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Genetic polymorphisms in DNA mismatch repair-related genes predict outcome in patients with head and neck squamous cell carcinoma treated with cisplatin and radiotherapy

Date

09 Oct 2016

Session

Poster display

Presenters

Gustavo Lourenço

Citation

Annals of Oncology (2016) 27 (6): 328-350. 10.1093/annonc/mdw376

Authors

G.J. Lourenço1, G.A.S. Nogueira1, L. Lopes-Aguiar1, E.F.D. Costa1, T.R.P. Lima1, M.B. Visacri2, E.C. Pincinato1, L. Calonga3, F.V. Mariano4, A.M.A.M. Altemani4, J.M.C. Altemani5, C.M. Coutinho-Camillo6, M.A.V.F.R. Alves7, P. Moriel2, C.T. Chone3, C.D. Ramos5, C.S.P. Lima7

Author affiliations

  • 1 Laboratory Of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, 13083888 - Campinas/BR
  • 2 Department Of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, 13083970 - Campinas/BR
  • 3 Department Of Ophthalmology And Otorhinolaryngology, Faculty of Medical Sciences, University of Campinas, 13083888 - Campinas/BR
  • 4 Department Of Pathology, Faculty of Medical Sciences, University of Campinas, 13083888 - Campinas/BR
  • 5 Department Of Radiology, Faculty of Medical Sciences, University of Campinas, 13083888 - Campinas/BR
  • 6 Department Of Pathology, A.C. Camargo Cancer Center, São Paulo/BR
  • 7 Department Of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas/BR
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Resources

Background

Cisplatin (CDDP) associated with radiotherapy (RT) has been used in treatment of patients with head and neck squamous cell carcinoma (HNSCC) with distinct results among those with similar clinicopathological aspects. The aim of this study was to access whether MLH1 c. − 93G > A, MSH2 c.211 + 9C > G, MSH3 c.3133G > A, EXO1 c.1765G > A and EXO1 c.2270C > T single nucleotide polymorphisms (SNPs) of the mismatch repair (MMR) pathway, alter the outcome of 90 consecutive HNSCC patients treated with CDDP and RT.

Methods

Genotypes were analyzed by polymerase chain reaction (PCR) based methods in DNA of peripheral blood. Treatment response and toxicities were assessed using conventional criteria.

Results

Patients with the MSH3 c.3133GG genotype and GG or GA genotype were under a 4.27-fold and 10.29-fold increased risks of presenting moderated or severe nephrotoxicity and ototoxicity after chemoradiation than others, respectively. The EXO1 c.1765GA or AA genotype conferred to patients 9.55 more chances of achieving partial (PR) or stable disease (SD) than others. Patients with the EXO1 c.2270CC genotype were under a 4.69-fold and a 4.03-fold increased risks of presenting moderate or severe nephrotoxicity and none or mild ototoxicity after chemoradiation than others. The GT and AC haplotypes of EXO1 c.1765G > A and c.2270C > T SNPs were associated with a 9.11 and 4.00-fold increased risks of none or mild nefrotoxicity and moderate or severe ototoxicity, and a 9.55-fold increased risk of achieving PR or SD than others, respectively.

Conclusions

Our data present, for the first time, preliminary evidence that inherited abnormalities in MMR pathway, related to MSH3 c.3133G > A, EXO1 c.1765G > A and EXO1 c.2270C > T SNPs, may change rate of complete response and side effects in patients with HNSCC treated with CDDP and RT.

Clinical trial identification

Legal entity responsible for the study

University of Campinas

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.

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