Childhood Cancer Pooling Project

儿童ALL是儿童中最主要的癌症形式，但其原因和危险因素在很大程度上仍然未知。一些因素，如唐氏综合症，其他特殊的遗传异常，同卵双胞胎中有一个患有白血病，以及电离辐射暴露（在子宫和产后），一直与儿童ALL和急性髓性白血病（AML）有关；然而，这些条件只能解释一小部分病例（Robison L, 1995）。事实上，超过90%的儿童白血病病例缺乏合理的病因学解释（Pui C-H, 1995）。2002年3月，在国家癌症研究所召开了一次研讨会，以确定紧急研究需求并促进跨学科合作方法（Linet M, 2003）。在NCI关于儿童癌症病因中基因-环境相互作用的研讨会上，出生体重和儿童白血病的综合分析的想法诞生了。在题为“生命周期范式在儿童癌症流行病学中的应用”的演讲中，我讨论了高出生体重与儿童ALL的关系。根据Ross（1996）的综述，在16项研究中，有12项研究表明，与正常出生体重相比，高体重儿童（bb0 4000 g）患白血病的风险总体上增加了2倍，我回顾了1996年以来的研究。我的演讲将这种关联扩展到除了最近的一项研究之外的所有研究（Westergaard T, 1997; Ross J,1997; Roman E,1997; Reynolds P, 2002），确定了AML的潜在类似关联以及出生体重对5岁以下被诊断患有癌症的儿童的潜在更大影响。我的演讲以描述出生体重的主要决定因素结束（Hennessey E, 1998），并根据Westergaard（1997）和Broomhall（1983）的研究，检查了儿童早期生长在ALL病因学途径中的潜在作用，这与乳腺癌的研究相似（De Stavola B, 2000）。我呼吁研究人员检查出生体重的主要决定因素对儿童白血病风险的影响。在会议期间，Joachim Schuz博士和其他人表示，他们有兴趣开展合作，通过诊断亚型和其他因素来研究出生体重在儿童白血病中的作用，因为儿童ALL和AML是罕见疾病，在单一研究中患者太少，无法进行感兴趣的分析。在那一年里，我和舒兹博士充实了对这一领域进行综合分析的想法，并向潜在的合作者发出了一封邀请函。目的：出生体重与儿童期ALL和AML合并分析的目的是：1。1 .根据诊断年龄和诊断亚型，检查出生体重与儿童白血病的关系；如果出现出生体重相关，检查与出生体重相关的主要因素的影响，以及婴儿喂养或幼儿期生长是否会改变这种关系。

Childhood ALL is the most predominant form of cancer in children, but its causes and risk factors remain largely unknown. A few factors, such as Down's Syndrome, other specific genetic abnormalities, being an identical twin of a sibling with leukemia, and ionizing radiation exposure (both in utero and postnatal), have been consistently linked to childhood ALL and acute myeloid leukemia (AML); however these conditions only explain a small fraction of cases (Robison L, 1995). Indeed a plausible etiologic explanation is lacking for more than 90% of cases of childhood leukemia (Pui C-H, 1995). In the March 2002, a workshop was convened at the National Cancer Institute to identify urgent research needs and facilitate collaborative interdisciplinary approaches (Linet M , 2003). During the NCI Workshop on Gene-Environment Interactions in the Etiology of Childhood Cancer, the idea of a pooled analysis of birth weight and childhood leukemia was born. In a presentation entitled "The application of the life cycle paradigm to childhood cancer epidemiology", I discussed the relation of high birth weight to childhood ALL. Using the review by Ross (1996) that indicated an overall 2-fold increased risk of leukemia in children of high (> 4,000 g) compared to normal birthweight in 12 of the 16 studies, I reviewed the research since 1996. My talk extended the association to all but one of the recent studies (Westergaard T, 1997; Ross J,1997; Roman E,1997; Reynolds P, 2002), identified the potential for a similar association for AML and the potential for a greater magnitude of effect of birth weight in children who were diagnosed with cancer aged < 5 years versus those aged > 5 years. My talk ended with a description of the major determinants of birth weight, (Hennessey E, 1998) and examined the potential role of early childhood growth in the etiological pathway to ALL based on the research of Westergaard (1997) and of Broomhall (1983), that is similar to work in breast cancer (De Stavola B, 2000). I called for researchers to examine the effects of the leading determinants of birthweight on risk of childhood leukemia. During the meeting, Dr. Joachim Schuz and others indicated their interest in developing a collaboration to examine the role of birthweight in childhood leukemia by diagnostic subtypes as well as by other factors, because childhood ALL and AML are rare diseases with too few patients in a single study to perform the analysis of interest. Within the year the idea for a pooled analysis of this area had been fleshed out by Dr. Schuz and I, and an invitational letter was sent to potential collaborators. AimsThe aims of the pooled analysis of birthweight and childhood ALL and AML are to:1. Examine the association of birthweight to childhood leukemia by age at diagnosis and by diagnostic subtypes;2. Should a birthweight association appear, examine the influence of the major factors associated with birthweight and whether infant feeding or growth in early childhood modifies the relation.