Genetic Polymorphisms in Genes Involved in Oxidative Stress and Their Association with Radiotherapy Toxicity among Head and Neck Cancer Patients

BACKGROUND: The present study was planned to examine the possible association of polymorphisms in the superoxide dismutase and catalase genes with adverse normal tissue effects or injury resulting from radiotherapy in HNC patients. METHODS: A total of two hundred and fifty head and neck cancer (HNC) patients undergoing therapeutic radiotherapy were enrolled in this study, wherein acute radiation induced toxicity and treatment response were systematically documented. The investigation aimed to assess the potential association between oxidative stress-related gene polymorphisms and susceptibility to acute skin toxicity. Specifically, single nucleotide polymorphisms (SNPs) in SOD1 (A251G, rs2070424), SOD2 (C299T, rs1141718), SOD3 (G172A, rs2536512), and two SNPs in the CAT gene (A21T, rs7943316; C262T, rs1001179) were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The findings revealed a statistically significant negative association between both the combined variant genotype and the heterozygous SOD3 G172A genotype and the risk of acute radiation-induced skin toxicity, suggesting a potential protective effect (OR = 0.48, 95% CI: 0.26-0.88; p = 0.018). In contrast, the homozygous recessive SOD3 172A/A genotype demonstrated a strong positive correlation with the incidence of oral mucositis in HNC patients, exhibiting a markedly elevated risk (OR = 10.47, 95% CI: 4.48-24.44; p < 0.0001). Additionally, individuals carrying the heterozygous 172G/A genotype showed a 2.25-fold increased susceptibility to severe mucositis (OR = 2.25, 95% CI: 1.21-4.17; p = 0.009). Furthermore, the heterozygous A21T genotype of the CAT gene (rs7943316) was significantly associated with an increased risk of oral mucositis following radiotherapy in HNC patients (OR = 1.79, 95% CI: 1.00-3.22; p = 0.049). CONCLUSION: The analysis of genetic polymorphisms in extracellular superoxide dismutase (SOD3) revealed a statistically significant association with radiation-induced skin toxicity and mucositis among HNC patients in the studied population.