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以及种系多态性与儿童急性淋巴细胞白血病易感性

, , , , and germline polymorphisms and predisposition to childhood acute lymphoblastic leukemia.

作者信息

Al-Zayan Nermeen R, Ashour Mohammed J, Abuwarda Hadeer N, Sharif Fadel A

机构信息

Department of Medical Laboratory Sciences-IUG, Gaza, Palestine.

出版信息

Pediatr Hematol Oncol. 2024;41(2):103-113. doi: 10.1080/08880018.2023.2234946. Epub 2023 Aug 14.

Abstract

Acute lymphoblastic leukemia (ALL) is the most frequent type of pediatric cancer. Germline single nucleotide polymorphisms (SNPs), including (rs10821936 T/C), (rs4132601 T/G), (rs3824662 G/T), (rs2239633 G/A), and (rs3731217 A/C) have been linked to pediatric ALL in different populations. Hitherto, no previous studies have tested the relationship between these SNPs and pediatric ALL in Gaza strip. Therefore, we investigated the association between these polymorphisms and the occurrence of childhood ALL in this part of Palestine. This case-control study recruited 100 healthy controls and 78 ALL patients. Allele-specific PCR (AS-PCR) technique was used for SNPs genotyping. Relevant statistical tests were used and the multifactor dimensionality reduction (MDR) approach was applied in the analysis of gene-gene interactions. Minor alleles of rs10821936 T/C ( = 0.007) and rs4132601 T/G ( = 0.045) were significantly higher in ALL patients. The homozygous (TT) genotype of rs3824662 G/T ( = 0.038), (CC) of rs10821936 T/C ( = 0.008), and (AC and CC) genotypes of rs3731217 A/C ( < 0.0001) were significantly higher in ALL cases. On MDR analysis, the best model for ALL risk was the five-factor model combination of the examined SNPs (CVC = 10/10; TBA = 0.632;  < 0.0001). This work demonstrates the association of rs10821936 T/C, rs4132601 T/G, rs3824662 G/T, and rs3731217 A/C polymorphisms with increased risk of pediatric ALL among a patient cohort from Gaza Strip. Further studies with a larger sample size are needed in order to confirm these findings and test the value of these SNPs in prognosis and treatment sensitivity.

摘要

急性淋巴细胞白血病(ALL)是儿童期最常见的癌症类型。种系单核苷酸多态性(SNP),包括(rs10821936 T/C)、(rs4132601 T/G)、(rs3824662 G/T)、(rs2239633 G/A)和(rs3731217 A/C),已在不同人群中与儿童ALL相关联。迄今为止,此前尚无研究检测这些SNP与加沙地带儿童ALL之间的关系。因此,我们调查了这些多态性与巴勒斯坦这一地区儿童ALL发生之间的关联。这项病例对照研究招募了100名健康对照者和78名ALL患者。采用等位基因特异性PCR(AS-PCR)技术进行SNP基因分型。使用了相关统计检验,并应用多因素降维(MDR)方法分析基因-基因相互作用。rs10821936 T/C(P = 0.007)和rs4132601 T/G(P = 0.045)的次要等位基因在ALL患者中显著更高。rs3824662 G/T的纯合子(TT)基因型(P = 0.038)、rs10821936 T/C的(CC)基因型(P = 0.008)以及rs3731217 A/C的(AC和CC)基因型(P < 0.0001)在ALL病例中显著更高。在MDR分析中,ALL风险的最佳模型是所检测SNP的五因素模型组合(CVC = 10/10;TBA = 0.632;P < 0.0001)。这项研究表明,rs10821936 T/C、rs4132601 T/G、rs3824662 G/T和rs3731217 A/C多态性与加沙地带患者队列中儿童ALL风险增加相关。需要进行更大样本量的进一步研究,以证实这些发现并测试这些SNP在预后和治疗敏感性方面的价值。

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