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Int. J. Environ. Res. Public Health 2015, 12(3), 2465-2485; doi:10.3390/ijerph120302465

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

1
Environmental Protection Agency, Region 3, 1650 Arch Street, Philadelphia, PA 19103, USA
2
Department of Environmental and Occupational Health, Drexel University, Philadelphia, PA 19104, USA
3
Drexel Autism Institute, Drexel University, Philadelphia, PA 19104, USA
4
Department of Environmental Health Services, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Received: 5 January 2015 / Accepted: 12 February 2015 / Published: 24 February 2015
View Full-Text   |   Download PDF [701 KB, uploaded 24 February 2015]

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. View Full-Text
Keywords: case-control study; candidate gene; polycythemia vera (PV); essential thrombocythemia (ET); primary myelofibrosis (PMF); Mendelian randomization case-control study; candidate gene; polycythemia vera (PV); essential thrombocythemia (ET); primary myelofibrosis (PMF); Mendelian randomization
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Gross-Davis, C.A.; Heavner, K.; Frank, A.L.; Newschaffer, C.; Klotz, J.; Santella, R.M.; Burstyn, I. The Role of Genotypes That Modify the Toxicity of Chemical Mutagens in the Risk for Myeloproliferative Neoplasms. Int. J. Environ. Res. Public Health 2015, 12, 2465-2485.

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Int. J. Environ. Res. Public Health EISSN 1660-4601 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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