Environmental, lifestyle, and familial/ethnic factors associated with myeloproliferative neoplasms

Abstract

Myeloproliferative neoplasms (MPNs) are characterized by overproduction of mature functional blood cells and are often associated with an acquired genetic mutation of Janus Kinase 2 V617F . The etiology of MPNs remains unknown. The aim of this article was to review and collate all known published data investigating environmental and lifestyle factors associated with MPNs. Medline, Embase, PubMed, Cochrane, and Web of Science were systematically searched using terms for MPNs and observational study designs to identify studies investigating the risk factors for MPNs published before March 2010. Of 9,156 articles identified, 19 met the selection criteria. Although the studies exhibited heterogeneity, in case definitions, study design, and risk factors investigated, several themes emerged. A strong association was found with Jewish descent, and with a family history of MPNs. Autoimmune conditions, specifically Crohn's disease, were more common in patients with MPNs. Certain occupational groups were significantly associated with MPNs including occupations with potential exposure to benzene and/or petroleum. Blood donation was associated with an increased risk of polycythemia vera specifically. The vast heterogeneity in studies identified as part of this review suggests that large scale systematic assessment of etiological factors associated with MPNs is warranted. Am. J. Hematol. 87:175-182, 2012. V V C 2011 Wiley Periodicals, Inc. IntroductionMyeloproliferative neoplasms (MPNs) are a group of hematopoietic malignancies resulting from a transformed hematopoietic progenitor cell. They are characterized by overproduction of mature functional blood cells. MPNs were historically termed myeloproliferative disorders and have undergone numerous amendments in classification. The 2008 World Health Organisation MPN classification groups a number of related disorders including the classic MPNs polycythemia vera (PV), essential thrombocythemia (ET), and primary/idiopathic myelofibrosis (PMF) [1] which will be the focus of this review. Reported incidence rates vary from 0.02 to 2.8 per 100,000 persons [2]. However, incidence rates are not well characterized and half of all patients are asymptomatic at diagnosis [1]. PV and ET are indolent neoplasms with better prognosis (88% and 92% 3-year survival, respectively) compared to PMF which has a 63% 3-year survival in the United States [3].An acquired genetic mutation of Janus kinase 2 (JAK2) V617F is present in the majority of PV patients and in approximately half of patients with ET and PMF [4]. A recent study investigating JAK2 V617F mutations in 10,507 participants of the Copenhagen City Heart Study reported an incidence rate of 171 per 100,000 persons [5]. These participants had higher overall morbidity and mortality than those who were JAK2 V617F negative; however, 28% did not develop any malignancy during the 17.6-year follow-up [5] [12]. The population attributable risk of 46/1 JAK2 in PV patients has been estimated at 28%, explaining approximately 50% of the increased risk of...

JAK2V617F somatic mutation in the general population: myeloproliferative neoplasm development and progression rate

“…On the other hand, we are not aware of data suggesting that our results should not be applicable to all races, particularly as the JAK2V617F somatic mutation has been found in people from different races. 4,19,20 In conclusion, we demonstrate that increased JAK2V617F mutation burden is associated with myeloproliferative neoplasm progression rate in the general population. Furthermore, we established a JAK2V617F mutation burden cut-off point of 2% indicative of disease versus no disease.…”

Minor allele frequency of myeloproliferative neoplasm mutations in the Irish blood donor population

“…The varying allele frequencies for MPN mutations could account for the variability of incidence rates seen between populations of European ancestry, providing a better understanding of the genetic predisposition to MPNs. This variation may further indicate that underlying differences in allele frequencies in addition to other external lifestyle and occupational factors could account for aetiologic mechanisms of MPNs. Further investigation is needed to identify genetic variation of individuals in these populations who have subsequently developed an MPN to improve our understanding of these rare diseases.…”

Clinical utility gene card for: familial polycythaemia vera

“…An ethnic association is known for Jewish descent, particularly Ashkenazi (5.8% PV cases versus 3% in a reference population in France). 21 …”