ENVIRONMENTAL EXPOSURES AND RISK FOR ACUTE LEUKEMIA AND MYELODYSPLASIA IN ADULTS

工作总结：尽管数据尚未 在我们的病例对照研究中对该病的危险因素进行了深入分析 急性白血病和骨髓增生异常综合征，几乎没有 此项目在本财年的活动。在过去，我们有 吸烟与特定细胞遗传学之间已证实的关联 第二个病例组的急性髓系白血病的异常。在……里面 此外，我们已经完成了对风险因素的分析 骨髓增生异常综合征--一组血液系统疾病 在老年人中的重要性日益增加。在我们对158人的研究中 成人骨髓发育不良与人口控制、吸烟和 染发剂的使用与风险增加有关。职业 暴露也与MDS有关，包括石油。 馏分、卤化溶剂、焊接烟尘等试剂。在……里面 相比之下，这些因素与非急性髓系白血病无关 除非是特殊的染色体，否则会出现骨髓发育不良 出现了异常情况。这些结果表明， 骨髓发育不良可能是急性髓系白血病化学暴露的一个标志。我们 正在继续探索影响基因的作用 特定致癌物的代谢。我们之前已经证明了 谷胱甘肽-S-转移酶零基因携带者 Theta基因罹患骨髓增生异常的几率是后者的四倍 带有该基因的人的症状，尽管不清楚 暴露-基因相互作用已经确定，现在正在探索 其他基因的作用。我们还试图复制我们的 Ras基因强相关性的初步发现 急性髓系白血病和溶剂暴露的突变。然而，在一个 更大的患者样本并不能证实这一观察结果。规划 对这些疾病进行新的分子和流行病学研究 而活跃的数据分析将在99财年恢复。

Summary of work: Although data have not been thoroughly analyzed in our case-control study of risk factors for the acute leukemias and the myelodysplastic syndromes, there was little activity on this project in the current FY. In the past, we have confirmed associations between smoking and specific cytogenetic abnormalities in acute myeloid leukemia in a second case group. In addition, we have completed our analysis of risk factors for the myelodysplastic syndromes, a collection of hematologic disorders of increasing importance among the elderly. In our study of 158 adults with myelodysplasia and population controls, smoking and hair dye use were associated with increased risk. Occupational exposures were also associated with MDS, including petroleum distillates, halogenated solvents, welding fumes and other agents. In contrast, these factors were not associated with AML that was not preceded by myelodysplasia unless specific chromosome abnormalities were present. These results suggest that myelodysplasia may be a marker of chemical exposure in AML. We are continuing to explore the role of genes that affect the metabolism of specific carcinogens. We previously showed that persons with the null genotype of the glutathione-S-transferase theta gene had four times the odds of developing myelodysplastic syndromes as persons with the gene, although no clear exposure-gene interactions were identified and are now exploring the role of other genes. We have also attempted to replicate our preliminary finding of a strong association between ras gene mutations in AML and solvent exposure. However, results on a larger sample of patients do not confirm this observation. Planning for new molecular and epidemiologic studies of these conditions and active data analysis will resume in FY 99.