Dr Sekeres on Next Steps for Evaluating the Association Between Smoking and MDS

“MDS is a cancer [with] a multi-step genetic process. Patients, on average, have 3 or 4 driver mutations that they acquire before their first diagnosis with MDS. If a person smokes at discrete stages of his or her life, do they have different types of mutations that they’re introducing into that time course?”

Mikkael A. Sekeres, MD, a professor of medicine and chief of the Division of Hematology in the Leukemia Section at the University of Miami Health System and Sylvester Comprehensive Cancer Center, discussed potential future directions for assessing ways that tobacco smoking may be linked to genetic drivers of myelodysplastic syndrome (MDS) disease progression.

Sekeres and colleagues conducted a prospective cohort study evaluating the association between smoking intensity/duration and the number/types of genetic mutations present in patients diagnosed with MDS beginning in June 2016. A univariate analysis showed that smokers and nonsmokers had similar numbers of mutations overall, as well as within distinct disease groups, including idiopathic cytopenia of undetermined significance, clonal cytopenia of undetermined significance, MDS, MDS/myeloproliferative neoplasm overlap syndrome, and acute myeloid leukemia. However, mutation prevalence was higher among smokers compared with nonsmokers.

Potential future next steps with this research include continued efforts to characterize the association between smoking and the development of genetic mutations, as well as determining the time point at which smoking generates new mutations in a patient’s overall MDS disease course, Sekeres stated. Notably, the development of MDS consists of multiple genetic steps, and patients typically acquire 3 or 4 driver mutations before their MDS diagnosis, he explained. However, researchers are still unsure whether smoking could contribute to the development of these early-disease driver mutations, according to Sekeres. If so, health care providers may decide to counsel patients about the benefits of smoking cessation before the potential development of a malignancy such as MDS, he concluded.