GSTM1

GSTM1 Full Name

glutathione S-transferase mu 1

GSTM1 Introduction

GSTM1 encodes a cytosolic enzyme of the mu class of glutathione S-transferases, a family of phase II detoxification enzymes that catalyze the conjugation of glutathione to electrophilic compounds, facilitating their elimination from the body. The GSTM1 protein is expressed in multiple tissues, including the liver, lung, brain, kidney, and erythrocytes, where it metabolizes a broad spectrum of carcinogenic substrates, including epoxides of polycyclic aromatic hydrocarbons, alkyl halides, and chemotherapeutic agents. A distinctive feature of GSTM1 is the high prevalence of a homozygous gene deletion (the GSTM1 null genotype) in human populations, occurring in approximately 40–50% of individuals of European descent and at varying frequencies across other ethnic groups. Individuals carrying the GSTM1 null genotype completely lack functional GSTM1 enzyme, resulting in impaired capacity to detoxify certain carcinogens and environmental toxins, which has been proposed as a genetic basis for interindividual variability in cancer susceptibility.

Figure 1. The GSTM locus evolution. (Source: Saitou M, et al. 2018)

The GSTM1 null genotype has been the subject of extensive epidemiological investigation as a candidate modifier of cancer risk. Large-scale meta-analyses have consistently demonstrated that the GSTM1 null genotype is associated with modest but statistically significant increases in the risk of lung cancer, bladder cancer, oral cancer, and cervical cancer, particularly among smokers exposed to tobacco-derived carcinogens. Beyond oncology, GSTM1 deficiency has been linked to enhanced susceptibility to inflammatory and oxidative stress-related conditions, including asthma, chronic obstructive pulmonary disease, and cardiovascular disease. In the context of chemotherapy, the GSTM1 null genotype may influence drug pharmacokinetics and treatment response, though findings have been inconsistent across studies. The GSTM1 null polymorphism frequently coexists with a similar deletion in the GSTT1 gene, and individuals with dual null genotypes exhibit compounded detoxification deficits, further amplifying disease risk. These findings highlight the importance of GST genotyping in personalized medicine and risk assessment for environmentally associated diseases.

Alternate Names for GSTM1

GSTM1; glutathione S-transferase mu 1; glutathione S transferase M1 , GST1; glutathione S-transferase Mu 1; H B; MU; Glutathione S transferase mu; Glutathione S-transferase Mu 1; GST class mu 1; GST class Mu

• 1. Zhao Y, et al. Individual and combined effects of the GSTM1, GSTT1, and GSTP1 polymorphisms on leukemia risk: An updated meta-analysis. Front Genet. 2022 Oct 31;13:976673.
  2. Saitou M, et al. Complex evolution of the GSTM gene family involves sharing of GSTM1 deletion polymorphism in humans and chimpanzees. BMC Genomics. 2018 Apr 25;19(1):293.