m5C修饰核心基因的遗传变异与中国儿童急性淋巴细胞白血病风险相关：一项五中心病例对照研究。
Genetic variants in m5C modification core genes are associated with the risk of Chinese pediatric acute lymphoblastic leukemia: A five-center case-control study.
作者信息
Wang Xueliang, Deng Decheng, Yan Yaping, Cai Mansi, Liu Xiaodan, Luo Ailing, Liu Shanshan, Zhang Xiaohong, Jiang Hua, Liu Xiaoping
机构信息
Department of Hematology/Oncology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Province Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Province Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
出版信息
Front Oncol. 2023 Jan 9;12:1082525. doi: 10.3389/fonc.2022.1082525. eCollection 2022.
OBJECTIVE
To explore the functions of the polymorphisms in 5-methylcytosine (m5C) modification-related coding genes on the susceptibility of pediatric acute lymphoblastic leukemia (ALL).
METHODS
Case-control study and multinomial logistic regression analysis were performed to construct models to evaluate the susceptibility of pediatric ALL. The relationship between five functional SNPs in m5C modification-coding genes and pediatric ALL risk was analyzed. Genotyping of 808 cases and 1,340 healthy samples from South China was identified using a TaqMan assay; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the relationship between the five selected SNPs and pediatric ALL susceptibility.
RESULTS
Among the five analyzed SNPs, rs3764909 and rs10252 variants significantly increased the susceptibility of pediatric ALL, while rs7653521, rs1880948, and rs3740102 variants were not associated with the risk of ALL. Stratification analyses demonstrated that rs3764909 C>A exhibited a significant association with increased pediatric ALL risk in subgroups of common B ALL, pre-B ALL, T-cell ALL, low and middle risk, other gene fusion types, non-gene fusion, hypodiploid, normal diploid, primitive lymphocytes in marrow < 5% on week 12, and minimal residual disease (MRD) <0.01% on week 12 after induced therapy; rs10252 G>A was related to increased risk of ALL children in subgroups of age ≥ 120 months, normal white blood cell (WBC) number, middle risk, non-gene fusion, MRD ≥ 0.01 on days 15-19, and primitive lymphocytes in marrow < 5% on day 33 after induced therapy. Compared with the reference haplotype CAGTA, children who harbored haplotypes CCGTG and ACATA were remarkably related to increased ALL susceptibility. rs3764909 and rs10252 varieties of alleles were not associated with MRD levels after the selected chemotherapeutics.
CONCLUSIONS
In conclusion, rs3764909 and rs10252 variants were enhanced by pediatric ALL risk and were suggested to be potential biomarkers for pediatric ALL.
目的
探讨5-甲基胞嘧啶（m5C）修饰相关编码基因多态性对小儿急性淋巴细胞白血病（ALL）易感性的影响。
方法
采用病例对照研究和多项逻辑回归分析构建模型，评估小儿ALL的易感性。分析m5C修饰编码基因中的5个功能性单核苷酸多态性（SNP）与小儿ALL风险的关系。使用TaqMan检测法对来自中国南方的808例病例和1340例健康样本进行基因分型；计算优势比（OR）和95%置信区间（CI），以评估所选5个SNP与小儿ALL易感性之间的关系。
结果
在分析的5个SNP中，rs3764909和rs10252变异显著增加小儿ALL的易感性，而rs7653521、rs1880948和rs3740102变异与ALL风险无关。分层分析表明，rs3764909 C>A在普通B-ALL、前B-ALL、T细胞ALL、低中危、其他基因融合类型、非基因融合、亚二倍体、正常二倍体、诱导治疗后第12周骨髓原始淋巴细胞<5%以及诱导治疗后第12周微小残留病（MRD）<0.01%的亚组中与小儿ALL风险增加显著相关；rs10252 G>A与年龄≥120个月、白细胞（WBC）数正常、中危、非基因融合、诱导治疗后第15 - 19天MRD≥0.01以及诱导治疗后第33天骨髓原始淋巴细胞<5%的ALL患儿亚组风险增加有关。与参考单倍型CAGTA相比，携带单倍型CCGTG和ACATA的儿童与ALL易感性增加显著相关。所选化疗药物治疗后，rs3764909和rs10252等位基因变异与MRD水平无关。
结论
总之，rs3764909和rs10252变异增加小儿ALL风险，提示其可能是小儿ALL的潜在生物标志物。
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