{"title":"儿童急性淋巴细胞白血病的非同源末端连接基因型、mRNA 表达和 DNA 修复能力","authors":"Chao-Chun Chen, Wen-Shin Chang, Jen-Sheng Pei, Chien-Chung Kuo, Chung-Hsing Wang, Yun-Chi Wang, Pei-Chen Hsu, Jie-Long He, Jian Gu, DA-Tian Bau, Chia-Wen Tsai","doi":"10.21873/cgp.20436","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL.</p><p><strong>Materials and methods: </strong>Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation was investigated by examining mRNA transcript expression and the capacity for overall and precise NHEJ repair.</p><p><strong>Results: </strong>The variant genotypes of XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 were significantly associated with increased odds of childhood ALL. Further analysis based on susceptibility genotypes showed no significant differences in mRNA transcript expression levels among childhood ALL cases with various putative high-risk genotypes, except XRCC6 rs5751129. Moreover, the overall NHEJ repair capacity was similar among carriers of different XRCC4, XRCC5, and XRCC6 genotypes. However, it is worth noting that individuals carrying the variant C allele at XRCC6 rs5751129 exhibited lower precise NHEJ repair capacity compared to those with the wild-type T allele.</p><p><strong>Conclusion: </strong>Our study identified significant associations between XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 genotypes and childhood ALL. Notably, lower transcriptional expression and reduced precise NHEJ repair capacity were observed in patients carrying the C allele of XRCC6 rs5751129. Further investigations are required to gain deeper insights into childhood ALL development.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 2","pages":"144-157"},"PeriodicalIF":2.6000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10905275/pdf/","citationCount":"0","resultStr":"{\"title\":\"Non-homologous End-joining Genotype, mRNA Expression, and DNA Repair Capacity in Childhood Acute Lymphocytic Leukemia.\",\"authors\":\"Chao-Chun Chen, Wen-Shin Chang, Jen-Sheng Pei, Chien-Chung Kuo, Chung-Hsing Wang, Yun-Chi Wang, Pei-Chen Hsu, Jie-Long He, Jian Gu, DA-Tian Bau, Chia-Wen Tsai\",\"doi\":\"10.21873/cgp.20436\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aim: </strong>The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL.</p><p><strong>Materials and methods: </strong>Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation was investigated by examining mRNA transcript expression and the capacity for overall and precise NHEJ repair.</p><p><strong>Results: </strong>The variant genotypes of XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 were significantly associated with increased odds of childhood ALL. Further analysis based on susceptibility genotypes showed no significant differences in mRNA transcript expression levels among childhood ALL cases with various putative high-risk genotypes, except XRCC6 rs5751129. Moreover, the overall NHEJ repair capacity was similar among carriers of different XRCC4, XRCC5, and XRCC6 genotypes. However, it is worth noting that individuals carrying the variant C allele at XRCC6 rs5751129 exhibited lower precise NHEJ repair capacity compared to those with the wild-type T allele.</p><p><strong>Conclusion: </strong>Our study identified significant associations between XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 genotypes and childhood ALL. Notably, lower transcriptional expression and reduced precise NHEJ repair capacity were observed in patients carrying the C allele of XRCC6 rs5751129. Further investigations are required to gain deeper insights into childhood ALL development.</p>\",\"PeriodicalId\":9516,\"journal\":{\"name\":\"Cancer Genomics & Proteomics\",\"volume\":\"21 2\",\"pages\":\"144-157\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10905275/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Genomics & Proteomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21873/cgp.20436\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Genomics & Proteomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/cgp.20436","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
背景/目的：非同源末端连接（NHEJ）修复能力在维持基因组稳定性和致癌过程中发挥着关键作用。然而，有关 NHEJ 相关基因参与儿童急性淋巴细胞白血病（ALL）的文献很少。我们的研究旨在阐明 X 射线修复交叉互补组 4（XRCC4）（rs6869366、rs2075685、rs2075686、rs28360071、rs3734091、rs28360317、rs1805377）、XRCC5（rs828907、rs11685387、rs9288518）、XRCC6（rs5751129、rs2267437、rs132770、rs132774）、XRCC7 rs7003908 和 DNA 连接酶 IV (LIG4) rs1805388 对儿童 ALL 患病几率的影响。材料与方法：测定了266例病例和266例对照的NHEJ相关基因的基因型，并通过检测mRNA转录本的表达以及整体和精确的NHEJ修复能力来研究基因型与表型的相关性：结果：XRCC4 rs3734091、rs28360071、XRCC5 rs828907和XRCC6 rs5751129的变异基因型与儿童ALL发病几率增加显著相关。基于易感基因型的进一步分析表明，除 XRCC6 rs5751129 外，具有各种推测高危基因型的儿童 ALL 病例的 mRNA 转录物表达水平无明显差异。此外，不同XRCC4、XRCC5和XRCC6基因型携带者的总体NHEJ修复能力相似。然而，值得注意的是，与野生型T等位基因携带者相比，XRCC6 rs5751129的变异C等位基因携带者表现出较低的精确NHEJ修复能力：我们的研究发现了 XRCC4 rs3734091、rs28360071、XRCC5 rs828907 和 XRCC6 rs5751129 基因型与儿童 ALL 之间的重要关联。值得注意的是，在携带 XRCC6 rs5751129 的 C 等位基因的患者中观察到较低的转录表达和较低的精确 NHEJ 修复能力。要更深入地了解儿童 ALL 的发展，还需要进一步的研究。
Non-homologous End-joining Genotype, mRNA Expression, and DNA Repair Capacity in Childhood Acute Lymphocytic Leukemia.
Background/aim: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL.
Materials and methods: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation was investigated by examining mRNA transcript expression and the capacity for overall and precise NHEJ repair.
Results: The variant genotypes of XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 were significantly associated with increased odds of childhood ALL. Further analysis based on susceptibility genotypes showed no significant differences in mRNA transcript expression levels among childhood ALL cases with various putative high-risk genotypes, except XRCC6 rs5751129. Moreover, the overall NHEJ repair capacity was similar among carriers of different XRCC4, XRCC5, and XRCC6 genotypes. However, it is worth noting that individuals carrying the variant C allele at XRCC6 rs5751129 exhibited lower precise NHEJ repair capacity compared to those with the wild-type T allele.
Conclusion: Our study identified significant associations between XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 genotypes and childhood ALL. Notably, lower transcriptional expression and reduced precise NHEJ repair capacity were observed in patients carrying the C allele of XRCC6 rs5751129. Further investigations are required to gain deeper insights into childhood ALL development.
期刊介绍：
Cancer Genomics & Proteomics (CGP) is an international peer-reviewed journal designed to publish rapidly high quality articles and reviews on the application of genomic and proteomic technology to basic, experimental and clinical cancer research. In this site you may find information concerning the editorial board, editorial policy, issue contents, subscriptions, submission of manuscripts and advertising. The first issue of CGP circulated in January 2004.
Cancer Genomics & Proteomics is a journal of the International Institute of Anticancer Research. From January 2013 CGP is converted to an online-only open access journal.
Cancer Genomics & Proteomics supports (a) the aims and the research projects of the INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH and (b) the organization of the INTERNATIONAL CONFERENCES OF ANTICANCER RESEARCH.
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