Predictors of Adult Leukemia

成人白血病的预测因素

• 批准号: 6915457
• 负责人: Julie Ann Ross
• 金额: $ 52.78万
• 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: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915457
• 关键词: acute myelogenous leukemia; adult human (21+); agriculture; benzene; cancer risk; chemotherapy; chronic myelogenous leukemia; clinical research; environmental exposure; gene environment interaction; genetic polymorphism; genetic susceptibility; human genetic material tag; human population study; human subject; interview; ionizing radiation; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nonsteroidal antiinflammatory agent; obesity; pesticides; smoking; statistics /biometry

DESCRIPTION (provided by applicant): Each year in the U.S. approximately 33,000 individuals will be newly diagnosed with leukemia and 23,300 will die from the disease. Little is known about the etiology of adult leukemia. Minnesota has the highest incidence rate of adult leukemia in the continental United States. In this proposed population-based case control study in Minnesota, we will systematically examine environmental and genetic factors that may contribute to adult leukemia. Due to a concurrent study of chronic lymphocytic leukemia (CLL) in southern Minnesota, we will focus this study on myeloid leukemia including acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML). A total of 711 cases of incident adult myeloid leukemia and 711 frequency matched population controls will be enrolled. Questionnaire data through telephone interviews and mouthwash samples for genotyping will be obtained. We will evaluate risk factors for myeloid leukemia combined, separately for the two major groups enrolled and by morphologically and cytogenetically defined subgroups if feasible. In addition to evaluating risk factors such as cigarette smoking, occupational exposures to benzene and ionizing radiation, and prior chemotherapy treatments, we will investigate a) the role of non-steroidal anti-inflammatory drugs (NSAIDs) in risk of leukemia b) farming practices and related exposures in association with adult leukemia, c) obesity as a risk factor, and d) the role of genetic susceptibility genes including PON1, CYPs (2C9,3A4,2E1,2D6), GSTs (M1/T1), UGT1A6, PLA2, ODC, MDR1, MPO, NQ01, LEPR, and LEP. Based on our preliminary data, we hypothesize that frequent aspirin use (but not non-aspirin NSAID use) will be associated with a decreased risk of adult myeloid leukemia, particularly, AML. We also hypothesize that livestock farmers using animal insecticides will be at an increased risk (particularly, CML). We also expect that obesity will be more frequent among cases than controls. Further we hypothesize that genetic differences in the ability to metabolize NSAIDs, detoxify environmental toxins (including pesiticides, cigarette smoke) and metabolize leptin contributes to risk. Finally, we hypothesize that unfavorable genotypes, in combination with specific exposures, increase the risk of adult myeloid leukemia. The significance of this proposal, specifically with respect-to the identification of possible prevention strategies for adult AML, has important public health implications.

描述（由申请人提供）：在美国，每年大约有 33,000 人被新诊断出患有白血病，23,300 人将死于该疾病。人们对成人白血病的病因知之甚少。明尼苏达州是美国大陆成人白血病发病率最高的州。在这项拟议的明尼苏达州基于人群的病例对照研究中，我们将系统地检查可能导致成人白血病的环境和遗传因素。由于明尼苏达州南部正在进行慢性淋巴细胞白血病 (CLL) 的同时研究，我们将本研究重点关注髓系白血病，包括急性髓系白血病 (AML) 和慢性髓系白血病 (CML)。总共 711 例成人髓系白血病病例和 711 例频率匹配的人群对照将被纳入。将通过电话访谈和漱口水样本获得问卷数据以进行基因分型。我们将分别评估纳入的两个主要组以及形态学和细胞遗传学定义的亚组（如果可行）的髓系白血病组合危险因素。除了评估吸烟、职业接触苯和电离辐射以及既往化疗等危险因素外，我们还将调查 a) 非甾体抗炎药 (NSAID) 在白血病风险中的作用 b) 农业实践以及与成人白血病相关的相关暴露，c) 肥胖作为危险因素，以及 d) 遗传易感基因（包括 PON1、CYP）的作用(2C9、3A4、2E1、2D6)、GST (M1/T1)、UGT1A6、PLA2、ODC、MDR1、MPO、NQ01、LEPR 和 LEP。根据我们的初步数据，我们假设频繁使用阿司匹林（但不使用非阿司匹林 NSAID）会降低成人髓系白血病（特别是 AML）的风险。我们还假设使用动物杀虫剂的畜牧农民面临的风险会增加（特别是 CML）。我们还预计病例中肥胖的发生率将高于对照组。此外，我们假设代谢非甾体抗炎药、解毒环境毒素（包括杀虫剂、香烟烟雾）和代谢瘦素的能力的遗传差异会导致风险。 最后，我们假设不利的基因型与特定的暴露相结合，会增加成人髓系白血病的风险。该提案的重要性，特别是在确定成人 AML 的可能预防策略方面，具有重要的公共卫生意义。