Germline Genetics of Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

Myelodysplastic syndromes (MDS) are part of a heterogeneous and overlapping group of clonal diseases that arise in the hematopoietic stem or progenitor cells and also include acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and the hybrid MDS/MPN entities. Individuals with MDS have a high risk of progressing to leukemia, with approximately 30% expected to develop AML. This study evaluates genetic susceptibility to myeloid malignancy using data from population-based case control studies of myelodysplastic syndromes and acute myeloid leukemia in adults (ages 18-85 years) and pediatric MDS cases with banked samples at the Center for International Blood and Marrow Transplant Research (CIBMTR). Adult cases were identified through the Minnesota Cancer Reporting System and controls were recruited from the State Driver's License/Identification Card list. DNA samples were collected via mouthwash collection kits (AML cases and controls) or Oragene saliva collection kits (adult MDS cases and controls). Pediatric MDS samples were banked at CIBMTR prior to receipt of a transplant and DNA was extracted from isolated T cells or whole blood samples. Genotyping data were generated using the Illumina Global Diversity array and quality control and genotype calling was conducted using established best practices. Our primary analyses investigated the contribution of genetic variation to MDS risk and evaluated the role of the killer cell immunoglobulin receptors (KIR) on incidence and survival.]]>
Adult MDS Cases: Inclusion: Diagnosed with MDS (ICD-O-3 codes: 9980, 9982-9987, 9989) between April 1, 2010 and October 31, 2014 identified by the Minnesota Cancer Surveillance system, residing in Minnesota, ages 20-85, and could understand English or Spanish. AML Cases: Inclusion: Diagnosed with AML (ICD-O-3 codes: 9840, 9861, 9866-9867, 9871-9897, 9910, 9920) between June 1, 2005 and November 30, 2009 identified by the Minnesota Cancer Surveillance system, residing in Minnesota, ages 20-79, and could understand English or Spanish. Controls: Inclusion: Live at time of recruitment, residing in Minnesota, ages 20-85, and could understand English or Spanish. Exclusion: Prior diagnosis of myeloid leukemia or MDS.Pediatric MDS Cases: Inclusion: Received transplant for MDS, age 0-19 years. Exclusion: Prior receipt of HSCT ]]>