosarcoma.…”