CASE CONTROL STUDY OF RISK FACTORS FOR WILMS TUMOR

肾母细胞瘤危险因素的病例对照研究

• 批准号: 2896147
• 负责人: ANDREW OLSHAN
• 金额: $ 57.3万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-10 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2896147
• 关键词: Wilms' tumor; cancer risk; case history; clinical research; disease /disorder etiology; environment related neoplasm /cancer; human subject; interview; loss of heterozygosity; neoplasm /cancer epidemiology; occupational hazard; parent offspring interaction; perinatal

Wilms tumor is the most common kidney tumor of childhood and has served as an important model for understanding the genetics and molecular biology of cancer. Epidemiologic studies have suggested but not proven an environmental influence. We propose to conduct the first large, comprehensive case-control study of risk factors for Wilms tumor. The proposed study will incorporate improved methods for exposure measurement and clinical and biologic markers to evaluate potential gene-environment interaction. About 800 cases will be identified through the National Wilms Tumor Study Group (NWTSG), a national collaborative clinical trial that enrolls over 95 percent of all cases of Wilms tumor diagnosed in the United States. Parents of cases and of 800 controls identified by random digit telephone dialing, matched to cases on age and geographic area, will be interviewed by telephone. A major aim of the study is to evaluate the role of specific paternal occupations and related exposures reported in previous studies as risk factors for Wilms tumor. The most consistent associations have involved paternal employment as welders, mechanics, and machinists. Related exposures found in these and other occupations include metals and solvents. However, the interpretation of previous studies has been hampered by a number of methodologic concerns. The proposed study will overcome these limitations, including the incorporation of improved methods for occupational data collection and exposure assessment. The study will also evaluate maternal employment as hairdressers, electronics manufacturing workers, laboratory workers, and dental assistants and related exposure to dyes, electromagnetic fields, solvents, and metals. This evaluation of parental occupation should provide the evidence necessary to either confirm or refute previous findings. The proposed study uses a recently developed system of branched interviews and industrial hygienist review to obtain job- and exposure-specific data. Since most of the patients have data collected on clinical and biologic markers as part of the ongoing NWTS-5 therapeutic and biology study, we will analyze the exposures separately for subgroups of patients defined by loss of heterozygosity at 11p, 1p, 16q, age at diagnosis, precursor lesions, bilaterality, and presence of congenital anomalies. We will be able to define subgroups with potential de novo germline mutations, an etiologic pathway more likely to be influenced by paternal preconceptional occupational exposures. We will also evaluate other suspected but unproved risk factors for Wilms tumor, such as residential use of pesticides, pregnancy conditions and exposures, and neonatal and childhood conditions. A medical records validation will be performed for pregnancy and delivery factors. This study will provide important new advances in our understanding of Wilms tumor given the study size, quality of exposure assessment, and incorporation of clinical and biological markers of etiologic heterogeneity.

肾母细胞瘤是儿童期最常见的肾肿瘤，已用于 作为理解遗传学和分子生物学的重要模型 癌症生物学。 流行病学研究表明但尚未证实 环境影响。 我们建议进行第一次大型、 肾母细胞瘤危险因素的综合病例对照研究。 这 拟议的研究将采用改进的暴露方法 测量以及临床和生物标志物来评估潜力 基因-环境相互作用。 将发现约800例病例 通过国家肾母细胞瘤研究组 (NWTSG) 合作临床试验招募了超过 95% 的病例 在美国诊断出肾母细胞瘤。 案件的家长和 800 个通过随机数字电话拨号识别的控件，与 有关年龄和地理区域的案件，将通过电话进行访谈。 一个 该研究的主要目的是评估特定父亲的作用 先前研究中报告为风险的职业和相关暴露 肾母细胞瘤的影响因素。 最一致的协会涉及 父亲担任焊工、机械师和机械师。 有关的 在这些职业和其他职业中发现的接触包括金属和 溶剂。 然而，之前研究的解释是 受到许多方法论问题的阻碍。 拟议的研究将 克服这些限制，包括采用改进的 职业数据收集和暴露评估的方法。 这 研究还将评估母亲作为美发师的就业情况， 电子制造工人、实验室工作人员和牙科人员 助手和相关的染料、电磁场暴露， 溶剂和金属。对父母职业的评估应该 提供必要的证据来证实或反驳先前的事实 发现。拟议的研究使用了最近开发的系统 分支面试和工业卫生员审查以获得工作和 特定于暴露的数据。 由于大多数患者已收集数据 作为正在进行的 NWTS-5 的一部分，研究临床和生物标志物 治疗和生物学研究，我们将分别分析暴露情况 对于由 11p、1p 杂合性丢失定义的患者亚组， 16q、诊断时年龄、前期病变、双侧性和存在 先天性异常。 我们将能够定义子组 潜在的从头种系突变，更有可能是一种病因途径 受父亲孕前职业暴露的影响。 我们还将评估其他可疑但未经证实的风险因素 肾母细胞瘤，如住宅使用农药、怀孕情况 和暴露，以及新生儿和儿童状况。一份病历 将对怀孕和分娩因素进行验证。 这 研究将为我们对威姆斯的理解提供重要的新进展 考虑到研究规模、暴露评估的质量和 结合病因学的临床和生物学标志物 异质性。