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Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma

  • Original Article – Cancer Research
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Abstract

Purpose

We examined the influence of OGG1 c.977C>G (rs1052133), APEX1 c.444T>G (rs1130409), XRCC1 c.-77T>C (rs3213245), c.580C>T (rs1799782), c.839G>A (rs25489) and c.1196G>A (rs25487) single-nucleotide polymorphisms (SNPs), involved in base-excision repair (BER) pathway, on oropharyngeal squamous cell carcinoma (OPSCC) risk and prognosis.

Methods

Aiming to identify the genotypes, DNA from 200 consecutive OPSCC patients and 200 controls was analyzed by PCR-RFLP. The prognostic impact of genotypes of SNPs on progression-free survival (PFS) and overall survival of OPSCC patients was examined using the Kaplan–Meier estimates and Cox regression analyses.

Results

XRCC1 c.580CT or TT genotypes (19.5 vs. 11.0 %, P = 0.04) and XRCC1 TTGG haplotype from c.-77T>C, c.580C>T, c.839G>A and c.1196G>A SNPs (17.5 vs. 10.0 %, P = 0.04) were more common in patients with OPSCC than in controls. Carriers of combined genotypes of c.580C>T and TTGG haplotype of XRCC1 gene were under 3.35- and 3.22-fold increased risk of OPSCC than others. For survival analysis, we selected only patients with tumor at stage IV. The median follow-up time was 24.5 months. At 24 months of follow-up, PFS was shorter in patients with OGG1 c.977CC genotype when compared with others genotypes (35.5 vs. 52.1 %, log-rank test, P = 0.03). After multivariate Cox analysis, patients with OGG1 c.977CC genotype had more chance to present tumor progression when compared with others (HR 1.68, P = 0.02).

Conclusions

Our data present, for the first time, evidence that inherited OGG1 c.977C>G; XRCC1 c.-77T>C, c.580C>T, c.839G>A and c.1196G>A abnormalities of DNA BER pathway are important determinants of OPSCC and predictors of patient outcomes.

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Financial support

São Paulo Research Foundation (FAPESP) (Grant #2012/18623-1) funded this study.

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Authors and Affiliations

  1. Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária “Zeferino Vaz”, Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil

    Ericka Francislaine Dias Costa, Erika Stocco Santos, Vitor Teixeira Liutti, Frederico Leal, Vivian Castro Antunes Santos, José Augusto Rinck-Junior, Carmen Silvia Passos Lima & Gustavo Jacob Lourenço

  2. Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil

    Fernanda Viviane Mariano & Albina Altemani

  3. Department of Pathology, A. C. Camargo Cancer Center, São Paulo, São Paulo, Brazil

    Cláudia Malheiros Coutinho-Camillo

Authors
  1. Ericka Francislaine Dias Costa
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  2. Erika Stocco Santos
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  3. Vitor Teixeira Liutti
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  4. Frederico Leal
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  11. Gustavo Jacob Lourenço
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Correspondence to Gustavo Jacob Lourenço.

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The authors declare that they have no conflicts of interest.

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The study was approved according to the institutional review board guidelines (Number 446/2005) and according to the Declaration of Helsinki, where all subjects provided written informed consent.

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Costa, E.F.D., Santos, E.S., Liutti, V.T. et al. Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma. J Cancer Res Clin Oncol 142, 1917–1926 (2016). https://doi.org/10.1007/s00432-016-2202-8

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