Rare Disease Report

Daily Smokers Have a More than 3 Times Increased Risk for MPN

NOVEMBER 28, 2018
Einav Keet
The results of a new study conducted by investigators in Denmark suggest that smoking may be a risk factor for the development of myeloproliferative neoplasms (MPN), a rare group of blood cancers.

Chronic myeloproliferative disorders are rare, slow-growing blood cancers that occur when either red blood cells, white blood cells, or platelets accumulate in the blood from overproduction in the bone marrow. In some cases, the body may make too much of more than 1 type of blood cell, and some patients can develop acute myeloid leukemia.

The types of myeloproliferative disorders include chronic myelogenous leukemia, polycythemia vera, primary myelofibrosis, essential thrombocythemia, chronic neutrophilic leukemia, and chronic eosinophilic leukemia. The cause of these illnesses remains unknown, though the development of MPNs may be due to environmental and genetic factors, such as radiation exposure and a mutation in the JAK2 gene.

Studies have also identified an association between smoking and the development of MPNs, with cigarette smoking leading to a chronic inflammatory state driving clonal evolution and disease progression. A new multi-institutional study led by University of Copenhagen investigators and published in the journal Cancer Medicine, aimed to validate and substantiate previous findings on the link between smoking and Philadelphia chromosome-negative MPN cases with an activating JAK2 or MPL gene mutation.

Using data from The Danish Health Examination Survey, a population-based study, the research team looked at the responses from 75,896 Danish citizens from 2 internet‐based questionnaires collected between September 2007 and October 2008. This included a basic questionnaire with questions on sociodemographic and health behavior, such as smoking status, self‐reported health, and living conditions, as well as a supplementary questionnaire concerning diet.

Based on the responses, the investigators categorized participants as individuals who never smoked (never-smokers), occasional or ex-smokers, or daily smokers. During the follow-up period, 70 survey respondents developed MPNs, including 41 women and 29 men with a median age of 63. The overall MPN case count included 23 cases of essential thrombocythemia, 17 cases of polycythemia vera, 10 cases of myelofibrosis, and 27 cases of unclassifiable MPN.

Of these MPN cases in study participants, 20 occurred in never-smokers, 35 in occasional or ex-smokers, and 15 in daily smokers. The study team determined that daily smokers had a 2.5 times higher risk of developing MPN than never smokers, and occasional and ex-smokers had a 1.9 times higher risk. Smokers who consumed more than 15 grams per day were 3.4 times more likely to develop any MPN, while those who consumed 15 grams or less were 2.1 times more likely.

In an interview with Rare Disease Report®, first author Kasper M. Pedersen, MD, explained that prior studies on the relationship between smoking and MPN have been carried out in small-scale, case-control studies and large prospective women’s cohorts. “In contrast, we followed a large sample of both women and men from the Danish general population and to this date, with 75,896 individuals, it is the largest cohort study specifically aimed at investigating smoking and the risk of Philadelphia-negative MPN,” Dr. Pedersen said.

“Another difference is that we only included cases of Philadelphia-negative MPN, whereas some, not all, of the prior studies have used different definitions of MPN as they either omitted some Philadelphia-negative MPNs or included other myeloproliferative disorders in their analyses—eg, myelodysplastic disorder and chronic myelogenous leukemia.”

Dr. Pedersen added that the research team hopes to further study the causal pathway between smoking and MPN.

“The association between smoking and MPN certainly deserves further investigation,” he said. “In this context, it is important to keep in mind that these traditional epidemiological studies cannot determine causality and that they are prone to certain limitations, such as residual confounding and reverse causality. We plan to carry out further large-scale studies examining the possible detrimental role of smoking in the development of MPN.”

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