The Role of Genotypes That Modify the Toxicity of Chemical Mutagens in the Risk for Myeloproliferative Neoplasms

Details

• Alternative Title:
  Int J Environ Res Public Health
• Personal Author:
  Gross-Davis, Carol Ann ; Heavner, Karyn ; Frank, Arthur L. ; Newschaffer, Craig ; Klotz, Judith ; Santella, Regina M. ; Burstyn, Igor
• Description:
  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.|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.|The presence of NAT2 slow acetylator genotype, and CYP1A2, GSTA1, and GSTM3 variants were associated with an average 3-5 fold increased risk.|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.
• Subjects:
  Article Candidate Gene Case-control Study Essential Thrombocythemia (ET) Mendelian Randomization Polycythemia Vera (PV) Primary Myelofibrosis (PMF)
• Source:
  Int J Environ Res Public Health. 2015; 12(3):2465-2485.
• Pubmed ID:
  25719551
• Pubmed Central ID:
  PMC4377912
• Document Type:
  Journal Article
• Funding:
  1R01EH000640-01/EH/NCEH CDC HHS/United States ; EH09-006E/EH/NCEH CDC HHS/United States ; ES009089/ES/NIEHS NIH HHS/United States
• Volume:
  12
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:9aba555ea1273d8dc23a0e7c9e499fb1a4d344be84646be6e826bb631c6703c5
• Download URL:
  https://stacks.cdc.gov/view/cdc/30744/cdc_30744_DS1.pdf
• File Type:
  [PDF - 700.56 KB ]