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

Author:

Soares Sílvia1,Nogueira Augusto12,Coelho Ana1,Assis Joana13,Pereira Deolinda14,Bravo Isabel5,Medeiros Rui126

Affiliation:

1. Molecular Oncology and Viral Pathology Group – Research Center, Portuguese Institute of Oncology, Porto - Portugal

2. Research Department, Portuguese League Against Cancer (NRNorte), Porto - Portugal

3. FMUP, Faculty of Medicine of Porto University, Porto - Portugal

4. Oncology Department, Portuguese Institute of Oncology, Porto - Portugal

5. Medical Physics, Radiobiology and Radioprotection Group – Research Center, Portuguese Institute of Oncology, Porto - Portugal

6. CEBIMED, Faculty of Health Sciences of Fernando Pessoa University, Porto - Portugal

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.

Publisher

SAGE Publications

Subject

Cancer Research,Clinical Biochemistry,Oncology,Pathology and Forensic Medicine

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