Low birth weight & other risk factors for hepatoblastoma

低出生体重

• 批准号: 7019995
• 负责人: Logan G. Spector
• 金额: $ 50.44万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-18 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7019995
• 关键词: age difference; cancer risk; children; clinical research; disease /therapy duration; gene environment interaction; gene expression; gene frequency; genetic polymorphism; genetic susceptibility; genomic imprinting; hepatoblastoma; human genetic material tag; human subject; insulinlike growth factor; interview; longitudinal human study; low birth weight infant human; maternal behavior; neoplasm /cancer diagnosis; neoplasm /cancer epidemiology; neoplasm /cancer genetics; occupational hazard; smoking

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.

描述（由申请人提供）：肝母细胞瘤（HB）是一种罕见的肝脏肿瘤，在美国，其发病率在1975年至1999年期间翻了一番。最近的证据表明，低出生体重（LBW：1，500 - 2，500克），特别是极低出生体重（VLBW：<1，500克）婴儿的HB风险增加。小规模（< 100例）病例对照研究也提示HB与母亲怀孕时吸烟、父母职业和髓过氧化物酶（MPO）基因多态性有关。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。我们将收集2000-2008年在美国儿童肿瘤学组织机构诊断的600例乙肝病例，其中约120例应为LBW和VLBW。对照组（480例正常出生体重; 120例LBW; 120例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进行频率匹配。将通过父母访谈收集暴露数据，并将收集颊细胞进行DNA分析;还将收集病例的肿瘤组织。我们的主要目标是：1）确定早产治疗的持续时间和强度是否增加LBW和VLBW婴儿中HB的风险，2）检查父母职业和母亲生活方式在HB风险中的作用，3）比较病例和对照中候选遗传易感性基因多态性的频率，4）比较病例和对照母亲中候选遗传易感性基因多态性的频率，5）描述HB病例中IGF-2基因印迹的模式，按年龄和出生体重。我们假设早产治疗是低出生体重儿的主要危险因素，其他外源性暴露在病因学上的重要性较小。我们进一步假设，激活和解毒毒素的能力的内源性决定因素是正常和低出生体重儿童的风险因素。