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The role of genotypes that modify the toxicity of chemical mutagens in the risk for myeloproliferative neoplasms
Journal article   Open access   Peer reviewed

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

Carol Ann Gross-Davis, Karyn Heavner, Arthur L Frank, Craig Newschaffer, Judith Klotz, Regina M Santella and Igor Burstyn
International journal of environmental research and public health, v 12(3), pp 2465-2485
24 Feb 2015
PMID: 25719551
url
https://doi.org/10.3390/ijerph120302465View
Published, Version of Record (VoR) Open

Abstract

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

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Collaboration types
Domestic collaboration
Web of Science research areas
Environmental Sciences
Public, Environmental & Occupational Health
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