Analysis of the glutathione S-transferase genes polymorphisms in the risk and prognosis of renal cell carcinomas. Case-control and meta-analysis

Aiysha Abid; Sadia Ajaz; Abdul Rafay Khan; Fatima Zehra; Asad Shahzad Hasan; Gauhar Sultan; Rehan Mohsin; Altaf Hashmi; Najeeb Niamatullah; Syed Adib-Ul-Hasan Rizvi; Syed Qasim Mehdi; Shagufta Khaliq

doi:10.1016/j.urolonc.2016.04.005

Analysis of the glutathione S-transferase genes polymorphisms in the risk and prognosis of renal cell carcinomas. Case-control and meta-analysis

Urol Oncol. 2016 Sep;34(9):419.e1-419.e12. doi: 10.1016/j.urolonc.2016.04.005. Epub 2016 May 13.

Affiliations

¹ Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan. Electronic address: aiyshaabid@gmail.com.
² Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan.
³ Department of Oncology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan.
⁴ Department of Urology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan.
⁵ Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan; Department of Human Genetics, University of Health Sciences (UHS), Lahore, Pakistan.

PMID: 27185341
DOI: 10.1016/j.urolonc.2016.04.005

Abstract

Background: The Glutathione S-transferases (GSTs) genes deletion polymorphisms have been associated with the progression of several cancers. The association studies between the 2 GSTs (GSTM1 and GSTT1) null polymorphisms with the susceptibility to renal cell carcinoma (RCC) have been inconclusive. Therefore, with the inclusion of our own data, we performed a comprehensive meta-analysis to assess the association between these 2 polymorphisms and the risk of RCC.

Methods: A systematic literature search was carried out for studies published in the PubMed, EMBASE, Cochrane library, and Google Scholar from 1997 to December 2014. Results were stated as pooled odds ratios (ORs) for nonparametric data after heterogeneity analysis with 95% CI using fixed effect or random effect model.

Results: We systematically selected 13 relevant studies after thorough searches from the databases. Data showed no association between the GSTM1 and the GSTT1 null genotypes and the risk of RCC (OR = 1.01; CI: 0.92-1.11; P = 0.89 for GSTM1 and OR = 1.14; CI: 0.91-1.42; P = 0.25 for GSTT1). No association was found when the data were stratified according to the geographical/ethnic basis, source of control, and the risk factor evaluation. Subgroup analysis of occupational exposure to pesticides showed an inverse association of the active genotypes of both GSTM1 and GSTT1 polymorphisms with the exposed group of RCC (P<0.00001 and P<0.00001, respectively). The combined null genotype of the GSTM1/GSTT1 significantly increased the susceptibility to RCC by 1.4-fold (P = 0.001). This association remained significant for the Asian populations in subgroup analysis (OR = 1.8; CI: 1.30-2.49; P = 0.0004).

Conclusion: In conclusion, this meta-analysis suggests that the 2 GSTs deletion polymorphisms independently have no association with the risk of RCC. However, combination of both deletions increases the risk of developing the RCC.

Keywords: Glutathione S-transferase genes Polymorphisms; Meta-analysis; Renal cell carcinoma.

Publication types

Meta-Analysis

MeSH terms

Carcinoma, Renal Cell / genetics*
Case-Control Studies
Genetic Predisposition to Disease
Glutathione Transferase / genetics*
Humans
Kidney Neoplasms / genetics*
Polymorphism, Genetic
Prognosis

Substances

glutathione S-transferase T1
Glutathione Transferase
glutathione S-transferase M1