ABCG2 polymorphism, age and leukocyte count may contribute to oral mucositis in oncopediatric patients

Abstract

The study investigated the relationship between genetic polymorphisms and the development of oral mucositis in pediatric patients undergoing chemotherapy involving methotrexate. A longitudinal study was conducted with 64 patients, and oral mucositis was evaluated by the modified Oral Assessment Guide, which aims to diagnose and classify oral mucositis. Epithelial cells were obtained by mouthwash and DNA was extracted. The polymorphisms MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) and ABCG2 (rs2231142) were analyzed by PCR-RFLP method. Demographic, hematological and biochemical data were collected from medical records. Statistical analysis was performed using the SPSS software adopting a p-value of 0.05. Male sex predominated (56.2%), and the mean age was 10.8 years (± 4.9). Oral mucositis affected 65.6% of the patients, of which 61.9% developed the severe form of the disease. For the ABCG2 gene (rs2231142), the rare A allele and CA genotype were more frequent in individuals with mucositis (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). The severity of the disease was mainly observed in younger patients (median = 9 years; p=0.02). Patients with severe oral mucositis presented lower leukocytes count (median = 2.150 mm3) compared to patients with the mild/moderate form (median = 4.200 mm3; p=0.03). Female patients and each 10,000-platelet increase were protective factors against the onset of oral mucositis (p=0.02). It is concluded that rs2231142 polymorphism increases the likelihood of oral mucositis and younger patients and patients with low leukocytes counts are more likely to develop severe form.

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

“…In the context of chemo-induced oral mucositis (OM), one SNP from this family was studied ( DNMT3B rs2424913) but no association was detected [ 11 ]. Chemo-induced OM is the most frequent inflammatory condition resulting from chemotherapy treatment for hematologic malignancies in children and adolescents [ 12 , 13 ].…”

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

“…In the present study, it was observed that the group that developed mucositis was also the group that had the lowest leukocyte and platelet counts (Table 1). Previous studies have discussed this relationship (Curra et al, 2021), including some conducted by the same research group as this study (Damascena et al, 2020;Viana-Filho et al, 2021). Thus, it has already been suggested that a low leukocyte and platelet count may favour the exacerbation of the inflammatory response of individuals to chemotherapy, as they will be insufficient to be able to mediate tissue recovery (Repsold & Joubert, 2021).…”

“…It is known that oral mucositis is a multifactorial disease, and data such as age, sex, nutrition, genetics, biochemistry and others are associated with the development of this inflammation (Damascena et al, 2020). Our group has been dedicated to the study of genetic polymorphisms in this context, and the present study adds information to the list of genes that we have already associated with chemo‐induced oral mucositis in paediatric patients with haematological neoplasms: ABCG2 (rs2231142) (Viana‐Filho et al, 2021), CAT (rs7943316) (Coêlho et al, 2022), and now VDR (rs1544410 and rs2228570). In addition to these genes, the literature has already shown association with ABCC4 (rs7317112), MDR‐1 (rs1045642 ), MTHFR (rs1801133) and miR‐1206 (rs2114358) (Bektaş‐Kayhan et al, 2012; Den Hoed et al, 2015, Gutierrez‐Camino et al, 2017; Lu et al, 2021).…”

“…The limitations of our study have already been explored previously (Coêlho et al, 2022;Viana-Filho et al, 2021) and can be listed: a study power <80% due to the small sample size, as this was a single-centre study based on an adverse event (oral mucositis) of a rare disease (haematological neoplasms); the gap between sample collections due to the COVID-19 pandemic, which also contributed to the small sample size; dependence on medical records duly completed by the hospital staff so that patients could be included in the research. Even considering these limitations, our data are unpublished and can be used as a guide for intervention strategies as well as studies with other populations and with a larger sample size.…”

“…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.…”