An MGMT Allelic Variant Can Affect Biochemical Relapse in Prostate Cancer Patients

Anticancer Res. 2023 Jan;43(1):369-379. doi: 10.21873/anticanres.16172.

Abstract

Background/aim: Prostate cancer (PCa) is one of the most frequent neoplasms in men around the world. In recent years, the search for new biomarkers with greater prognostic potential for PCa has intensified. This study aimed to evaluate single nucleotide polymorphisms (SNPs) and a combined panel of these polymorphisms in relation to biochemical recurrence in patients who were through prostatectomy, with an average of 7 years of follow-up.

Materials and methods: Patients diagnosed with PCa (n=197) participated in this cohort study. Thirteen SNPs were analyzed: rs2279115 (BCL-2), rs26677604 (CASP3), rs1052571 (CASP9), rs11781886 (NKX3-1), rs2735343 (PTEN), rs2494750 (AKT1), rs2699887 (PI3KCA), rs3195676 (AMACR), rs17302090 (AR), rs2536 (mTOR), rs1695 (GSTP1), rs2308321 (MGMT) and rs1544410 (VDR). Variants were combined and four main panels were defined: cell death, cell survival, growth receptors, and metabolism. Genotyping was performed by real-time PCR.

Results: We did not observe any significant relation between the panels of variants analyzed, apart from the rare allele (G) of rs2308321 (MGMT) that was associated with a higher risk of recurrence (p=0.036) when compared to the prevalent (A) in the allelic model.

Conclusion: This MGMT variant occurs in an exon, and it could potentially affect DNA repair and, therefore, the biochemical relapse of PCa patients.

Keywords: MGMT; PSA; SNP; follow-up; prostate cancer; recurrence.

MeSH terms

  • Alleles
  • Cohort Studies
  • DNA Modification Methylases* / genetics
  • DNA Repair Enzymes / genetics
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / pathology
  • Recurrence
  • Tumor Suppressor Proteins / genetics

Substances

  • DNA Modification Methylases
  • DNA Repair Enzymes
  • MGMT protein, human
  • Tumor Suppressor Proteins