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

Abstract

Genetic polymorphisms of genes involved in oxidative stress and inflammatory management in oncopediatric patients with chemoinduced oral mucositis 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. Objective: 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 chemoinduced 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.

DNA Methyltransferase Genes Are Associated with Oral Mucositis and Creatinine Levels in Oncopediatric Patients

“…Genetic polymorphisms in the context of chemo-induced OM in children have already been addressed in genes involved in inflammatory mechanisms, oxidative stress, epigenetics, and MTX ® and vitamin D metabolism [ 11 , 17 , 18 ]. Regarding the methylation profile, only the global and site-specific methylation profiles in the gene involved in vitamin D metabolism have been evaluated [ 18 , 19 ].…”

CAT -21A>T Variant Alters Hydroxyurea Pharmacokinetic Parameters in Brazilian Children with Sickle Cell Anemia

“…These results suggest that the variant CAT -21T allele in homozygous trends to increase HU clearance decreasing Cmax. Reports regarding the effect of variant -21A>T in CAT expression are controversial [10][11][12][13]. Of these studies, only Saify et al [13] investigated the association between this variant and CAT expression.…”

“…Reports regarding the effect of variant -21A>T in CAT expression are controversial [10][11][12][13]. Of these studies, only Saify et al [13] investigated the association between this variant and CAT expression. Taking into account its association with an increase in CAT mRNA and the fact that HU can act as a catalase-activated pro-drug [8], our findings suggest that carriers of the variant -21TT genotype produce higher prodrug levels.…”

“…This enzyme, encoded by the CAT gene, located on chromosome 11 (11p13.31), is most expressed in the liver, kidney, and erythrocytes [9,10]. Although controversial, the polymorphism -21A>T (rs7943316) in the promoter region of the CAT gene has been linked to changes in CAT transcription and enzymatic activity [10][11][12][13]. The present study investigated the effects of the CAT -21A>T variant on pharmacokinetic (PK) parameters in SCA children undergoing HU therapy.…”

Polymorphism but not methylation status in the vitamin D receptor gene contributes to oral mucositis in children

“…Studies addressing genetic markers such as single nucleotide polymorphisms (SNPs) in the context of oral mucositis in oncopaediatric patients have already been conducted in China (Lu et al, 2021), the Netherlands (Den Hoed et al, 2015; Gutierrez‐Camino et al, 2017; Oosterom, Berrevoets, et al, 2018), Mexico (Ruiz‐Argüelles et al, 2007) and Turkey (Bektaş‐Kayhan et al, 2012), among others. We are the only group to date to conduct studies of this nature in Brazil (Coêlho et al, 2022; Viana Filho et al, 2021). The genes investigated in these studies comprise genes involved in inflammation, oxidative stress, membrane proteins related to drug resistance, MTX® metabolism and micro‐RNAs.…”