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

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Dias Costa, Ericka Francislaine ; Santos, Erika Stocco ; Liutti, Vitor Teixeira ; Leal, Frederico ; Antunes Santos, Vivian Castro ; Rinck-Junior, Jose Augusto ; Viviane Mariano, Fernanda ; Malheiros Coutinho-Camillo, Claudia ; Altemani, Albina ; Passos Lima, Carmen Silvia ; Lourenco, Gustavo Jacob

• Document type: Journal article
• Source: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY; v. 142, n. 9, p. 1917-1926, SEP 2016.
• Web of Science Citations: 4

Abstract

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. 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. 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). 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. (AU)

• FAPESP's process: 12/18623-1 - Influence of polymorphisms in genes related to DNA repair system in the susceptibility to squamous cell carcinoma of the oropharynx
• Grantee: Erika Stocco dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation