Results from a prospective study presented at the American Society of Hematology Annual Meeting & Exposition showed that tobacco smoking was associated with disease progression and with distinct genetic mutations related to myelodysplastic syndromes (MDS), suggesting that smoking potentially contributes to its multistep molecular pathogenesis.
The data from the prospective NHLBI/NCI National MDS Natural History Study included individuals with suspected or recently diagnosed MDS enrolled between June 2016-August 2023. Of 1,898 evaluable patients, 52% (N=979) had a history of cigarette smoking, and 18% still smoked at diagnosis. The mean ± SD cigarettes per day was 15.8 ± 12.5 and the mean ± SD smoking years was 29.8 ± 16.9 years.
After adjustment for sex, age and disease group, smokers had significantly more mutations on average than nonsmokers (2.0 vs 1.4, P=0.04). Moreover, the number of mutations increased significantly with the number of pack-years (PYs) smoked (P =0.006), and those at the 75th and 90th percentiles of PY had 1.8 and 3.5 times the number of mutations, respectively, compared with nonsmokers, indicating a dose-response relationship. Mutation prevalence increased with PY smoked in the gene pathways for chromatin modification and RNA splicing (P<0.03 for both) and for the genes ASXL1 and ETNK1 (P <0.05 in both cases).
The five-year cumulative incidence of disease progression was significantly higher among long-term smokers (20+ years) compared with nonsmokers or those with shorter smoking history (<20 years) (27% vs 18%, P < 0.05).
“Our data suggest that patients with a new MDS diagnosis who are also smokers should be counseled to stop smoking, as it appears to contribute to the acquisition of new genetic mutations that can lead to progression,” the authors wrote.
Reference
Venugopal S, Otterstatter M, DeZern A. Association between smoking intensity, genetic mutations, and disease Progression in myelodysplastic syndromes. Abstract #4597. December 7-10. San Diego, California.
