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儿童白血病和淋巴瘤的病因。

Causes of childhood leukaemia and lymphoma.

作者信息

Lightfoot Tracy J, Roman Eve

机构信息

Leukaemia Research Fund Epidemiology and Genetics Unit, Department of Health Sciences, University of York, YO10 5DD, UK.

出版信息

Toxicol Appl Pharmacol. 2004 Sep 1;199(2):104-17. doi: 10.1016/j.taap.2003.12.032.

Abstract

Childhood cancer is rare comprising less than 1% of all malignancies diagnosed each year in developed countries. Leukaemia is the commonest form of cancer in children accounting for around a third of all childhood cancer, with acute lymphoblastic leukaemia (ALL) being the most prevalent. Biologically specific subtypes of ALL and acute myeloblastic leukaemia (AML), the other major morphological type of childhood leukaemia, are characterised by chromosomal changes. Whilst over 200 genes have been associated with chromosomal translocations, to date, only MLL, TEL, and AML1 have been linked with childhood leukaemia. Interestingly, there is increasing evidence to support the theory that gene rearrangements such as these may originate in utero. As with many other human diseases, both genetic and environmental factors have been implicated in the aetiology of the disease. Although much has been documented with regard to diet, smoking, alcohol consumption and recreational and prescription drug use during pregnancy, there is no consistent evidence to support a link with any of these factors and childhood leukaemia. However, findings from studies investigating prenatal and early life exposures are often based on small numbers of cases as both the type of cancer and exposure are rare. Furthermore, accurate information relating to past exposures can be difficult to obtain and is often reliant on self-reporting. To further our understanding of the aetiology of childhood leukaemia and lymphoma, there are areas which clearly warrant investigation. These include collection of parental dietary folate data combined with genetic analysis of the folate related genes, in utero exposure to DNA topoisomerase II inhibitors, and the possible effects of assisted reproduction technology on disease susceptibility.

摘要

儿童癌症较为罕见,在发达国家每年诊断出的所有恶性肿瘤中占比不到1%。白血病是儿童最常见的癌症形式,约占所有儿童癌症的三分之一,其中急性淋巴细胞白血病(ALL)最为普遍。ALL以及儿童白血病的另一种主要形态学类型急性髓细胞白血病(AML)的生物学特定亚型,其特征在于染色体变化。虽然已有200多个基因与染色体易位有关,但迄今为止,只有MLL、TEL和AML1与儿童白血病相关。有趣的是,越来越多的证据支持这样一种理论,即此类基因重排可能起源于子宫内。与许多其他人类疾病一样,遗传和环境因素都与该疾病的病因有关。尽管关于孕期饮食、吸烟、饮酒以及使用消遣性和处方药的情况已有大量记录,但没有一致的证据支持这些因素中的任何一个与儿童白血病存在关联。然而,调查产前和生命早期暴露情况的研究结果往往基于少量病例,因为癌症类型和暴露情况都很罕见。此外,与过去暴露相关的准确信息可能难以获取,且往往依赖自我报告。为了进一步了解儿童白血病和淋巴瘤的病因,有一些领域显然值得研究。这些领域包括收集父母的膳食叶酸数据并结合对叶酸相关基因的遗传分析、子宫内接触DNA拓扑异构酶II抑制剂的情况,以及辅助生殖技术对疾病易感性的可能影响。

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