title: Familial aggregation of acute myeloid leukemia and myelodysplastic syndromes.
abstract: OBJECTIVE
  Apart from rare pedigrees with multiple cases of acute myeloid leukemia (AML), there is limited data on familial aggregation of AML and myelodysplastic syndromes (MDSs) in the population.
  
  
  METHODS
  Swedish population-based registry data were used to evaluate risk of AML, MDS, and other malignancies among 24,573 first-degree relatives of 6,962 patients with AML and 1,388 patients with MDS compared with 106,224 first-degree relatives of matched controls. We used a marginal survival model to calculate familial aggregation.
  
  
  RESULTS
  AML and/or MDS did not aggregate significantly in relatives of patients with AML. There was a modest risk ratio (RR, 1.3; 95% CI, 0.9 to 1.8) in myeloproliferative/myeloid malignancies combined. The risks for any hematologic or any solid tumor were modestly but significantly increased. Relatives of patients with MDS did not show an increased risk for any hematologic tumors. In contrast, we found a significantly increased risk (RR, 6.5; 95% CI, 1.1 to 38.0) of AML/MDS and of all myeloid malignancies combined (RR, 3.1; 95% CI, 1.0 to 9.8) among relatives of patients diagnosed at younger than age 21 years.
  
  
  CONCLUSIONS
  We did not find evidence for familial aggregation of the severe end of the spectrum of myeloid malignancies (AML and MDS). The risks of myeloproliferative neoplasms were modestly increased with trends toward significance, suggesting a possible role of inheritance. In contrast, although limited in sample size, relatives of young patients with AML were at increased risk of AML/MDS, suggesting that germline genes may play a stronger role in these patients. The increased risk of all hematologic malignancies and of solid tumors among relatives of patients with AML suggests that genes for malignancy in general and/or other environmental factors may be shared.
authors.affiliation: Genetic Epidemiology Branch, DCEG, NCI, 6120 Executive Blvd, Room 7124, MSC 7236, Bethesda, MD 20892-7236, USA. goldinl@mail.nih.gov
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Goldin
authors.forename: Sigurdur Y
authors.initials: SY
authors.lastname: Kristinsson
authors.forename: Xueying Sharon
authors.initials: XS
authors.lastname: Liang
authors.forename: Asa R
authors.initials: AR
authors.lastname: Derolf
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
mesh_terms: D000368:Aged; D005192:Family Health; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology