Myelodysplastic syndrome (MDS) is a heterogeneous disruption of the hematopoietic system that can lead to the development of acute myeloid leukemia (AML) in about 1/3 of cases. MDS became reportable to the Surveillance, Epidemiology and End Results program in 2001. It is estimated that about 10,000 MDS cases are newly diagnosed each year in the United States, which is similar to the number of malignant gliomas. Minnesota has one of the higher incidence rates of MDS. With the exception of chemotherapy and radiation treatment for other cancers, which is associated with <5% of MDS, little is known about causes. Of the few studies conducted (mostly <200 cases and/or clinic-based), there is a suggestion of a role for occupational exposures, cigarette smoking, and some other lifestyle factors, many of which are similar to those associated with AML. We are proposing a new population-based study of MDS in Minnesota that utilizes the questionnaire and infrastructure of our ongoing adult myeloid leukemia study that concludes in early 2010. A total of 705 MDS cases and 705 frequency-matched population controls will be enrolled over a 4 1/2 year period (April 1, 2010 - October 31, 2014). In addition to evaluating potential risk factors such as those described above, we will explore risk factors by central pathology reviewed subtypes of MDS by integrating data from our adult myeloid leukemia study. We will also determine those environmental or other exogenous risk factors that are common to AML and MDS versus those risk factors that are distinct. Additionally, we will explore whether there are risk factors more common to MDS cases that are at risk of progressing to AML, which includes the novel incorporation of prognostic scoring systems. Finally, we will collect saliva from MDS cases and controls for future genetic susceptibility studies. This study will be the largest population-based study of MDS conducted to date. With the incorporation of a successful infrastructure, and the ability to make comparisons with a similar existing study of myeloid leukemia, we are uniquely positioned to answer important etiological questions regarding MDS. The significance of this proposal also relates to potential prevention strategies for adult AML, which has important public health implications. Public Health Relevance: Myelodysplastic syndrome (MDS) is a blood cancer that affects about 10,000 people in the United States each year. Little is known about why MDS happens or why some people with MDS eventually develop leukemia. We are proposing one of the largest epidemiological studies of MDS ever conducted, with the goal of being able to identify risk factors that could lead to prevention.