Relationship between clinical toxicities and ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms in cervical cancer patients

Int J Biol Markers. 2018 Jan;33(1):116-123. doi: 10.5301/ijbm.5000279.

Abstract

Background: Several studies have suggested that there are single nucleotide polymorphisms (SNPs) that can be considered potential biomarkers in the prognosis and therapeutic response of cancer patients. The present study investigated the association between ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms and clinical toxicities induced by chemoradiotherapy (CRT) in cervical cancer.

Methods: This hospital-based retrospective cohort study included 260 patients with cervical cancer, FIGO stages Ib2-IVa, who underwent CRT (cisplatin). Genetic polymorphisms analysis was performed by allelic discrimination with real-time polymerase chain reaction (RT-PCR).

Results: Our results indicated a link between ERCC1 rs3212986 and the onset of late gastrointestinal toxicity (p = 0.038). Furthermore, using a recessive model (AA vs. CC/CA), we found that patients carrying AA homozygous genotype presented a fourfold increased risk of developing late gastrointestinal toxicity when compared with patients with the C allele (odds ratio = 3.727, 95% confidence interval, 1.199-11.588; p = 0.017). No association was found regarding the XRCC3 rs861539 polymorphism and any clinical toxicity event.

Conclusions: This is the first study evaluating the relationship between these polymorphisms and clinical toxicities in cervical cancer patients submitted to CRT with cisplatin. These results may contribute toward a better understanding of the influence of genetic polymorphisms in genes associated with DNA repair in the clinical response to CRT of patients with cervical cancer.

Keywords: Cervical cancer; Genetic polymorphisms; Repair genes; Toxicity.

MeSH terms

  • Alleles
  • Biomarkers, Tumor / genetics*
  • Chemoradiotherapy / adverse effects
  • Cisplatin / adverse effects
  • DNA Repair / drug effects
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / etiology*
  • Gastrointestinal Diseases / genetics
  • Gastrointestinal Diseases / pathology
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • X-ray repair cross complementing protein 3
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin