title: The role of genotypes that modify the toxicity of chemical mutagens in the risk for myeloproliferative neoplasms.
abstract: BACKGROUND
  The etiology of myeloproliferative neoplasms (MPN) (polycythemia vera; essential thrombocythemia; primary myelofibrosis) is unknown, however they are associated with a somatic mutation--JAK2 V617F--suggesting a potential role for environmental mutagens.
  
  
  METHODS
  We conducted a population-based case-control study in three rural Pennsylvania counties of persons born 1921-1968 and residing in the area between 2000-2008. Twenty seven MPN cases and 292 controls were recruited through random digit dialing. Subjects were genotyped and odds ratios estimated for a select set of polymorphisms in environmentally sensitive genes that might implicate specific environmental mutagens if found to be associated with a disease.
  
  
  RESULTS
  The presence of NAT2 slow acetylator genotype, and CYP1A2, GSTA1, and GSTM3 variants were associated with an average 3-5 fold increased risk.
  
  
  CONCLUSIONS
  Exposures, such as to aromatic compounds, whose toxicity is modified by genotypes associated with outcome in our analysis may play a role in the environmental etiology of MPNs.
authors.affiliation: Environmental Protection Agency, Region 3, 1650 Arch Street, Philadelphia, PA 19103, USA. gross-davis.carolann@epa.gov.|Department of Environmental and Occupational Health, Drexel University, Philadelphia, PA 19104, USA. gross-davis.carolann@epa.gov.
authors.forename: Carol Ann
authors.initials: CA
authors.lastname: Gross-Davis
authors.affiliation: Department of Environmental and Occupational Health, Drexel University, Philadelphia, PA 19104, USA. karynkh@aol.com.
authors.forename: Karyn
authors.initials: K
authors.lastname: Heavner
authors.affiliation: Department of Environmental and Occupational Health, Drexel University, Philadelphia, PA 19104, USA. alf26@drexel.edu.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Frank
authors.affiliation: Drexel Autism Institute, Drexel University, Philadelphia, PA 19104, USA. cnewscha@drexel.edu.
authors.forename: Craig
authors.initials: C
authors.lastname: Newschaffer
authors.affiliation: Department of Environmental and Occupational Health, Drexel University, Philadelphia, PA 19104, USA. judith.klotz@comcast.net.
authors.forename: Judith
authors.initials: J
authors.lastname: Klotz
authors.affiliation: Department of Environmental Health Services, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. rps1@cumc.columbia.edu.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.affiliation: Department of Environmental and Occupational Health, Drexel University, Philadelphia, PA 19104, USA. cnewscha@drexel.edu.|Drexel Autism Institute, Drexel University, Philadelphia, PA 19104, USA. cnewscha@drexel.edu.
authors.forename: Igor
authors.initials: I
authors.lastname: Burstyn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004781:Environmental Exposure; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D009196:Myeloproliferative Disorders / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D010414:Pennsylvania / Q000453:epidemiology; D011087:Polycythemia Vera / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D011110:Polymorphism, Genetic; D055728:Primary Myelofibrosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000453:epidemiology / Q000209:etiology / Q000235:genetics
chemical_list: D009153:Mutagens