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Gene Review

GSTM1  -  glutathione S-transferase mu 1

Homo sapiens

Synonyms: GST HB subunit 4, GST class-mu 1, GST1, GSTM1-1, GSTM1a-1a, ...

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Disease relevance of GSTM1


Psychiatry related information on GSTM1


High impact information on GSTM1


Chemical compound and disease context of GSTM1


Biological context of GSTM1


Anatomical context of GSTM1

  • To investigate a relationship between genetically determined individual predispositions and mutations of target genes in the early stage of lung carcinogenesis, we examined p53 mutations in relation to germ line polymorphisms of the CYP1A1 and GSTM1 genes, using surgical specimens of 148 non-small cell lung cancer patients who were smokers [19].
  • These results imply that the GSTM1 null genotype has a weak correlation, but another 4 genetic polymorphisms are unlikely to be associated, with oral cavity cancer among Japanese [20].
  • A higher proportion of the patients with positive lymph node status at the time of diagnosis had a combined GSTM1 null/GSTT1 null genotype (P = 0.05) [21].
  • The relative levels of expression of GSTM1 and GSTM3 in brain cytosols were determined after resolution of these enzymes using chromatofocusing [22].
  • Cells isolated from colon tissue were identified to be colonocytes and colon fibroblasts, both of which also expressed substantial levels of GSTM1 and GSTM2 [23].

Associations of GSTM1 with chemical compounds

  • CYP2D6 and CYP2E1 genotypes are associated with higher 7-methyl-dGMP levels, while the GSTM1 null genotype is associated with higher numbers of PAH-dGMP adducts [17].
  • CYP1A1 and GSTM1 polymorphisms affect urinary 1-hydroxypyrene levels after PAH exposure [24].
  • Overall, statistically significant interactions in predicting DNA adduct levels were observed between the GSTM1-null genotype and consumption of leafy vegetables (P = 0.01), white meat (P = 0.04), and intake of vitamin C (P = 0.04), vitamin E (P = 0.05) and beta-carotene (P = 0.02) [25].
  • In individuals not occupationally exposed to PAHs GSTM1 and smoking seem to influence the urinary concentration of 2-naphthol [26].
  • The GSTM1 genotype was clearly the most significant parameter explaining the variance in urinary PHEMA excretion (6-fold lower in GSTM1 null subjects; P < 0.0001) so that systematic GSTM1 genotyping should be recommended routinely for a correct interpretation of PHEMA urinary levels [27].

Physical interactions of GSTM1

  • Based on adjustment by age, gender and smoking history, the MPO GA interacted with the presence of GSTM1 and GSTT1 genotypes to significantly reduce the risk (OR = 0.17, 95% CI = 0.03-0.98) [28].

Enzymatic interactions of GSTM1

  • Earlier clinical manifestations and death before the age of 5 years are typical for GSTM1-deleted CF patients [29].

Regulatory relationships of GSTM1

  • GSTM1 deletion was quite common in both controls (49.4%) and cases (50.3%) but was not associated with risk of lung cancer alone or in combination with the MPO polymorphism [30].
  • The objective of this study was to determine whether the association between GSTM1 null/GSTTI null and survival in ovarian cancer is mediated by the influence of these genes on p53 expression [31].
  • In addition, hGST 5.8 expressed glutathione peroxidase activity toward phospholipid hydroperoxides and GSH-conjugating activity toward 9,10-epoxy stearic acid [32].
  • GSTA1-1 inhibited the formation of adducts more than 6-fold and GSTM1-1 and GSTP1-1 about 2-fold [33].
  • In this meta-analysis involving 14 GSTM1 studies with 1539 cases and 1805 controls and nine GSTT1 studies with 746 cases and 834 controls, respectively, substantial heterogeneities among studies were found [34].

Other interactions of GSTM1

  • These data underline the major importance of the CYP1A1 inducibility phenotype associated with the homozygous GSTM1 null genotype in chemically induced cancers [35].
  • NAT2 slow genotypes were also associated with CpG G:C-A:T (OR, 6.2; CI:0.7-52), whereas GSTM1 null was associated with non-CpG G:C-A:T (OR, 7.8; CI, 0.9-65) [36].
  • The potential modifying role of previously analyzed GSTM1, GSTM3, and GSTP1 genotypes was also examined [37].
  • GSTM1 AB (P = 0.016) and GSTP1 Val/Val (P = 0.046) were also associated with fewer BCC in this group [38].
  • In conclusion, low or deficient activities of two conjugating enzymes of foreign compound metabolism, GSTM1 and NAT2, may influence types of acquired mutations in p53 in bladder cancer [39].

Analytical, diagnostic and therapeutic context of GSTM1

  • In a nested case-control study, we investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer [2].
  • For GSTM1, the assignment was confirmed by Southern blot hybridization to a pair of 12.5/2.4-kb HindIII fragments [18].
  • The GSTM1 null genotype occurred at a significantly lower frequency in the AMI patient group (48%) compared both to patients with no history of AMI (59%) and to the control group (57.2%) [40].
  • Among patients treated with nitrosoureas (n = 108), those with GSTP1*A/*A and GSTM1 null genotype were 5.7 times (95% confidence interval, 0.9-37.4) more likely to experience an adverse event secondary to chemotherapy, compared with the others [41].
  • While conventional PCR assays for detection of the GSTM1 deletion differentiated homozygously deficient from hetero- or homozygously active individuals, this long PCR assay differentiates homozygously active from hetero- or homozygously deficient individuals [42].


  1. Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women. Bennett, W.P., Alavanja, M.C., Blomeke, B., Vähäkangas, K.H., Castrén, K., Welsh, J.A., Bowman, E.D., Khan, M.A., Flieder, D.B., Harris, C.C. J. Natl. Cancer Inst. (1999) [Pubmed]
  2. Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. Helzlsouer, K.J., Selmin, O., Huang, H.Y., Strickland, P.T., Hoffman, S., Alberg, A.J., Watson, M., Comstock, G.W., Bell, D. J. Natl. Cancer Inst. (1998) [Pubmed]
  3. A population-based, case-control study of polymorphisms in carcinogen-metabolizing genes, smoking, and pancreatic adenocarcinoma risk. Duell, E.J., Holly, E.A., Bracci, P.M., Liu, M., Wiencke, J.K., Kelsey, K.T. J. Natl. Cancer Inst. (2002) [Pubmed]
  4. Differential association of the codon 72 p53 and GSTM1 polymorphisms on histological subtype of non-small cell lung carcinoma. Liu, G., Miller, D.P., Zhou, W., Thurston, S.W., Fan, R., Xu, L.L., Lynch, T.J., Wain, J.C., Su, L., Christiani, D.C. Cancer Res. (2001) [Pubmed]
  5. Pharmacokinetics and toxicity of docetaxel: role of CYP3A, MDR1, and GST polymorphisms. Tran, A., Jullien, V., Alexandre, J., Rey, E., Rabillon, F., Girre, V., Dieras, V., Pons, G., Goldwasser, F., Tréluyer, J.M. Clin. Pharmacol. Ther. (2006) [Pubmed]
  6. Polymorphism in cytochrome P450 CYP2D6, CYP1A1, CYP2E1 and glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers: studies in upper aerodigestive tract cancers. Matthias, C., Bockmühl, U., Jahnke, V., Jones, P.W., Hayes, J.D., Alldersea, J., Gilford, J., Bailey, L., Bath, J., Worrall, S.F., Hand, P., Fryer, A.A., Strange, R.C. Pharmacogenetics (1998) [Pubmed]
  7. CYP1A1 Ile462Val and MPO G-463A interact to increase risk of adenocarcinoma but not squamous cell carcinoma of the lung. Larsen, J.E., Colosimo, M.L., Yang, I.A., Bowman, R., Zimmerman, P.V., Fong, K.M. Carcinogenesis (2006) [Pubmed]
  8. Polymorphisms within glutathione S-transferase genes in pediatric non-Hodgkin's lymphoma. Dieckvoss, B.O., Stanulla, M., Schrappe, M., Beier, R., Zimmermann, M., Welte, K., Reiter, A. Haematologica (2002) [Pubmed]
  9. Association analyses between polymorphisms of the phase II detoxification enzymes (GSTM1, NQO1, NQO2) and alcohol withdrawal symptoms. Okubo, T., Harada, S., Higuchi, S., Matsushita, S. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  10. Transmission of hepatitis B with resultant restriction of surgical practice. Lettau, L.A., Smith, J.D., Williams, D., Lundquist, W.D., Cruz, F., Sikes, R.K., Hadler, S.C. JAMA (1986) [Pubmed]
  11. Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility. García-Closas, M., Kelsey, K.T., Hankinson, S.E., Spiegelman, D., Springer, K., Willett, W.C., Speizer, F.E., Hunter, D.J. J. Natl. Cancer Inst. (1999) [Pubmed]
  12. Glutathione S-transferase and N-acetyltransferase genotypes and asbestos-associated pulmonary disorders. Hirvonen, A., Saarikoski, S.T., Linnainmaa, K., Koskinen, K., Husgafvel-Pursiainen, K., Mattson, K., Vainio, H. J. Natl. Cancer Inst. (1996) [Pubmed]
  13. The association of endometriosis risk and genetic polymorphisms involving dioxin detoxification enzymes: a systematic review. Guo, S.W. Eur. J. Obstet. Gynecol. Reprod. Biol. (2006) [Pubmed]
  14. Reproductive factors, glutathione S-transferase M1 and T1 genetic polymorphism and breast cancer risk. Park, S.K., Kang, D., Noh, D.Y., Lee, K.M., Kim, S.U., Choi, J.Y., Choi, I.M., Ahn, S.H., Choe, K.J., Hirvonen, A., Strickland, P.T., Yoo, K.Y. Breast Cancer Res. Treat. (2003) [Pubmed]
  15. Analysis of the EPHX1 113 polymorphism and GSTM1 homozygous null polymorphism and oral clefting associated with maternal smoking. Hartsfield, J.K., Hickman, T.A., Everett, E.T., Shaw, G.M., Lammer, E.J., Finnell, R.A. Am. J. Med. Genet. (2001) [Pubmed]
  16. Role of GSTM1, GSTP1, and GSTT1 gene polymorphism in ifosfamide metabolism affecting neurotoxicity and nephrotoxicity in children. Zielińska, E., Zubowska, M., Misiura, K. J. Pediatr. Hematol. Oncol. (2005) [Pubmed]
  17. Human lung carcinogen-DNA adduct levels mediated by genetic polymorphisms in vivo. Kato, S., Bowman, E.D., Harrington, A.M., Blomeke, B., Shields, P.G. J. Natl. Cancer Inst. (1995) [Pubmed]
  18. Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. Pearson, W.R., Vorachek, W.R., Xu, S.J., Berger, R., Hart, I., Vannais, D., Patterson, D. Am. J. Hum. Genet. (1993) [Pubmed]
  19. Association of CYP1A1 germ line polymorphisms with mutations of the p53 gene in lung cancer. Kawajiri, K., Eguchi, H., Nakachi, K., Sekiya, T., Yamamoto, M. Cancer Res. (1996) [Pubmed]
  20. Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and oral cavity cancer. Katoh, T., Kaneko, S., Kohshi, K., Munaka, M., Kitagawa, K., Kunugita, N., Ikemura, K., Kawamoto, T. Int. J. Cancer (1999) [Pubmed]
  21. Single tube multiplex polymerase chain reaction genotype analysis of GSTM1, GSTT1 and GSTP1: relation of genotypes to TP53 tumor status and clinicopathological variables in breast cancer patients. Nedelcheva Kristensen, V., Andersen, T.I., Erikstein, B., Geitvik, G., Skovlund, E., Nesland, J.M., Børresen-Dale, A.L. Pharmacogenetics (1998) [Pubmed]
  22. Allelism at the glutathione S-transferase GSTM3 locus: interactions with GSTM1 and GSTT1 as risk factors for astrocytoma. Hand, P.A., Inskip, A., Gilford, J., Alldersea, J., Elexpuru-Camiruaga, J., Hayes, J.D., Jones, P.W., Strange, R.C., Fryer, A.A. Carcinogenesis (1996) [Pubmed]
  23. Expression of glutathione S-transferases (GSTs) in human colon cells and inducibility of GSTM2 by butyrate. Ebert, M.N., Klinder, A., Peters, W.H., Schäferhenrich, A., Sendt, W., Scheele, J., Pool-Zobel, B.L. Carcinogenesis (2003) [Pubmed]
  24. CYP1A1 and GSTM1 polymorphisms affect urinary 1-hydroxypyrene levels after PAH exposure. Alexandrie, A.K., Warholm, M., Carstensen, U., Axmon, A., Hagmar, L., Levin, J.O., Ostman, C., Rannug, A. Carcinogenesis (2000) [Pubmed]
  25. The effects of diet on DNA bulky adduct levels are strongly modified by GSTM1 genotype: a study on 634 subjects. Palli, D., Masala, G., Peluso, M., Gaspari, L., Krogh, V., Munnia, A., Panico, S., Saieva, C., Tumino, R., Vineis, P., Garte, S. Carcinogenesis (2004) [Pubmed]
  26. Effects of occupation, lifestyle and genetic polymorphisms of CYP1A1, CYP2E1, GSTM1 and GSTT1 on urinary 1-hydroxypyrene and 2-naphthol concentrations. Nan, H.M., Kim, H., Lim, H.S., Choi, J.K., Kawamoto, T., Kang, J.W., Lee, C.H., Kim, Y.D., Kwon, E.H. Carcinogenesis (2001) [Pubmed]
  27. Interest of genotyping and phenotyping of drug-metabolizing enzymes for the interpretation of biological monitoring of exposure to styrene. Haufroid, V., Jakubowski, M., Janasik, B., Ligocka, D., Buchet, J.P., Bergamaschi, E., Manini, P., Mutti, A., Ghittori, S., Arand, M., Hangen, N., Oesch, F., Hirvonen, A., Lison, D. Pharmacogenetics (2002) [Pubmed]
  28. Combined effect of MPO, GSTM1 and GSTT1 polymorphisms on chromosome aberrations and lung cancer risk. Cajas-Salazar, N., Sierra-Torres, C.H., Salama, S.A., Zwischenberger, J.B., Au, W.W. International journal of hygiene and environmental health. (2003) [Pubmed]
  29. Proportion of the GSTM1 0/0 genotype in some Slavic populations and its correlation with cystic fibrosis and some multifactorial diseases. Baranov, V.S., Ivaschenko, T., Bakay, B., Aseev, M., Belotserkovskaya, R., Baranova, H., Malet, P., Perriot, J., Mouraire, P., Baskakov, V.N., Savitskyi, G.A., Gorbushin, S., Deyneka, S.I., Michnin, E., Barchuck, A., Vakharlovsky, V., Pavlov, G., Shilko, V.I., Guembitzkaya, T., Kovaleva, L. Hum. Genet. (1996) [Pubmed]
  30. Genetic polymorphism in myeloperoxidase but not GSTM1 is associated with risk of lung squamous cell carcinoma in a Chinese population. Lu, W., Xing, D., Qi, J., Tan, W., Miao, X., Lin, D. Int. J. Cancer (2002) [Pubmed]
  31. Glutathione S-transferase GSTM1 and GSTT1 genotypes in ovarian cancer: association with p53 expression and survival. Howells, R.E., Holland, T., Dhar, K.K., Redman, C.W., Hand, P., Hoban, P.R., Jones, P.W., Fryer, A.A., Strange, R.C. Int. J. Gynecol. Cancer (2001) [Pubmed]
  32. Novel human ocular glutathione S-transferases with high activity toward 4-hydroxynonenal. Singhal, S.S., Awasthi, S., Srivastava, S.K., Zimniak, P., Ansari, N.H., Awasthi, Y.C. Invest. Ophthalmol. Vis. Sci. (1995) [Pubmed]
  33. Glutathione conjugation and DNA adduct formation of dibenzo[a,l]pyrene and benzo[a]pyrene diol epoxides in V79 cells stably expressing different human glutathione transferases. Sundberg, K., Dreij, K., Seidel, A., Jernström, B. Chem. Res. Toxicol. (2002) [Pubmed]
  34. Glutathione S-transferases M1/T1 gene polymorphisms and endometriosis: a meta-analysis of genetic association studies. Guo, S.W. Mol. Hum. Reprod. (2005) [Pubmed]
  35. Human glutathione S-transferase M1 null genotype is associated with a high inducibility of cytochrome P450 1A1 gene transcription. Vaury, C., Lainé, R., Noguiez, P., de Coppet, P., Jaulin, C., Praz, F., Pompon, D., Amor-Guéret, M. Cancer Res. (1995) [Pubmed]
  36. p53 mutations in bladder cancer: evidence for exogenous versus endogenous risk factors. Schroeder, J.C., Conway, K., Li, Y., Mistry, K., Bell, D.A., Taylor, J.A. Cancer Res. (2003) [Pubmed]
  37. High-activity microsomal epoxide hydrolase genotypes and the risk of oral, pharynx, and larynx cancers. Jourenkova-Mironova, N., Mitrunen, K., Bouchardy, C., Dayer, P., Benhamou, S., Hirvonen, A. Cancer Res. (2000) [Pubmed]
  38. Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients. Fryer, A.A., Ramsay, H.M., Lovatt, T.J., Jones, P.W., Hawley, C.M., Nicol, D.L., Strange, R.C., Harden, P.N. Carcinogenesis (2005) [Pubmed]
  39. Polymorphic enzymes of xenobiotic metabolism as modulators of acquired P53 mutations in bladder cancer. Brockmöller, J., Kaiser, R., Kerb, R., Cascorbi, I., Jaeger, V., Roots, I. Pharmacogenetics (1996) [Pubmed]
  40. Glutathione S-transferase M1 null genotype is associated with a decreased risk of myocardial infarction. Wilson, M.H., Grant, P.J., Hardie, L.J., Wild, C.P. FASEB J. (2000) [Pubmed]
  41. Glutathione S-transferase polymorphisms and survival in primary malignant glioma. Okcu, M.F., Selvan, M., Wang, L.E., Stout, L., Erana, R., Airewele, G., Adatto, P., Hess, K., Ali-Osman, F., Groves, M., Yung, A.W., Levin, V.A., Wei, Q., Bondy, M. Clin. Cancer Res. (2004) [Pubmed]
  42. Detection of the GSTM1*0 allele by long polymerase chain reaction. Kerb, R., Brockmöller, J., Sachse, C., Roots, I. Pharmacogenetics (1999) [Pubmed]
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