Objectives The aetiology of a rare category of myeloproliferative neoplasms (MPN), bone marrow diseases with an excess of blood cells, is currently unknown. An MPN cluster in northeastern Pennsylvania allowed investigation of occupational risk factors and gene-environment interactions. Among our hypotheses were risks associated with aromatic and heterocyclic amines.
Methods This 2011 population-based case-control study assessed lifetime occupational, residential, smoking and dietary history by telephone interview. Cases (n = 55) were identified from the Pennsylvania cancer registry and a previous MPN study. Controls (n = 473) were selected based on eligibility screening using random digit dialling. People born from 1921−1968 and residing in 3 counties with high incidence of MPN were eligible. Blood samples for genotyping were collected from 31 cases and 292 controls.
Results Cases were older (median age = 71 vs 61yrs) and more likely to be male (49% vs 39%) compared to controls but otherwise demographically similar. Ever working in ten employment areas (welding, painting, degreasing, firefighting or working with glue, solvents/inks, pesticides, diesel equipment, animals, or X-rays/radioactive material at the 8 most recent jobs) were not associated with MPN.
In analyses that examined the main effects of over 50 environmentally sensitive genes, the presence of NAT2 slow acetylator genotype, GSTM1 gene deletion, and GSTA1, and GSTM3 variants were associated with an increased risk for MPNs (unadjusted ORs 2.1–3.2, 95% C. I.s excluding 1.0). Results were similar for analyses restricted to JAK2 positive cases.
Conclusions No relationship was found with occupations with presumed exposure to aromatic and heterocyclic amines, but our findings suggest that genotypes that modify the toxicity of these exposures may play a role in MPNs. Sources of exposures important to the pathway whereby NAT2 or other genotypes modify the effect of exposures in this population remain unclear and there is ongoing work on refining exposure assessment in the project.
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