title: Epidemiology of adult acute myeloid leukemia: Impact of exposures on clinical phenotypes and outcomes after therapy.
abstract: BACKGROUND
  An increased risk of adult myeloid leukemia (AML) has recently been associated with lifestyle and environmental exposures, including obesity, smoking, some over the counter medications, and rural/farm habitats in case control studies. The association of these exposures with AML cytogenetic categories, outcomes after therapy, and overall survival is unknown.
  
  
  METHODS
  Relevant exposures were evaluated in a cohort of 295 consecutive AML patients diagnosed and treated at Mayo Clinic in Florida and Arizona. Standard cytogenetic risk categories were applied and reviewed in a central cytogenetic laboratory. The association of epidemiologic exposures with cytogenetic risk, complete remission after therapy, and overall survival was evaluated using logistic and Cox regression models.
  
  
  RESULTS
  A significant association between obesity and intermediate-abnormal cytogenetics was identified (OR: 1.94, P=0.025). Similarly, those with secondary AML were more likely to have poor risk (OR: 2.55, P<0.001) and less likely to have intermediate normal (OR: 0.48, P=0.003) cytogenetics. In multivariate analysis, overall survival was improved for patients ≥ 60 years receiving intensive (RR: 0.21, P<0.001) and non-intensive therapy (RR: 0.40, P<0.001 compared to no treatment, and was lower for users of tobacco (RR 1.39, P=0.032), and those with poor risk cytogenetics (RR: 3.96, P=0.002) or poor performance status (RR: 1.69, P<0.001). Furthermore, an association between statin use at the time of diagnosis (OR: 2.89, P=0.016) and increased complete remission after intensive chemotherapy was identified, while prior solid organ transplantation was associated with significantly lower complete remission rate after therapy (OR: 0.10, P=0.035).
  
  
  CONCLUSIONS
  Our results provide evidence that specific epidemiologic exposures, including obesity, are significantly associated with unique AML cytogenetic risk categories and response to therapy. This supports a link between patient lifestyles, clinical exposures, and leukemogenesis.
authors.affiliation: Division of Hematology and Medical Oncology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, United States. Electronic address: finn.laura@mayo.edu.
authors.forename: Laura
authors.initials: L
authors.lastname: Finn
authors.affiliation: Division of Hematology and Medical Oncology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, United States. Electronic address: Sproat.Lisa@mayo.edu.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sproat
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, United States. Electronic address: Heckman.Michael@mayo.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Heckman
authors.affiliation: Division of Laboratory Medicine/Pathology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, United States. Electronic address: Jiang.Liuyan@mayo.edu.
authors.forename: Liuyan
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, United States. Electronic address: Diehl.Nancy@mayo.edu.
authors.forename: Nancy N
authors.initials: NN
authors.lastname: Diehl
authors.affiliation: Division of Laboratory Medicine/Pathology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, United States. Electronic address: Ketterling.Rhett@mayo.edu.
authors.forename: Rhett
authors.initials: R
authors.lastname: Ketterling
authors.affiliation: Division of Hematology and Medical Oncology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, United States. Electronic address: Tibes.Raoul@mayo.edu.
authors.forename: Raoul
authors.initials: R
authors.lastname: Tibes
authors.affiliation: Division of Laboratory Medicine/Pathology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, United States. Electronic address: rvaldez@miracals.com.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Valdez
authors.affiliation: Division of Hematology and Medical Oncology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, United States. Electronic address: Foran.James@mayo.edu.
authors.forename: James
authors.initials: J
authors.lastname: Foran
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005431:Florida; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D008019:Life Style; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000150:complications*; D010641:Phenotype; D016016:Proportional Hazards Models; D012306:Risk; D016896:Treatment Outcome
keywords: Acute myeloid leukemia; Cytogenetics; Epidemiology