Smoking is associated with increased risk of myeloproliferative neoplasms: A general population‐based cohort study

Abstract

BackgroundFormer studies on smoking as a risk factor for Philadelphia‐negative myeloproliferative neoplasms (MPNs) have mainly been carried out in women's cohorts and studies with various definitions of MPNs. Herein, we conducted a cohort study with register‐based follow‐up of a general population from Denmark, to validate and substantiate prior observations.MethodsIn the Danish Health Examination Survey cohort, we used the Cox proportional‐hazards model adjusted for age, sex, body mass index, and level of education, to calculate hazard ratios (HRs), to investigate, whether daily smokers or occasional/ex‐smokers had an increased risk of MPNs compared to never‐smokers.ResultsFrom the time of data collection (September 2007 to October 2008) until 1 January 2015, 70 individuals were diagnosed with MPNs among 75 896 study participants. Similar results were observed in both the age and sex adjusted analysis and the multivariable analysis. The multivariable HR of any MPN diagnosis for daily smokers was 2.5 (95% CI: 1.3‐5.0). For essential thrombocytosis, polycythemia vera, myelofibrosis, and MPN‐unclassified, the HRs were 1.8 (95% CI: 0.5‐5.8), 1.7 (95% CI: 0.5‐5.8), 4.3 (95% CI: 0.9‐19), and 6.2 (95% CI: 1.5‐25), respectively. Among occasional/ex‐smokers the corresponding HRs were 1.9 (95% CI: 1.1‐3.3), 1.5 (95% CI: 0.6‐3.7), 0.8 (95% CI: 0.3‐2.4), 0.9 (95% CI: 0.2‐4.4), and 6.2 (95% CI: 1.8‐21). Participants, who smoked >15 g/day, had an overall HR of 3.4 (95% CI: 1.4‐8.2) for any MPN diagnosis, while participants who smoked ≤15 g/day, had an overall HR of 2.1 (95% CI: 0.9‐4.7).ConclusionSmoking was associated with MPN development when comparing smokers and never‐smokers. Further studies investigating smoking in MPNs are warranted to substantiate our findings.

Do we care enough about the role of smoking in the etiology of polycythemia?

“…Due to this relationship, the role of COHgb in secondary polycythemia is an expected finding (4,22). In many studies, the association between increased COHgb levels and erythrocytosis in smokers was shown (22)(23)(24). Our results also support these knowledge.…”

Smoking, blood cells and myeloproliferative neoplasms: meta‐analysis and Mendelian randomization of 2·3 million people

“…Also, the description of MPN was not completely identical in the studies. Leal used the International Classification of Diseases 9 (ICD‐9) (Leal et al , ) and Pedersen ICD‐8 and ICD‐10 (Pedersen et al , ). Sørensen recruited MPN patients from a single institution based on WHO‐5 MPN criteria (Lindholm Sorensen & Hasselbalch, ).…”

“…None of the studies explicitly mentioned bone marrow pathology as part of the MPN diagnosis. Incidence rates (IR per 100 000 person‐years) of MPN varied across the follow‐up studies with an IR of 98 in Leal (Leal et al , ) with a median of 11 years of follow‐up (~8·9 annually per 100 000), an IR of 13 in Pedersen with a mean of 6·8 years of follow‐up (~1·9 annually per 100 000) (Pedersen et al , ), and an IR of 16 in Kroll with a mean of 10 years of follow‐up (~1·6 annually per 100 000) (Kroll et al , ). In comparison, a recent meta‐analysis reported an incidence rate of 2·6 annually per 100 000 for MPN (Titmarsh et al , ).…”

“…Toxic substances in tobacco are highly potent inflammatory stimuli and associated with tumorigenesis and clonal haematopoiesis (Hasselbalch, ). Smoking is associated with increased blood cells (Billimoria et al , ; Dotevall et al , ; Lowe et al , ; Parry et al , ; Smith et al , ; Wannamethee et al , ; Lao et al , ; Eisenga et al , ) (full list of references in Data S1) and MPN (Pasqualetti et al , ; Kroll et al , ; Leal et al , ; Lindholm Sorensen & Hasselbalch, ; Pedersen et al , ) in some but not all observational studies, likely due to differences in study size, effect size and direction, year published, sex and age distribution, geographical region, smoking status (current versus ex‐smoker), smoking duration, smoking intensity (heavy versus light) and ethnicity. Smoking and MPNs share several clinical and biochemical characteristics, including a high risk of thrombosis, partly explained by an elevated haematocrit and leukocytosis and in vivo leukocyte, platelet and endothelial activation (Hasselbalch, ).…”

Time for revival of the red blood cell count and red cell mass in the differential diagnosis between essential thrombocythemia and polycythemia vera?

“…In fact, in the general population the risk of thrombosis at elevated HCT values has previously been reported to be driven by smoking, 56 which has recently been associated with an increased risk of MPN. 57 The excess blood volume is even larger in PV-patients with hepatic vein thrombosis, 16 who often have a normal HCT due to an expanded plasma volume. 4 Importantly, the thrombosis risk in JAK2V617F positive "ET" patients will likely be markedly reduced simply due to normalization of the expanded RCM by phlebotomies.…”