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Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
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Published on: October 10, 2020

The glutathione S-transferases: influence of polymorphism on cancer susceptibility

R C Strange1, A A Fryer

  • 1Clinical Biochemistry Research Group, School of Postgraduate Medicine, Keele University, North Staffordshire Hospital, Stoke-on-Trent, United Kingdom.

IARC Scientific Publications
|September 24, 1999
PubMed

Insights

Glutathione S-transferase (GST) gene polymorphisms may influence cancer risk by affecting detoxification. However, evidence linking GST variants to cancer susceptibility, particularly smoking-related cancers, remains inconclusive.

Area of Science:

  • Biochemistry
  • Genetics
  • Oncology

Background:

  • The glutathione S-transferase (GST) supergene family provides cellular defense against harmful chemicals, including carcinogens.
  • Polymorphisms within GST genes suggest that variations in detoxification efficiency could impact cancer susceptibility.
  • Specific GST loci, such as GSTM1, GSTT1, GSTM3, and GSTP1, are investigated for their roles in cancer risk.

Purpose of the Study:

  • To review the influence of glutathione S-transferase polymorphisms on the risk of various cancers.
  • To explore the potential role of GST enzymes in detoxifying products of ultraviolet radiation-induced oxidative stress, particularly in basal cell carcinoma.
  • To discuss current knowledge on GST gene polymorphisms, substrates, and the challenges in epidemiological data interpretation.

Main Methods:

  • Review of existing literature on glutathione S-transferase gene polymorphisms and cancer risk.
  • Analysis of epidemiological data, including case-control studies for lung, bladder, and colon cancers.
  • Examination of associations between GST genotypes and basal cell carcinoma, considering tumor characteristics.

Main Results:

  • Conflicting findings exist regarding the association between GSTM1 and GSTT1 genotypes and the risk of lung, bladder, and colon cancers.
  • Evidence for the role of GST polymorphisms in mediating smoking-related cancer risk remains largely unproven.
  • Associations between GST enzymes and basal cell carcinoma suggest a role in detoxifying UV-induced oxidative stress products.

Conclusions:

  • The precise function of glutathione S-transferase enzymes and the impact of their polymorphisms on cancer risk require further investigation.
  • Epidemiological data on GST polymorphisms and cancer susceptibility are often contradictory, highlighting the complexity of this gene family's role.
  • GST enzymes may play a significant role in protecting against UV-induced oxidative damage, warranting further study in skin carcinogenesis.

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