Molecular Epidemiology of Acute Myelogenous Leukemia

Little is known about the epidemiologic risk factors associated with the development of acute myelogenous leukemia (AML), and less is known about the role that genetic susceptibility plays in the development of AML. We propose to conduct a population-based study to investigate genetic susceptibility in adult AML patients, both de novo and treatment-related in a well-defined geographical area. Using a case-control design, we will prospectively enroll 400 patients from Texas and 800 healthy controls. Controls will be recruited using random digit dialing, and will be matched to the cases by age, gender, and ethnicity. Epidemiological and demographic information will be obtained through personal interviews, and will be integrated with clinical information, cytogenetic data, and genotypic markers. Blood specimens will be collected on all participants, who will be genotyped for markers associated with activation and detoxification of chemical carcinogens, including chemotherapy drugs. Polymorphisms in genes such as cytochrome p450 (CYP2E1), glutathione S-transferases (GSTT1, GSTM1, GSTP1), epoxide hydrolase (HYL1), NADPH-quinone oxidoreductase (NQO1), and myeloperoxidase (MPO) will be analyzed.

This study will provide insight into the role that these susceptibility markers, along with clinical epidemiological, and cytogenetic factors, play in the identification of people at risk of developing AML. Understanding how genetic predisposition and exogenous exposures interact to determine AML susceptibility will allow the development of prevention strategies in the future.