MGMT in glial carcinogenesis. Roles from prevention to treatment

Eur J Cancer Prev. 2022 Nov 1;31(6):568-576. doi: 10.1097/CEJ.0000000000000746. Epub 2022 Jun 3.

Abstract

Many investigations exist regarding the effect of the DNA repair enzyme MGMT (O 6 -methylguanine- DNA-methyltransferase)-encoding gene methylation on the antineoplasticity of temozolomide in glioblastoma patients. However, there exist surprisingly lesser studies regarding the associations between MGMT enzyme biochemistry with glial carcinogenesis. MGMT involves in risk of malignancies associated with ionizing radiation, smoking, exposure to polycyclic aromatic hydrocarbons, chlorinated solvents, vinylchloride and hairdyes. All these factors are also proposed to link with gliomagenesis, yet MGMT interactions with these carcinogens in gliomagenesis are not studied yet. In future, MGMT sequencing may be employed in vulnerable populations working in industries associated with exposure to these carcinogens to develop preventive strategies. Given that MGMT is involved in DNA repair, a polymorphism may simultaneously modify the risk of gliomas while enhancing temozolomide cytotoxicity in both marrow and tumor cells.

MeSH terms

  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / prevention & control
  • Carcinogenesis / genetics
  • Carcinogens
  • DNA
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Dacarbazine
  • Humans
  • O(6)-Methylguanine-DNA Methyltransferase / genetics
  • O(6)-Methylguanine-DNA Methyltransferase / metabolism
  • Polycyclic Aromatic Hydrocarbons*
  • Solvents
  • Temozolomide
  • Tumor Suppressor Proteins / genetics

Substances

  • Carcinogens
  • Polycyclic Aromatic Hydrocarbons
  • Solvents
  • Tumor Suppressor Proteins
  • Dacarbazine
  • DNA
  • DNA Modification Methylases
  • MGMT protein, human
  • O(6)-Methylguanine-DNA Methyltransferase
  • DNA Repair Enzymes
  • Temozolomide