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: 2630751
• 负责人: ANDREW OLSHAN
• 金额: $ 49.29万
• 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/2630751
• 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.

肾母细胞瘤是儿童最常见的肾脏肿瘤， 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， 环境的影响。 我们建议进行第一次大型的， 肾母细胞瘤危险因素的综合病例对照研究 的 拟议的研究将采用改进的方法， 测量和临床和生物标志物，以评估潜在的 基因-环境交互作用 将确定约800个病例 通过国家Wilms肿瘤研究小组（NWTSG），一个国家 参与了超过95%的病例的合作临床试验 在美国确诊的肾母细胞瘤 父母的情况下， 通过随机数字电话拨号识别800个对照，与 年龄和地理区域，将通过电话进行访谈。 一 这项研究的主要目的是评估特定父亲的作用， 职业和相关的暴露在以前的研究中被报告为风险 肾母细胞瘤的因素。 最一致的关联涉及到 父亲的职业，如焊工，机械师和机械师。 相关 在这些和其他职业中发现的暴露包括金属， 溶剂. 然而，对先前研究的解释一直是 受到一些方法论问题的阻碍。 拟定的研究将 克服这些限制，包括采用改进的 职业数据收集和接触评估方法。 的 这项研究还将评估妇女作为理发师就业情况， 电子制造工人、实验室工作人员和牙科医生 助剂和相关的染料暴露，电磁场， 溶剂和金属。这种对父母职业的评价应该 提供必要的证据，以证实或反驳以前的 调查结果。这项研究使用了一个最近开发的系统， 分支面试和工业企业家审查，以获得工作-和 具体的数据。 因为大多数病人的数据都是 作为正在进行的NWTS-5的一部分， 治疗和生物学研究，我们将分别分析暴露 对于由11 p，1 p， 16 q，诊断时的年龄，前驱病变，双侧性， 先天性异常 我们将能够定义子组， 潜在的新生生殖系突变，更可能是一种病因学途径 受到父亲先入为主的职业暴露的影响 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、住宅使用杀虫剂等怀孕条件 以及新生儿和儿童的状况。医疗记录 将对妊娠和分娩因素进行验证。 这 这项研究将为我们对Wilms的了解提供重要的新进展 考虑到研究规模、暴露评估质量和 病原学的临床和生物学标志物的结合 异质性