Understanding Role of DNA Repair and Cytochrome p-450 Gene Polymorphisms in Cervical Cancer Patient Treated With Concomitant Chemoradiation

Br J Biomed Sci. 2022 Feb 24:79:10120. doi: 10.3389/bjbs.2021.10120. eCollection 2022.

Abstract

Background: Evidences suggest that single nucleotide polymorphisms (SNPs) can be considered as potential biomarkers for disease progression and therapeutic response in cervical cancer. The present study investigated the association of CYP1A1 T>C (rs4646903), CYP1A1 A>G (rs1048943), CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), XRCC1 G>A (rs25487), XRCC2 G>A (rs3218536) and XRCC3 C>T (rs861539) polymorphisms with treatment outcome of cisplatin based chemoradiation (CRT). Methods: Total 227 cervical cancer cases, treated with the same chemoradiotherapy regimen were selected for the study. Genotyping analysis was performed by PCR-restriction fragment length polymorphisms (PCR-RFLP). Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Association of all clinical data (responses, recurrence and survival of patients) and single nucleotide polymorphisms (SNPs) was analysed by using SPSS (version 21.0). Results: Patients with TA/AA genotype of CYP2E1 T>A polymorphism showed significantly poor response while those with GC/CC genotype of RAD51 G>C showed better response (p = 0.008, p = 0.014 respectively). Death was significantly higher in patients with GG genotypes of RAD51 G>C and XRCC1 G>A (p = 0.006, p = 0.002 respectively). Women with GC+CC genotype of RAD51 G>C and AG+GG of XRCC1 showed better survival and also reduced risk of death (HR = 0.489, p = 0.008; HR = 0.484, p = 0.003 respectively). Conclusion: Results suggested that CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), and XRCC1 G>A (rs25487) polymorphisms may be used as predictive markers for clinical outcomes in cervical cancer patients undergoing cisplatin based concomitant chemoradiotherapy.

Keywords: CYP1A1; CYP2E1; DNA repair gene; cervical cancer; polymorphisms; treatment outcome.

MeSH terms

  • Case-Control Studies
  • Chemoradiotherapy
  • Cisplatin / therapeutic use
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 Enzyme System* / genetics
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide
  • Uterine Cervical Neoplasms* / drug therapy
  • Uterine Cervical Neoplasms* / radiotherapy
  • X-ray Repair Cross Complementing Protein 1 / genetics

Substances

  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • XRCC2 protein, human
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 CYP1A1
  • Cisplatin