382 Occupational and genetic risk factors for myeloproliferative neoplasms (MPN): A case-control study
这项病例对照研究调查了美国宾夕法尼亚州东北部骨髓增殖性肿瘤（MPN）患者的职业暴露和基因变异，发现NAT2、GSTM1等基因型与风险增加有关，但未发现职业因素与疾病的直接关联。
<h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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 <i>NAT2</i> slow acetylator genotype, <i>GSTM1</i> gene deletion, and <i>GSTA1</i>, and <i>GSTM3</i> 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. <h3>Conclusions</h3> 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 <i>NAT2</i> 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.