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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Association between GSTP1 polymorphisms and prognosis of osteosarcoma in patients treated with chemotherapy: a meta-analysis

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          Abstract

          Objective

          The aim of this study was to evaluate the relationship between GSTP1 polymorphisms and prognosis of osteosarcoma in patients treated with chemotherapy, by performing a meta-analysis.

          Methods

          The studies of effects of GSTP1 gene polymorphisms on osteosarcoma survival after chemotherapy were collected. STATA (version 12.0) was used to perform data synthesis.

          Results

          Six studies involving 898 participants were included. A meta-analysis was performed on studies in GSTP1 313A>G(rs1695) assessing the association between tumor response and the polymorphisms in GSTP1 (AA vs AG, AA vs GG), the pooled odds ratios (ORs) were 2.06 (95% confidence interval [CI]: 1.48–2.86, P=0.628, I 2=0.0%). There was significant association between the polymorphisms in GSTP1 (AA vs AG, AA vs GG) and the events that happened, the pooled ORs were 1.86 (95% CI: 1.14–3.06, P=0.034, I 2=58.6%), and there was significant association between the polymorphisms in GSTP1 (AA vs AG, AA vs GG) and survival times (overall survival and progression-free survival) in osteosarcoma patients treated with chemotherapy, and the pooled ORs were 2.14 (95% CI: 1.51–3.04, P=0.675, I 2=0.0%) and 2.77 (95% CI: 1.56–4.91, P=0.347, I 2=9.3%), respectively. Two studies assessed the association of polymorphisms in GSTP1 I105V (IIe/IIe vs IIe/Val, IIe/IIe vs Val/Val) with overall survival in human osteosarcoma. The pooled ORs were 1.20 (95% CI: 0.64–2.27, P=0.010, I 2=73.5%). The study showed an insignificant difference in overall survival for the polymorphisms in GSTP1 (IIe/IIe vs IIe/Val, IIe/IIe vs Val/Val).

          Conclusion

          This meta-analysis indicated that GSTP1 polymorphisms might influence osteosarcoma risk and suggests that GSTP1 polymorphisms may be an important risk factor for osteosarcoma.

          Most cited references12

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          Asthma genetics and genomics 2009.

          Scott Weiss, Benjamin A. Raby, Angela Rogers (2009)
          Asthma Genetic Association studies have been plagued by methodologic problems that are common in all studies of complex traits: small sample size, lack of replication, and lack of control of population stratification. Despite this, the field has identified 43 replicated genes from association studies. The most frequently replicated are: TNF alpha, IL4, FCERB, Adam 33, and GSTP1. Several genes have been identified by linkage and fine mapping (ADAM33, DPP10, GPR154, and PHF11) and one gene has been identified by GWAS (ORMD3). The major issue is that these genes have been looked at one at a time rather than in some more holistic manner where epistasis is considered. For asthma genetics to begin to have an impact on clinical medicine we need to consider epistatic interaction.
          Article 0 comments Cited 27 times – based on 0 reviews     Review now
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            Effect of ABCB1 and ABCC3 Polymorphisms on Osteosarcoma Survival after Chemotherapy: A Pharmacogenetic Study

            Daniela Caronia, ANA PATIÑO-GARCÍA, Antonio Pérez Martínez … (2011)
            Background Standard treatment for osteosarcoma patients consists of a combination of cisplatin, adriamycin, and methotrexate before surgical resection of the primary tumour, followed by postoperative chemotherapy including vincristine and cyclophosphamide. Unfortunately, many patients still relapse or suffer adverse events. We examined whether common germline polymorphisms in chemotherapeutic transporter and metabolic pathway genes of the drugs used in standard osteosarcoma treatment may predict treatment response. Methodology/Principal Findings In this study we screened 102 osteosarcoma patients for 346 Single Nucleotide Polymorphisms (SNPs) and 2 Copy Number Variants (CNVs) in 24 genes involved in the metabolism or transport of cisplatin, adriamycin, methotrexate, vincristine, and cyclophosphamide. We studied the association of the genotypes with tumour response and overall survival. We found that four SNPs in two ATP-binding cassette genes were significantly associated with overall survival: rs4148416 in ABCC3 (per-allele HR = 8.14, 95%CI = 2.73-20.2, p-value = 5.1×10−5), and three SNPs in ABCB1, rs4148737 (per-allele HR = 3.66, 95%CI = 1.85–6.11, p-value = 6.9×10−5), rs1128503 and rs10276036 (r2 = 1, per-allele HR = 0.24, 95%CI = 0.11–0.47 p-value = 7.9×10−5). Associations with these SNPs remained statistically significant after correction for multiple testing (all corrected p-values [permutation test] ≤0.03). Conclusions Our findings suggest that these polymorphisms may affect osteosarcoma treatment efficacy. If these associations are independently validated, these variants could be used as genetic predictors of clinical outcome in the treatment of osteosarcoma, helping in the design of individualized therapy.
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              Genetic polymorphisms in human xenobiotica metabolizing enzymes as susceptibility factors in toxic response.

              H Autrup (2000)
              Biotransformation plays an important role in the carcinogenic activity and organ specificity of environmental carcinogens. Large interindividual variation in the biotransformation has been reported, and genetic polymorphisms in some xenobiotica metabolizing enzymes can in part explain some of these differences. The concentration of the ultimate carcinogen, that will react with DNA, is determined by the rate of activation and detoxification. Individuals with a decreased rate of detoxification, i.e., lacking the glutathione S-transferase M1 gene, have a slightly higher level of bulky carcinogen-DNA adduct in some tissues, and do also have an increased level of chromosomal aberrations. In addition, the genotype may also influence the type of mutations, e.g., in tumor suppressor gene, transversion being predominant in the GSTM1 null group. People with slow N-acetyltransferase activity do generally have a higher adduct level of aromatic amines in bladder tissues. Genetic polymorphism in either CYP1A1 or glutathione S-transferase is linked to an increased risk of smoking related cancers, while N-acetyltransferase activity is related to cancers in which aromatic amines are the main risk factor. Combination of the high risk genotypes for activating and detoxification enzymes, e.g., CYP1A MspI/GSTM1 null is not only associated with an increased risk of cancer development, but also an increased level of markers of the biological active dose and early markers of effect. Additional studies on the role of genetic variants of xenobiotica metabolizing enzymes and combinations thereof at relevant low levels of exposure are important in order to establish guidance values for toxic compounds.
              Article 0 comments Cited 17 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): OncoTargets and Therapy
                Title: OncoTargets and therapy
                Publisher: Dove Medical Press
                ISSN (Electronic): 1178-6930
                Publication date Collection: 2015
                Publication date (Electronic): 23 July 2015
                Volume: 8
                Pages: 1835-1842
                Affiliations
                [1 ]Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
                [2 ]Department of Medical Oncology, General Hospital of The Yangtze River Shipping, Wuhan, Hubei, People’s Republic of China
                Author notes
                [*]

                These authors contributed equally to this work

                Correspondence: Zengwu Shao, Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei, People’s Republic of China, Email szwjj@ 123456medmail.com.cn
                Article
                Publisher ID: ott-8-1835
                DOI: 10.2147/OTT.S81115
                PMC ID: 4516196
                SO-VID: 8c8958a7-68d5-43d2-913b-a77618529c5c
                Copyright © © 2015 Pu et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License
                License:

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: gstp1,polymorphisms,osteosarcoma,chemotherapy,prognosis,meta-analysis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: gstp1, polymorphisms, osteosarcoma, chemotherapy, prognosis, meta-analysis

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