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.

摘要 本研究探讨了接受甲氨蝶呤（methotrexate）化疗的儿科患者的遗传多态性与口腔黏膜炎（oral mucositis）发生发展的关联。本研究纳入64例患者开展纵向研究，采用改良版口腔评估指南（modified Oral Assessment Guide）对口腔黏膜炎进行诊断与分级。通过漱口液采集上皮细胞并提取基因组DNA，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法分析MTHFR基因rs1801133位点、DNMT3B基因rs2424913位点、ABCC2基因rs717620位点、ABCG2基因rs2231137位点及ABCG2基因rs2231142位点的多态性。从患者病历中收集人口统计学、血液学及生化指标数据，采用SPSS软件进行统计学分析，检验水准设定为P=0.05。研究对象中男性占比56.2%，平均年龄为10.8岁（±4.9岁）。65.6%的患者发生口腔黏膜炎，其中61.9%发展为重度口腔黏膜炎。针对ABCG2基因rs2231142位点，罕见A等位基因与CA基因型在口腔黏膜炎患者中更为常见（P=0.02；相对危险度（RR）=0.60；95%置信区间（CI）=0.387~0.813）。重度口腔黏膜炎主要见于年龄较小的患者（中位数=9岁；P=0.02）。与轻/中度口腔黏膜炎患者（白细胞计数中位数为4.200 mm³）相比，重度口腔黏膜炎患者的白细胞计数更低（中位数为2.150 mm³；P=0.03）。女性患者及血小板计数每升高10000单位均为口腔黏膜炎发生的保护因素（P=0.02）。本研究结论认为，rs2231142多态性会增加口腔黏膜炎的发病风险，年轻患者与白细胞计数较低的患者更易发展为重度口腔黏膜炎。