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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: The role of genotypes that modify the toxicity of chemical mutagens in the risk for myeloproliferative neoplasms.

Authors: Gross-Davis, Carol Ann; Heavner, Karyn; Frank, Arthur L; Newschaffer, Craig; Klotz, Judith; Santella, Regina M; Burstyn, Igor

Published In Int J Environ Res Public Health, (2015 Feb 24)

Abstract: 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.

PubMed ID: 25719551 Exiting the NIEHS site

MeSH Terms: Adult; Aged; Aged, 80 and over; Case-Control Studies; Environmental Exposure*; Female; Gene-Environment Interaction; Genotype*; Humans; Male; Middle Aged; Mutagens/toxicity*; Myeloproliferative Disorders/epidemiology*; Myeloproliferative Disorders/etiology; Myeloproliferative Disorders/genetics; Neoplasms/epidemiology*; Neoplasms/etiology; Neoplasms/genetics; Pennsylvania/epidemiology; Polycythemia Vera/epidemiology; Polycythemia Vera/etiology; Polycythemia Vera/genetics; Polymorphism, Genetic; Primary Myelofibrosis/epidemiology; Primary Myelofibrosis/etiology; Primary Myelofibrosis/genetics; Risk Factors; Thrombocythemia, Essential/epidemiology; Thrombocythemia, Essential/etiology; Thrombocythemia, Essential/genetics

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