Low birth weight & other risk factors for hepatoblastoma

描述(申请人提供)：肝母细胞瘤(HB)是一种罕见的肝脏肿瘤，其发病率在1975年至1999年在美国翻了一番。最近的证据表明，低出生体重(LBW：1,500-2,500克)和特别低(VLBW：&lt；1,500克)出生体重的婴儿患HB的风险增加。小型(100例)病例对照研究也表明，乙肝与母亲怀孕期间吸烟、父母职业以及髓过氧化物酶(MPO)基因的多态有关。我们建议进行迄今为止规模最大、最全面的肝母细胞瘤病例对照研究。我们收集了2000-2008年在美国儿童肿瘤组织机构诊断的600例HB病例，其中大约120例应该是LBW和VLBW。对照组(480名正常出生体重；120名LBW；120名VLBW)将从美国出生登记处选择，并将在出生体重、性别、出生年份和诊断地区方面进行频率匹配。暴露数据将通过父母访谈收集，口腔细胞将被收集用于DNA分析；病例还将被收集其肿瘤组织。我们的主要目的是：1)确定早产儿的治疗时间和强度是否会增加LBW和VLBW婴儿患HB的风险；2)检查父母的职业和怀孕期间母亲的生活方式在HB风险中的作用；3)比较病例和对照中候选遗传易感基因多态的频率；4)比较病例和对照母亲中候选遗传易感基因多态的频率；5)描述HB病例中IGF-2基因印迹的模式，包括年龄和出生体重。我们假设早产儿的治疗是低出生体重儿的主要危险因素，其他外源性暴露是次要的病因。我们进一步假设，激活和排毒能力的内源性决定因素是正常出生体重和低出生体重儿童的危险因素。

DESCRIPTION (provided by applicant): Hepatoblastoma (HB) is a rare liver tumor, the incidence rate of which doubled between 1975 and 1999 in the U.S. Recent evidence suggests increased risk of HB in low (LBW: 1,500-2,500 grams), and especially very low (VLBW: <1,500 grams) birth weight infants. Small (< 100 cases) casecontrol studies have also suggested associations of HB with maternal smoking while pregnant,parental occupation, and a polymorphism in the myeloperoxidase (MPO) gene. We propose to conduct the largest and most comprehensive case-control study of hepatoblastoma to date. We will collect 600 cases of HB diagnosed at U.S, Children's Oncology Group institutions in 2000-2008,about 120 of whom should be LBW and VLBW. Controls (480 normal birth weight; 120 LBW; 120 VLBW) will be selected from United States birth registries and will be frequency matched on birth weight, sex, year of birth, and region of diagnosis. Exposure data will be collected through parental interview and buccal cells will be collected for DNA analysis; cases will also have their tumor tissue collected. Our primary aims are to: 1) Determine whether duration and intensity of treatment for prematurity increases risk of HB among LBW and VLBW infants, 2) Examine the role of parental occupation and maternal lifestyle while pregnant in the risk of HB, 3) Compare the frequency of candidate genetic susceptibility gene polymorphisms in cases and controls, 4) Compare the frequency of candidate genetic susceptibility gene polymorphisms in the mothers of cases and controls, 5) Describe the pattern of IGF-2 gene imprinting in HB cases in toto, by age, and by birthweight. We hypothesize that treatment for prematurity is the major risk factor among low birth weight children and that the other exogenous exposures are of minor etiologic importance. We further hypothesize that endogenous determinants of the ability to activate and detoxify toxins are risk factors among children with both normal and low birth weight.