Glutathione S-transferase P1 gene rs4147581 polymorphism predicts overall survival of patients with hepatocellular carcinoma: evidence from an enlarged study
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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.
KeywordsGlutathione S-transferase Single nucleotide polymorphism (SNP) Hepatocellular carcinoma Prognosis
This study was supported by the National Natural Science Foundation of China (Grant Nos. 81201549, 81272644, 81402022, and 81472247) and the Project of Innovative Research Team for Key Science and Technology in Shaanxi province (Grant No. 2013KCJ-23).
Conflicts of interest
There is no competing financial interest among the authors.
Yuelang Zhang and Xiaoqun Dong were responsible for experimental design and supervised the study. Zhixin Wang, Kai Qu, Zichao Huang, and Susun Liu developed methodology. Zhixin Wang, Kai Qu, Sinan Liu, Hulin Chang, Xinsen Xu, Ting Lin, Yamin Liu, and Chang Liu carried out the experiments. Zhixin Wang, Kai Qu, and Wenquan Niu performed data analysis and prepared the figures and tables. Zhixin Wang, Kai Qu, Wenquan Niu, and Xiaoqun Dong wrote, reviewed, and revised the manuscript.
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