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Published in: Tumor Biology 1/2016

01-01-2016 | Original Article

Glutathione S-transferase P1 gene rs4147581 polymorphism predicts overall survival of patients with hepatocellular carcinoma: evidence from an enlarged study

Authors: Zhixin Wang, Kai Qu, Wenquan Niu, Ting Lin, Xinsen Xu, Zichao Huang, Sushun Liu, Sinan Liu, Hulin Chang, Yamin Liu, Xiaoqun Dong, Chang Liu, Yuelang Zhang

Published in: Tumor Biology | Issue 1/2016

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Abstract

As the most important detoxifying enzymes in liver, glutathione S-transferases (GSTs) can protect hepatocytes against carcinogens. We conducted a large cohort study to investigate the prognostic value of single nucleotide polymorphisms (SNPs) in seven encoding genes of GSTs for hepatocellular carcinoma (HCC). Twelve SNPs were genotyped and correlated with overall survival in 469 HCC patients. The median follow-up time of all patients was 21 (range 3–60) months, and the median survival time was 22 months. By the end of the study, 135 (28.8 %) patients were alive. Only rs4147581 in GSTP1 gene exhibited a significant association with survival of HCC patients (P = 0.006), with its mutant allele bearing a significantly lower risk of death (hazard ratio, 0.71; 95 % confidence interval 0.53–0.90), compared with the homozygous wide-type. A longer median survival time in patients with rs4147581 mutant allele was noticed than those homozygous wide-type (P = 0.03), and there was a marked adverse effect on survival conferred by smoking exposure in these patients. Conclusively, our findings provide supporting evidence for a contributory role of GSTP1 rs4147581 polymorphism in predicting the prognosis of HCC.
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Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
3.
go back to reference Gross-Steinmeyer K, Eaton DL. Dietary modulation of the biotransformation and genotoxicity of aflatoxin b(1). Toxicology. 2012;299:69–79.CrossRefPubMed Gross-Steinmeyer K, Eaton DL. Dietary modulation of the biotransformation and genotoxicity of aflatoxin b(1). Toxicology. 2012;299:69–79.CrossRefPubMed
4.
go back to reference Chasseaud LF. The role of glutathione and glutathione S-transferases in the metabolism of chemical carcinogens and other electrophilic agents. Adv Cancer Res. 1979;29:175–274.CrossRefPubMed Chasseaud LF. The role of glutathione and glutathione S-transferases in the metabolism of chemical carcinogens and other electrophilic agents. Adv Cancer Res. 1979;29:175–274.CrossRefPubMed
5.
go back to reference Lee WH, Morton RA, Epstein JI, Brooks JD, Campbell PA, Bova GS, et al. Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proc Natl Acad Sci U S A. 1994;91:11733–7.CrossRefPubMedPubMedCentral Lee WH, Morton RA, Epstein JI, Brooks JD, Campbell PA, Bova GS, et al. Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proc Natl Acad Sci U S A. 1994;91:11733–7.CrossRefPubMedPubMedCentral
6.
go back to reference Niu D, Zhang J, Ren Y, Feng H, Chen WN. Hbx genotype d represses gstp1 expression and increases the oxidative level and apoptosis in hepg2 cells. Mol Oncol. 2009;3:67–76.CrossRefPubMed Niu D, Zhang J, Ren Y, Feng H, Chen WN. Hbx genotype d represses gstp1 expression and increases the oxidative level and apoptosis in hepg2 cells. Mol Oncol. 2009;3:67–76.CrossRefPubMed
7.
go back to reference Zhang YJ, Chen Y, Ahsan H, Lunn RM, Chen SY, Lee PH, et al. Silencing of glutathione S-transferase p1 by promoter hypermethylation and its relationship to environmental chemical carcinogens in hepatocellular carcinoma. Cancer Lett. 2005;221:135–43.CrossRefPubMed Zhang YJ, Chen Y, Ahsan H, Lunn RM, Chen SY, Lee PH, et al. Silencing of glutathione S-transferase p1 by promoter hypermethylation and its relationship to environmental chemical carcinogens in hepatocellular carcinoma. Cancer Lett. 2005;221:135–43.CrossRefPubMed
8.
go back to reference Daniel V. Glutathione S-transferases: gene structure and regulation of expression. Crit Rev Biochem Mol Biol. 1993;28:173–207.CrossRefPubMed Daniel V. Glutathione S-transferases: gene structure and regulation of expression. Crit Rev Biochem Mol Biol. 1993;28:173–207.CrossRefPubMed
9.
go back to reference Curran JE, Weinstein SR, Griffiths LR. Polymorphisms of glutathione S-transferase genes (gstm1, gstp1 and gstt1) and breast cancer susceptibility. Cancer Lett. 2000;153:113–20.CrossRefPubMed Curran JE, Weinstein SR, Griffiths LR. Polymorphisms of glutathione S-transferase genes (gstm1, gstp1 and gstt1) and breast cancer susceptibility. Cancer Lett. 2000;153:113–20.CrossRefPubMed
10.
go back to reference Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA. Human glutathione S-transferase p1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis. 1998;19:275–80.CrossRefPubMed Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA. Human glutathione S-transferase p1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis. 1998;19:275–80.CrossRefPubMed
11.
go back to reference Stoehlmacher J, Park DJ, Zhang W, Groshen S, Tsao-Wei DD, Yu MC, et al. Association between glutathione S-transferase p1, t1, and m1 genetic polymorphism and survival of patients with metastatic colorectal cancer. J Natl Cancer Inst. 2002;94:936–42.CrossRefPubMed Stoehlmacher J, Park DJ, Zhang W, Groshen S, Tsao-Wei DD, Yu MC, et al. Association between glutathione S-transferase p1, t1, and m1 genetic polymorphism and survival of patients with metastatic colorectal cancer. J Natl Cancer Inst. 2002;94:936–42.CrossRefPubMed
12.
go back to reference Howells RE, Dhar KK, Hoban PR, Jones PW, Fryer AA, Redman CW, et al. Association between glutathione-S-transferase gstp1 genotypes, gstp1 over-expression, and outcome in epithelial ovarian cancer. Int J Gynecol Cancer. 2004;14:242–50.CrossRefPubMed Howells RE, Dhar KK, Hoban PR, Jones PW, Fryer AA, Redman CW, et al. Association between glutathione-S-transferase gstp1 genotypes, gstp1 over-expression, and outcome in epithelial ovarian cancer. Int J Gynecol Cancer. 2004;14:242–50.CrossRefPubMed
13.
go back to reference Okcu MF, Selvan M, Wang LE, Stout L, Erana R, Airewele G, et al. Glutathione S-transferase polymorphisms and survival in primary malignant glioma. Clin Cancer Res. 2004;10:2618–25.CrossRefPubMed Okcu MF, Selvan M, Wang LE, Stout L, Erana R, Airewele G, et al. Glutathione S-transferase polymorphisms and survival in primary malignant glioma. Clin Cancer Res. 2004;10:2618–25.CrossRefPubMed
14.
go back to reference Wenzlaff AS, Cote ML, Bock CH, Land SJ, Schwartz AG. Gstm1, gstt1 and gstp1 polymorphisms, environmental tobacco smoke exposure and risk of lung cancer among never smokers: a population-based study. Carcinogenesis. 2005;26:395–401.CrossRefPubMed Wenzlaff AS, Cote ML, Bock CH, Land SJ, Schwartz AG. Gstm1, gstt1 and gstp1 polymorphisms, environmental tobacco smoke exposure and risk of lung cancer among never smokers: a population-based study. Carcinogenesis. 2005;26:395–401.CrossRefPubMed
15.
go back to reference White DL, Li D, Nurgalieva Z, El-Serag HB. Genetic variants of glutathione S-transferase as possible risk factors for hepatocellular carcinoma: a huge systematic review and meta-analysis. Am J Epidemiol. 2008;167:377–89.CrossRefPubMed White DL, Li D, Nurgalieva Z, El-Serag HB. Genetic variants of glutathione S-transferase as possible risk factors for hepatocellular carcinoma: a huge systematic review and meta-analysis. Am J Epidemiol. 2008;167:377–89.CrossRefPubMed
16.
go back to reference Chen YL, Tseng HS, Kuo WH, Yang SF, Chen DR, Tsai HT. Glutathione S-transferase p1 (gstp1) gene polymorphism increases age-related susceptibility to hepatocellular carcinoma. BMC Med Genet. 2010;11:46.CrossRefPubMedPubMedCentral Chen YL, Tseng HS, Kuo WH, Yang SF, Chen DR, Tsai HT. Glutathione S-transferase p1 (gstp1) gene polymorphism increases age-related susceptibility to hepatocellular carcinoma. BMC Med Genet. 2010;11:46.CrossRefPubMedPubMedCentral
17.
go back to reference Kilburn L, Okcu MF, Wang T, Cao Y, Renfro-Spelman A, Aldape KD, et al. Glutathione S-transferase polymorphisms are associated with survival in anaplastic glioma patients. Cancer. 2010;116:2242–9.PubMedPubMedCentral Kilburn L, Okcu MF, Wang T, Cao Y, Renfro-Spelman A, Aldape KD, et al. Glutathione S-transferase polymorphisms are associated with survival in anaplastic glioma patients. Cancer. 2010;116:2242–9.PubMedPubMedCentral
18.
go back to reference Sergentanis TN, Economopoulos KP. Gstt1 and gstp1 polymorphisms and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2010;121:195–202.CrossRefPubMed Sergentanis TN, Economopoulos KP. Gstt1 and gstp1 polymorphisms and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2010;121:195–202.CrossRefPubMed
19.
go back to reference Xu Z, Zhu H, Luk JM, Wu D, Gu D, Gong W, et al. Clinical significance of sod2 and gstp1 gene polymorphisms in Chinese patients with gastric cancer. Cancer. 2012;118:5489–96.CrossRefPubMed Xu Z, Zhu H, Luk JM, Wu D, Gu D, Gong W, et al. Clinical significance of sod2 and gstp1 gene polymorphisms in Chinese patients with gastric cancer. Cancer. 2012;118:5489–96.CrossRefPubMed
20.
go back to reference Qu K, Liu SS, Wang ZX, Huang ZC, Liu SN, Chang HL, et al. Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients. World J Gastroenterol. 2015;21:4310–22.CrossRefPubMedPubMedCentral Qu K, Liu SS, Wang ZX, Huang ZC, Liu SN, Chang HL, et al. Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients. World J Gastroenterol. 2015;21:4310–22.CrossRefPubMedPubMedCentral
21.
go back to reference Wang Z, Qu K, Huang Z, Xu X, Zhang J, Zhang L, et al. Glutathione S-transferase o2 gene rs157077 polymorphism predicts response to transarterial chemoembolization in hepatocellular carcinoma. 2015. Wang Z, Qu K, Huang Z, Xu X, Zhang J, Zhang L, et al. Glutathione S-transferase o2 gene rs157077 polymorphism predicts response to transarterial chemoembolization in hepatocellular carcinoma. 2015.
22.
go back to reference Zhao Y, Wang F, Shan S, Zhao Y, Qiu X, Li X, et al. Genetic polymorphism of p53, but not gstp1, is association with susceptibility to esophageal cancer risk—a meta-analysis. Int J Med Sci. 2010;7:300–8.CrossRefPubMedPubMedCentral Zhao Y, Wang F, Shan S, Zhao Y, Qiu X, Li X, et al. Genetic polymorphism of p53, but not gstp1, is association with susceptibility to esophageal cancer risk—a meta-analysis. Int J Med Sci. 2010;7:300–8.CrossRefPubMedPubMedCentral
23.
go back to reference Yang G, Shu XO, Ruan ZX, Cai QY, Jin F, Gao YT, et al. Genetic polymorphisms in glutathione-S-transferase genes (gstm1, gstt1, gstp1) and survival after chemotherapy for invasive breast carcinoma. Cancer. 2005;103:52–8.CrossRefPubMed Yang G, Shu XO, Ruan ZX, Cai QY, Jin F, Gao YT, et al. Genetic polymorphisms in glutathione-S-transferase genes (gstm1, gstt1, gstp1) and survival after chemotherapy for invasive breast carcinoma. Cancer. 2005;103:52–8.CrossRefPubMed
24.
go back to reference Agalliu I, Lin DW, Salinas CA, Feng Z, Stanford JL. Polymorphisms in the glutathione S-transferase m1, t1, and p1 genes and prostate cancer prognosis. Prostate. 2006;66:1535–41.CrossRefPubMed Agalliu I, Lin DW, Salinas CA, Feng Z, Stanford JL. Polymorphisms in the glutathione S-transferase m1, t1, and p1 genes and prostate cancer prognosis. Prostate. 2006;66:1535–41.CrossRefPubMed
25.
go back to reference Nagle CM, Chenevix-Trench G, Spurdle AB, Webb PM. The role of glutathione-S-transferase polymorphisms in ovarian cancer survival. Eur J Cancer. 2007;43:283–90.CrossRefPubMed Nagle CM, Chenevix-Trench G, Spurdle AB, Webb PM. The role of glutathione-S-transferase polymorphisms in ovarian cancer survival. Eur J Cancer. 2007;43:283–90.CrossRefPubMed
26.
go back to reference Breton CV, Byun HM, Wenten M, Pan F, Yang A, Gilliland FD. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med. 2009;180:462–7.CrossRefPubMedPubMedCentral Breton CV, Byun HM, Wenten M, Pan F, Yang A, Gilliland FD. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med. 2009;180:462–7.CrossRefPubMedPubMedCentral
27.
go back to reference Zhong S, Tang MW, Yeo W, Liu C, Lo YM, Johnson PJ. Silencing of gstp1 gene by cpg island DNA hypermethylation in hbv-associated hepatocellular carcinomas. Clin Cancer Res. 2002;8:1087–92.PubMed Zhong S, Tang MW, Yeo W, Liu C, Lo YM, Johnson PJ. Silencing of gstp1 gene by cpg island DNA hypermethylation in hbv-associated hepatocellular carcinomas. Clin Cancer Res. 2002;8:1087–92.PubMed
28.
go back to reference Ding S, Gong BD, Yu J, Gu J, Zhang HY, Shang ZB, et al. Methylation profile of the promoter cpg islands of 14 “drug-resistance” genes in hepatocellular carcinoma. World J Gastroenterol. 2004;10:3433–40.CrossRefPubMedPubMedCentral Ding S, Gong BD, Yu J, Gu J, Zhang HY, Shang ZB, et al. Methylation profile of the promoter cpg islands of 14 “drug-resistance” genes in hepatocellular carcinoma. World J Gastroenterol. 2004;10:3433–40.CrossRefPubMedPubMedCentral
29.
go back to reference Munaka M, Kohshi K, Kawamoto T, Takasawa S, Nagata N, Itoh H, et al. Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma. J Cancer Res Clin Oncol. 2003;129:355–60.CrossRefPubMed Munaka M, Kohshi K, Kawamoto T, Takasawa S, Nagata N, Itoh H, et al. Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma. J Cancer Res Clin Oncol. 2003;129:355–60.CrossRefPubMed
Metadata
Title
Glutathione S-transferase P1 gene rs4147581 polymorphism predicts overall survival of patients with hepatocellular carcinoma: evidence from an enlarged study
Authors
Zhixin Wang
Kai Qu
Wenquan Niu
Ting Lin
Xinsen Xu
Zichao Huang
Sushun Liu
Sinan Liu
Hulin Chang
Yamin Liu
Xiaoqun Dong
Chang Liu
Yuelang Zhang
Publication date
01-01-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 1/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3871-7

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