Polymorphisms in DNA mismatch repair pathway genes predict toxicity and response to cisplatin chemoradiation in head and neck squamous cell carcinoma patients
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Guilherme Augusto Silva Nogueira1, Ericka Francislaine Dias Costa1, Leisa Lopes-Aguiar1, Tathiane Regine Penna Lima1, Marília Berlofa Visacri2, Eder Carvalho Pincinato1, Gustavo Jacob Lourenço3, Luciane Calonga4, Fernanda Viviane Mariano5, Albina Messias de Almeida Milani Altemani5, João Maurício Carrasco Altemani6, Patrícia Moriel2, Carlos Takahiro Chone4, Celso Dario Ramos6 and Carmen Silvia Passos Lima1
1Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
2Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
3Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
4Department of Ophthalmology and Otorhinolaryngology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
5Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
6Department of Radiology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
Carmen Silvia Passos Lima, email: firstname.lastname@example.org
Keywords: head and neck squamous cell carcinoma; mismatch repair pathway; single nucleotide polymorphism; outcome
Received: February 03, 2018 Accepted: March 26, 2018 Published: July 03, 2018
Head and neck squamous cell carcinoma (HNSCC) is treated with cisplatin (CDDP) and radiotherapy (RT), and distinct results are observed among patients with similar clinicopathological aspects. This prospective study aimed to investigate whether MLH1 c.-93G>A (rs1800734), MSH2 c.211+9C>G (rs2303426), MSH3 c.3133G>A (rs26279), EXO1 c.1765G>A (rs1047840), and EXO1 c.2270C>T (rs9350) single nucleotide polymorphisms (SNPs) of the mismatch repair (MMR) pathway change side effects and response rate of 90 HNSCC patients treated with CDDP and RT. DNA from peripheral blood was analyzed by PCR-based methods to obtain genotypes. It was observed 4.27-fold and 4.69-fold increased risks of presenting pronounced nephrotoxicity with treatment in patients with MSH3 GG and EXO1 rs9350 CC genotypes compared with patients with GA or AA and CT or TT genotypes, respectively. MSH3 GG or GA and GT haplotype of EXO1 rs1047840 and rs9350 SNPs conferred to patients 10.29 and 4.00 more chances of presenting pronounced ototoxicity after treatment than MSH3 AA genotype and other EXO1 haplotypes, respectively. Patients with EXO1 rs1047840 GA or AA genotype and AC haplotype of EXO1 rs1047840 and rs9350 SNPs had both 9.55-fold increased risks of achieving partial response or stable disease instead of complete remission after treatment than patients with EXO1 GG genotype and other EXO1 haplotypes, respectively. For the first time, our data show preliminary indication that inherited alterations of DNA MMR pathway, related to MSH3 rs26279, EXO1 rs1047840 and EXO1 rs9350 SNPs, modify toxicity and response to chemoradiation in HNSCC, and may contribute to future personalized treatment of patients.
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