Anthropometric, medical history and lifestyle risk factors for myeloproliferative neoplasms in The Iowa Women's Health Study cohort

Myeloproliferative neoplasms (MPN), previously called myeloproliferative disorders (MPD), are a collective group of hematopoietic malignancies, which are categorized by a clonal expansion of terminally differentiated myeloid cells within the peripheral blood. Within this group of malignancies, essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) are collectively classified as classical MPN. These malignancies arise from a single mutated progenitor cell, with the most common mutation being a gain-of-function mutation within the Janus kinase 2 (JAK2) gene.1 Epidemiological studies have found JAK2 mutations to be present in nearly all cases of PV and approximately half of all cases of ET and MF.1, 2 There have been numerous additional studies that have discovered other mutations within patients with MPN that may play a role in their development, although the underlying pathogenesis of these malignancies is largely unknown. Although there is growing knowledge regarding the role that these mutations have in MPN, there are few data available regarding other risk factors that may be involved in their development. Ashkenazi Jewish descent was associated with higher risk of MPN3 and PV,4 and a family history of MPN is also a risk factor.4–7 The role of occupation and chemical exposure has been evaluated, with a few studies suggesting benzene as a possible risk factor for MPN development.8, 9 There are only limited data available regarding lifestyle and medical factors that may play a role in MPN development. In a large cohort of study of 1.3 million middle-aged women in the U.K., Kroll et al10 found that frequent smokers (defined as ≥15 cigarettes per day) were at increased risk of myeloproliferative/myelodysplastic disease combined, while there was no association with alcohol use; results specific to MPN were not reported. Kristinsson et al11 conducted a large record linkage study of 11,039 population-based cases of MPN, and found that prior history of an autoimmune disease was associated with an increased risk for MPN development. In contrast, Anderson et al12 conducted a case-control study consisting of 13,846 myeloid malignancy patients (1,017 of which had chronic myeloproliferative disease (MPD)) and found that overall, autoimmune conditions were not associated with risk of MPD. Given the limited data on risk factors for MPN, we investigated the role of medical, lifestyle and anthropometric factors in the development of MPN in a large, prospective cohort of Iowa women. In a secondary analysis, we also evaluated etiologic heterogeneity for the two most common MPN subtypes, ET and PV.