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Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression

BACKGROUND: Glutathione S-transferase mu 3 (GSTM3) has been proven to be downregulated in renal cell carcinoma (RCC). We aimed to characterise the role of GSTM3 and its genetic predisposition on the occurrence and postoperative prognosis of RCC. METHODS: The effect of GSTM3 on RCC aggressiveness was...

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Autores principales: Tan, X, Wang, Y, Han, Y, Chang, W, Su, T, Hou, J, Xu, D, Yu, Y, Ma, W, Thompson, T C, Cao, G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859948/
https://www.ncbi.nlm.nih.gov/pubmed/24157827
http://dx.doi.org/10.1038/bjc.2013.669
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author Tan, X
Wang, Y
Han, Y
Chang, W
Su, T
Hou, J
Xu, D
Yu, Y
Ma, W
Thompson, T C
Cao, G
author_facet Tan, X
Wang, Y
Han, Y
Chang, W
Su, T
Hou, J
Xu, D
Yu, Y
Ma, W
Thompson, T C
Cao, G
author_sort Tan, X
collection PubMed
description BACKGROUND: Glutathione S-transferase mu 3 (GSTM3) has been proven to be downregulated in renal cell carcinoma (RCC). We aimed to characterise the role of GSTM3 and its genetic predisposition on the occurrence and postoperative prognosis of RCC. METHODS: The effect of GSTM3 on RCC aggressiveness was examined using transfection and silencing methods. Glutathione S-transferase mu 3 expression in renal tissues was examined by immunohistochemistry. The associations of rs1332018 (A-63C) and rs7483 (V224I) polymorphisms with RCC risk were examined using 400 RCC patients and 802 healthy controls. The factors contributing to postoperative disease-specific survival of RCC patients were evaluated using the Cox proportional hazard model. RESULTS: Glutathione S-transferase mu 3 silencing increased the invasion and anchorage-independent growth of RCC cell lines. rs1332018 (AC+CC vs AA), which correlated with low expression of GSTM3 in kidney, was associated with RCC risk (odds ratio, 1.446; 95% confidence interval (CI), 1.111–1.882). rs1332018 variants and low GSTM3 expression significantly predicted unfavourable postoperative survivals of RCC patients (P<0.05). rs1332018 variants independently predicted a poor prognosis (hazard ratio, 2.119; 95% CI, 1.043–4.307). CONCLUSION: Glutathione S-transferase mu 3 may function as a tumour suppressor in RCC. rs1332018 genetic variants predispose the host to downregulating GSTM3 expression in kidney, facilitate carcinogenesis, and predict an unfavourable postoperative prognosis of RCC.
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spelling pubmed-38599482014-12-10 Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression Tan, X Wang, Y Han, Y Chang, W Su, T Hou, J Xu, D Yu, Y Ma, W Thompson, T C Cao, G Br J Cancer Genetics and Genomics BACKGROUND: Glutathione S-transferase mu 3 (GSTM3) has been proven to be downregulated in renal cell carcinoma (RCC). We aimed to characterise the role of GSTM3 and its genetic predisposition on the occurrence and postoperative prognosis of RCC. METHODS: The effect of GSTM3 on RCC aggressiveness was examined using transfection and silencing methods. Glutathione S-transferase mu 3 expression in renal tissues was examined by immunohistochemistry. The associations of rs1332018 (A-63C) and rs7483 (V224I) polymorphisms with RCC risk were examined using 400 RCC patients and 802 healthy controls. The factors contributing to postoperative disease-specific survival of RCC patients were evaluated using the Cox proportional hazard model. RESULTS: Glutathione S-transferase mu 3 silencing increased the invasion and anchorage-independent growth of RCC cell lines. rs1332018 (AC+CC vs AA), which correlated with low expression of GSTM3 in kidney, was associated with RCC risk (odds ratio, 1.446; 95% confidence interval (CI), 1.111–1.882). rs1332018 variants and low GSTM3 expression significantly predicted unfavourable postoperative survivals of RCC patients (P<0.05). rs1332018 variants independently predicted a poor prognosis (hazard ratio, 2.119; 95% CI, 1.043–4.307). CONCLUSION: Glutathione S-transferase mu 3 may function as a tumour suppressor in RCC. rs1332018 genetic variants predispose the host to downregulating GSTM3 expression in kidney, facilitate carcinogenesis, and predict an unfavourable postoperative prognosis of RCC. Nature Publishing Group 2013-12-10 2013-10-24 /pmc/articles/PMC3859948/ /pubmed/24157827 http://dx.doi.org/10.1038/bjc.2013.669 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Genetics and Genomics
Tan, X
Wang, Y
Han, Y
Chang, W
Su, T
Hou, J
Xu, D
Yu, Y
Ma, W
Thompson, T C
Cao, G
Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression
title Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression
title_full Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression
title_fullStr Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression
title_full_unstemmed Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression
title_short Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression
title_sort genetic variation in the gstm3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression
topic Genetics and Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859948/
https://www.ncbi.nlm.nih.gov/pubmed/24157827
http://dx.doi.org/10.1038/bjc.2013.669
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