Association of GST genetic polymorphisms with the susceptibility to hepatocellular carcinoma (HCC) in Chinese population evaluated by an updated systematic meta-analysis
Authors: Liangliang Chen
Jinshun Zhao
Kui Liu
Lu Zhang
Hongbo Shi
Baobo Zou
Ruth Magaye
Xialu Lin
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Glutathione S-transferase Mu-1; Glutathione S-transferase theta-1; genetic polymorphisms; hepatocellular carcinoma; Chinese population
Affiliations: Department of Preventative Medicine and Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People's Republic of China.

Abstract:  Background: Due to the possible involvement of Glutathione S-transferase Mu-1 (GSTM1) and Glutathione S-transferase theta-1 (GSTT1) in the detoxification of environmental carcinogens, environmental toxins, and oxidative stress products, genetic polymorphisms of these two genes may play important roles in the susceptibility of human being to hepatocellular carcinoma. However, the existing research results are not conclusive. Methods: A systematic literature search using databases (PubMed, Scopus, Embase, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Wanfang Data, etc.) for the eligible studies meeting the inclusion criteria including case-control studies or cohort studies is evaluated using an updated systematic meta-analysis. Results: Significant increase in the risk of HCC in the Chinese population is found in GSTM1 null genotype (OR = 1.47, 95% CI: 1.21 to 1.79, P&lt;0.001) and GSTT1 null genotype (OR = 1.38, 95% CI: 1.14 to 1.65, P&lt;0.001). Analysis using the random-effects model found an increased risk of HCC in GSTM1-GSTT1 dual null population (OR = 1.79, 95% CI: 1.26 to 2.53, P&lt;0.001). In addition, subgroup analyses showed a significant increase in the association of GST genetic polymorphisms (GSTM1, GSTT1, and GSTM1-GSTT1) with HCC in southeast and central China mainland. However, available data collected by this study fail to show an association between GST genetic polymorphisms and HCC in people from the Taiwan region (for GSTM1: OR = 0.78, 95% CI: 0.60 to 1.01, P = 0.06; for GSTT1: OR = 0.94, 95% CI: 0.78 to 1.14, P = 0.546; for GSTM1-GSTT1: OR = 1.04, 95% CI: 0.81 to 1.32, P = 0.77). Sensitivity analysis and publication bias diagnostics confirmed the reliability and stability of this meta-analysis. Conclusions: Our results indicate that both GSTM1 and GSTT1 null genotypes are associated with an increased HCC risk in Chinese population. Peoples with dual null genotypes of GSTM1-GSTT1 are more susceptible to developing HCC. In conclusion, GST genetic polymorphisms play vital roles in the development of HCC in the Chinese population. 

Retracted: No

PubPeer comments:
 The method employed for the evaluation of publication bias in this meta-analysis is incorrectly referred to as  Beggar s funnel plot in the article (Statistical Analysis section within the Methods, Potential Publication Bias section within the Results, legend of Figure 6, and Discussion section). The method should have been cited as Begg s funnel plot. The authors apologize for this error. Citation: Liu K, Zhang L, Lin X, Chen L, Shi H, Magaye R, et al. (2014) Correction: Association of GST Genetic Polymorphisms with the Susceptibility to Hepatocellular Carcinoma (HCC) in Chinese Population Evaluated by an Updated Systematic Meta-Analysis. PLoS ONE 9(1): 10.1371 annotation 13ee8778-996e-4649-af2e-4390378c2493. https: doi.org 10.1371 annotation 13ee8778-996e-4649-af2e-4390378c2493 Published: January 29, 2014 *** Prior to the correction, this paper included a reference to u201cBeggers funnel plot,u201d (alt spelling: Beggeru2019s) a non-existent test discussed in the 2014 Scientific American (SA) article at the link below, which author Charles Seife uses as a keyword to identify papers produced by u201cpaper mills.u201d I am posting this comment on a number of papers Iu2019ve located that included the u201cBeggers funnel plotu201d term so thereu2019s a PubPeer record for the institutions and authors involved. If any author wishes to comment, please feel free to do so here. Below is information from the SA article. https: www.scientificamerican.com article for-sale-your-name-here-in-a-prestigious-science-journal For Sale: u201cYour Name Hereu201d in a Prestigious Science Journal *An investigation into some scientific papers finds worrying irregularities* Two relevant excerpts: u201c u2018Beggers funnel plotu2019 is particularly revealing. **There is no such thing as a Beggers funnel plot.**  It doesn t exist. That s the point, says Guillaume Filion, a biologist at the Center for Genomic Regulation in Barcelona, Spain (pdf). A statistician named Colin Begg and another statistician named Matthias Egger each invented tests and tools to look for biases that creep into meta-analyses.  Begger s funnel plot appears to be an accidental hybrid of the two names.u201d [emphasis added] Filion spotted the proliferation of  Begger s tests by accident. While looking for trends in medical journal articles, he found papers that had almost identical titles, similar choices in graphics and the same quirky errors, such as  Begger s funnel plot. He reckons that the papers came from the same source, even though they are ostensibly written by different groups of authors.  It s difficult to imagine that 28 people independently would invent the name of a statistical test, Filion says. u2018So that s why we were very shocked.u2019 u201c ,