Genetic polymorphisms of genes involved in oxidative stress and inflammatory management in oncopediatric patients with chemo-induced oral mucositis

Abstract

Objective: Oral mucositis (OM) is a painful inflammatory oral condition that affects children who undergo chemotherapy. Oxidative stress is a known OM mediator and pro-inflammatory cytokines contribute to the amplification of the immune response. To investigate the possible associations of rs4880 (superoxide dismutase 2, SOD2 47 C/T), rs7943316 (catalase, CAT -21 A/T), rs1800629 (tumor necrosis factor α, TNF- α -308 G/A), and rs1800795 (interleukin 6, IL-6 -174 G/C) polymorphisms with chemo-induced OM occurrence and severity in oncopediatric patients.

Methodology: We conducted a single-center, observational cross-sectional study with sample collection of oral epithelial cells from 95 children and adolescents with hematological cancers who underwent chemotherapy, followed by genomic DNA extraction. Single-nucleotide polymorphisms (SNPs) were assessed with PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). Demographic data and information concerning OM occurrence were obtained from dental charts of the multidisciplinary oral care team. Information on OM severity was obtained from appropriately-filled Oral Assessment Guide records. Descriptive and inferential statistics were conducted with Student's T test, chi-squared test, and Fisher's exact test, with p≤0.05.

Results: The mean age was 10 years-old and most patients were male individuals (57.89%). Female sex was considered a protective factor for OM occurrence (OR=4.83; CI=[1.14; 16.57]). The AA genotype for CAT was the most frequent amongst individuals with severe OM (p=0.04). The GA genotype for TNF- α was the most frequent amongst individuals without severe OM (p=0.03). For SOD2 and IL-6 , the most frequent genotypes were CT and GG respectively for all groups (p>0.05).

Conclusion: The AA genotype for CAT -21 A/T was a tendency among the group with severe OM. Data on TNF- α -308 G/A were inconclusive. No associations were detected for SOD2 47 C/T and IL-6 -174 G/C polymorphisms in oncopediatric patients with chemo-induced oral mucositis.

Figure 1. Representative fragments of PCR-RFLP reactions for each of the studied SNPs. A) Amplified fragments for each SNP: L – DNA ladder; SOD 2 (246 bp); CAT (249 bp); TNF- α (107 bp); IL-6 (156 bp). B) SOD 2 restriction fragments: CT (246, 157, 89 bp) and TT (157, 89 bp); C) CAT restriction fragments: TT (249 bp), AA (175, 74 bp) and AT (249, 175, 74 bp). D) TNF- α restriction fragments: GA (107, 87 bp), GG (107bp) and AA (87 bp). E) IL-6 restriction fragments: CC (117bp), GG (139bp), GC (139, 117bp)