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.
Genotypes were analyzed by polymerase chain reaction (PCR) based methods in DNA of peripheral blood. Treatment response and toxicities were assessed using conventional criteria.
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.
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
All authors have declared no conflicts of interest.