Smoking Ups Risk of Myeloproliferative Neoplasms Overall and by Subtype

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Smoking is associated with several inflammatory components and blood cell indices also typical in Philadelphia-negative chronic MPNs.
Smoking is associated with several inflammatory components and blood cell indices also typical in Philadelphia-negative chronic MPNs.

In a comparison study of smokers and never-smokers, smoking was associated with a greater risk of developing myeloproliferative neoplasms (MPNs), a study published in Cancer Medicine has shown.

Smoking is associated with several inflammatory components and blood cell indices also typical in Philadelphia-negative chronic MPNs — such as essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF), and unclassifiable MPNs (MPN-U). Patients with MPNs and smokers have an increased inflammatory burden, factors of which are known to be involved in tumor development and cancer progression. These similarities suggest that smoking may be a stimuli that potentially triggers and drives the MPN-clone.

Previous studies linking smoking with MPNs were conducted in women's cohorts and with various definitions of MPNs. For this study, researchers conducted a cohort study with register-based follow-up of selected people from the general population from Denmark in an effort to verify previous observations.

Using data from the Danish Health Examination Survey (DANHES), a population-based study conducted from September 2007 to October 2008, the researchers followed up with everyone from baseline until MPN diagnosis, loss to follow-up, death, or end of follow-up at January 1, 2015. Participants in DANHES were 18 to 99 years old and lived in 13 of the 98 municipalities in Denmark. They had been invited to complete 2 Internet-based questionnaires; one asked questions on basic demographics, health behavior including smoking, self-reported health, and living conditions, and a supplement questionnaire queried participants on diet.

Smoking status was reported as never, daily, current but not daily (ie, at least once per week but not daily, once per month, or rarer than once per month), and former smoking; and categorized as never-smokers, occasional smokers (combined current non-daily and ex-smokers), and daily smokers. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using Cox proportional-hazards models with delayed entry.

The final analysis included 75,896 study participants: 45,030 (59.7%) women, median age 49 years; and 30,866 (40.7%) men, median age 52.8 years. A total of 70 new cases of MPNs were diagnosed in participants during follow-up (41 in women, 29 in men). MPN diagnoses were 23 ET, 17 PV, 10 MF, and 27 MPN-U. Median age at diagnosis was 63.0 years.

Both age and sex adjusted and multivariable analyses results were similar. The multivariable HR of any MPN diagnosis during the study period was 2.5 (95% CI, 1.3-5.0) for daily smokers and 1.9 (95% CI, 1.1-3.3) for occasional/ex-smokers, compared with never smokers. HR for daily smokers and occasional/ex-smokers, respectively, by MPN subtype were 1.8 and 1.5 for a diagnosis of essential thrombocythemia; 1.7 and 0.8 for polycythemia vera; 4.3 and 0.9 for myelofibrosis; and 6.2 and 6.2 for MPN-U.

These results demonstrate a higher risk of developing any MPN among smokers compared with never-smokers. “The results of this study support the growing evidence suggesting smoking to be a risk factor in the development of MPNs,” the researchers conclude.


Pedersen KM, Bak M, Sørenson AL, et al. Smoking is associated with increased risk of myeloproliferative neoplasms: a general population-based cohort study [published online October 14, 2018]. Cancer Med. doi: 10.1002/cam4.1815

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