Childhood Cancer Pooling Project

儿童期ALL是儿童中最主要的癌症形式，但其病因和风险因素在很大程度上仍不清楚。少数因素，如唐氏综合症、其他特殊的基因异常、与白血病兄弟姐妹同卵双胞胎的白血病、电离辐射暴露(宫内和出生后)，一直被认为与儿童ALL和急性髓细胞白血病(AML)有关；然而，这些情况只解释了一小部分病例(Robison L，1995年)。事实上，90%以上的儿童白血病病例缺乏可信的病因解释(Pui C-H，1995)。2002年3月，在国家癌症研究所召开了一次研讨会，以确定迫切的研究需求并促进协作的跨学科方法(Linet M，2003)。在NCI关于儿童癌症病因学中基因-环境相互作用的研讨会上，诞生了对出生体重和儿童白血病进行综合分析的想法。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项研究中的12项研究中，高出生体重(4,000克)的儿童患白血病的风险总体上是正常出生体重的2倍，我回顾了自1996年以来的研究。我的演讲将这种关联扩展到了最近的一项研究(Westgaard T，1997；Ross J，1997；Roman E，1997；Reynolds P，2002)，这些研究发现了与AML类似的关联的可能性，以及在5岁被诊断为癌症的儿童中，出生体重的影响可能比那些5岁的儿童更大。我的演讲最后描述了出生体重的主要决定因素(Hennessey E，1998)，并基于Westgaard(1997)和BroomHall(1983)的研究(类似于乳腺癌研究(De Stavola B，2000))，研究了儿童早期发育在ALL病因途径中的潜在作用。我呼吁研究人员研究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，他们有兴趣开展一项合作，根据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是罕见的疾病，在一项研究中患者太少，无法进行感兴趣的分析。不到一年，舒兹博士和我就提出了对这一领域进行综合分析的想法，并向潜在合作者发出了一封邀请信。目的出生体重与儿童急性淋巴细胞白血病和急性髓细胞白血病的合并分析的目的是：1.检验出生体重与儿童白血病诊断年龄和诊断亚型的关系；2.如果出现出生体重关联，检查与出生体重相关的主要因素的影响，以及婴儿早期喂养或成长是否改变了这种关系。

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.