6072 Background: One of the standard therapy in inoperable head and neck squamous cell carcinoma (HNSCC) patients is cetuximab plus radiotherapy. However, the efficacy of this treatment varies greatly among individuals. In an attempt to identify predictive markers to determine the patients most likely to benefit from this treatment, we examined the potential effect on outcome and skin toxicity according to single SNPs in hypoxia-related genes and DNA repair genes. Methods: Sixty-one patients enrolled between May 2006 and August 2011 and diagnosed with HNSCC were included. Data on epithelitis, mucositis and folliculitis were collected in accordance with WHO criteria. SNPs were analyzed in HIF-1α, HIF-2α, HIF-1β, VHL, FIH-1, XRCC1 and XRCC5 in DNA obtained from paraffin-embedded tumor tissues by allelic discrimination in an ABI PRISM 7500 Sequence detection system. Results were correlated with time to progression (TTP), overall survival (OS) and toxicity. Results: The median of TTPand OSwere better in patients with mucositis severe vs mild (17 vs 7 months, p=0.03, and 26 vs 12 months, p=0.016, respectively) and in those with folliculitis severe vs mild (10 versus 7 months, p=0.01, and 26 vs 10 months, p<0.001, respectively). Patients withHIF-1α CT/TT had better OS than those with HIF-1α CC or wild type (28 versus 13 months, p=0.035). Patients with XRCC5 GG/AA genotypes had longer TTP than patients with XRCC5 AG (11 versus 7 months, p=0.035). Conclusions: Our findings indicate that the presence of severe skin toxicities, as well as SNPs in HIF-1α and XRCC5, are associated with interindividual differences in outcome among HNSCC patients.
Polymorphisms in biotransformation and DNA repair genes, and survival on head and neck squamous cell carcinoma