title: Community-acquired infections and their association with myeloid malignancies.
abstract: BACKGROUND
  Antigenic stimulation is a proposed aetiologic mechanism for many haematological malignancies. Limited evidence suggests that community-acquired infections may increase the risk of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). However, associations with other myeloid malignancies including chronic myeloid leukaemia (CML) and myeloproliferative neoplasms (MPNs) are unknown.
  
  
  METHODS
  Using the Surveillance, Epidemiology and End Result (SEER)-Medicare database, fourteen community-acquired infections were compared between myeloid malignancy patients [AML (n=8489), CML (n=3626) diagnosed 1992-2005; MDS (n=3072) and MPNs (n=2001) diagnosed 2001-2005; and controls (200,000 for AML/CML and 97,681 for MDS/MPN]. Odds ratios (ORs) and 95% confidence intervals were adjusted for gender, age and year of selection excluding infections diagnosed in the 13-month period prior to selection to reduce reverse causality.
  
  
  RESULTS
  Risk of AML and MDS respectively, were significantly associated with respiratory tract infections, bronchitis (ORs 1.20 [95% CI: 1.14-1.26], 1.25 [95% CI: 1.16-1.36]), influenza (ORs 1.16 [95% CI: 1.07-1.25], 1.29 [95% CI: 1.16-1.44]), pharyngitis (ORs 1.13 [95% CI: 1.06-1.21], 1.22 [95% CI: 1.11-1.35]), pneumonia (ORs 1.28 [95% CI: 1.21-1.36], 1.52 [95% CI: 1.40-1.66]), sinusitis (ORs 1.23 [95% CI: 1.16-1.30], 1.25 [95% CI: 1.15-1.36]) as was cystitis (ORs 1.13 [95% CI: 1.07-1.18], 1.26 [95% CI: 1.17-1.36]). Cellulitis (OR 1.51 [95% CI: 1.39-1.64]), herpes zoster (OR 1.31 [95% CI: 1.14-1.50]) and gastroenteritis (OR 1.38 [95% CI: 1.17-1.64]) were more common in MDS patients than controls. For CML, associations were limited to bronchitis (OR 1.21 [95% CI: 1.12-1.31]), pneumonia (OR 1.49 [95% CI: 1.37-1.62]), sinusitis (OR 1.19 [95% CI: 1.09-1.29]) and cellulitis (OR 1.43 [95% CI: 1.32-1.55]) following Bonferroni correction. Only cellulitis (OR 1.34 [95% CI: 1.21-1.49]) remained significant in MPN patients. Many infections remained elevated when more than 6 years of preceding claims data were excluded.
  
  
  CONCLUSIONS
  Common community-acquired infections may be important in the malignant transformation of the myeloid lineage. Differences in the aetiology of classic MPNs and other myeloid malignancies require further exploration.
authors.affiliation: Centre for Public Health, Institute of Clinical Sciences, Block B, Queens University Belfast, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland, United Kingdom.
authors.forename: Glen J
authors.initials: GJ
authors.lastname: Titmarsh
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom.
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: McMullin
authors.affiliation: Centre for Public Health, Institute of Clinical Sciences, Block B, Queens University Belfast, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland, United Kingdom.
authors.forename: Charlene M
authors.initials: CM
authors.lastname: McShane
authors.affiliation: Centre for Public Health, Institute of Clinical Sciences, Block B, Queens University Belfast, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland, United Kingdom.
authors.forename: Mike
authors.initials: M
authors.lastname: Clarke
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Shady Grove, Room 6E226, Bethesda, MD, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
authors.affiliation: Centre for Public Health, Institute of Clinical Sciences, Block B, Queens University Belfast, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland, United Kingdom. Electronic address: l.anderson@qub.ac.uk.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Anderson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017714:Community-Acquired Infections / Q000150:complications* / Q000453:epidemiology; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000453:epidemiology / Q000209:etiology; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000209:etiology; D008297:Male; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000209:etiology*; D009196:Myeloproliferative Disorders / Q000453:epidemiology / Q000209:etiology*; D018426:SEER Program
keywords: Infection; Myeloid Malignancy; SEER-Medicare