中国儿童基因多态性与小儿急性淋巴细胞白血病复发易感性：一项五中心病例对照研究
gene polymorphism and pediatric acute lymphoblastic leukemia relapse susceptibility among Chinese children: a five-center case-control study.
作者信息
Ding Wenjiao, Wang Dao, Cai Mansi, Yan Yaping, Liu Shanshan, Liu Xiaodan, Luo Ailing, Deng Decheng, Liu Xiaoping, Jiang Hua
机构信息
Department of Hematology and Oncology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Province Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
出版信息
Front Oncol. 2023 Nov 2;13:1203002. doi: 10.3389/fonc.2023.1203002. eCollection 2023.
OBJECTIVE
polymorphisms' role in pediatric acute lymphoblastic leukemia (ALL) relapse susceptibility remains undiscovered.
METHODS
A case-control designed and multiple logistic regression model was performed to evaluate the overall risk of pediatric ALL and five single-nucleotide polymorphisms (SNPs) of gene (rs35997018 C>T, rs1106042 A>G, rs7957349 C>G, rs10773771 C>T, and rs10848087 A>G) in 785 cases and 1,323 controls, which were genotyped by TaqMan assay. The odds ratio (OR) and its 95% confidence interval (CI) were used to estimate the relationship. Stratified analysis was used to investigate the correlation of rs1106042 and rs10773771 genotypes and pediatric ALL relapse susceptibility in terms of age, sex, number of white blood cells (WBC), immunophenotyping, gene fusion type, karyotype, primitive/naïve lymphocytes, and minimal residual disease (MRD) in bone marrow. Finally, the haplotype analysis was performed to appraise the relationship between inferred haplotypes of and pediatric ALL risk.
RESULTS
Among the five analyzed SNPs, rs1106042 A>G was related to increased ALL risk, and rs10773771 C>T was related to decreased ALL risk. Compared to the GG genotype, the rs1106042 GA/AA had a deleterious effect on children of age <120 months, who were female and male, had high or average number of WBC, pro-B ALL, pre-B ALL, T-ALL, low- and middle-risk ALL, E2A-PBX fusion gene, non-gene fusion, abnormal diploid, high hyperdiploid, hypodiploid, and normal diploid. Moreover, rs1106042 A>G harmfully affected primitive/naïve lymphocytes and MRD on days 15-19, day 33, and week 12. On the contrary, rs10773771 TC/CC exhibited a protective effect on ALL children with the TEL-AML fusion gene. Haplotype analysis demonstrated that haplotypes CAGT, TACC, TACT, and TAGT were significantly associated with increased pediatric ALL relapse susceptibility.
CONCLUSION
rs1106042 A>G was related to increased ALL risk, and rs10773771 C>T was linked to decreased ALL risk in eastern Chinese children. Rs1106042 GA/AA may predict poor prognosis.
目的
多态性在小儿急性淋巴细胞白血病（ALL）复发易感性中的作用仍未明确。
方法
采用病例对照设计和多因素logistic回归模型，对785例病例和1323例对照进行小儿ALL总体风险及某基因的5个单核苷酸多态性（SNP，rs35997018 C>T、rs1106042 A>G、rs7957349 C>G、rs10773771 C>T和rs10848087 A>G）评估，通过TaqMan检测法进行基因分型。用比值比（OR）及其95%置信区间（CI）评估两者关系。采用分层分析研究rs1106042和rs10773771基因型与小儿ALL复发易感性在年龄、性别、白细胞（WBC）计数、免疫表型、基因融合类型、核型、原始/幼稚淋巴细胞及骨髓微小残留病（MRD）方面的相关性。最后进行单倍型分析，评估该基因推断单倍型与小儿ALL风险的关系。
结果
在分析的5个SNP中，rs1106042 A>G与ALL风险增加相关，rs10773771 C>T与ALL风险降低相关。与GG基因型相比，rs1106042 GA/AA基因型对年龄<120个月的儿童有有害影响，无论男女，WBC计数高或中等，前B-ALL、前体B-ALL、T-ALL、低中危ALL、E2A-PBX融合基因、非基因融合、异常二倍体、高超二倍体、亚二倍体及正常二倍体患儿。此外，rs1106042 A>G对第15 - 19天、第33天和第12周时的原始/幼稚淋巴细胞及MRD有不良影响。相反，rs10773771 TC/CC基因型对携带TEL-AML融合基因的ALL患儿有保护作用。单倍型分析表明，单倍型CAGT、TACC、TACT和TAGT与小儿ALL复发易感性增加显著相关。
结论
在中国东部儿童中，rs1106042 A>G与ALL风险增加相关，rs10773771 C>T与ALL风险降低相关。rs1106042 GA/AA可能预示预后不良。
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