Polymorphisms in DNA mismatch repair pathway genes predict toxicity and response to cisplatin chemoradiation in head and neck squamous cell carcinoma patients.

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 c.-93G>A (rs1800734), c.211+9C>G (rs2303426), c.3133G>A (rs26279), c.1765G>A (rs1047840), and 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 GG and rs9350 CC genotypes compared with patients with GA or AA and CT or TT genotypes, respectively. GG or GA and GT haplotype of rs1047840 and rs9350 SNPs conferred to patients 10.29 and 4.00 more chances of presenting pronounced ototoxicity after treatment than AA genotype and other haplotypes, respectively. Patients with rs1047840 GA or AA genotype and AC haplotype of 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 GG genotype and other haplotypes, respectively. For the first time, our data show preliminary indication that inherited alterations of DNA MMR pathway, related to rs26279, rs1047840 and rs9350 SNPs, modify toxicity and response to chemoradiation in HNSCC, and may contribute to future personalized treatment of patients.