Recent research indicates that tobacco smoking is associated with distinct genetic mutations related to myelodysplastic syndromes (MDS). The study found that increased intensity and duration of smoking increased mutations and affected progression. The results were presented at the ASH Annual Meeting.
“MDS occurs due to the acquisition of mutational events over time. Tobacco smoking is a risk factor for MDS and has been associated with distinct genetic mutations in solid cancers,” wrote the authors, led by Sangeetha Venugopal, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami in Florida. “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 researchers used data from the National MDS Natural History Study to investigate associations among smoking intensity and duration and the number and types of genetic mutations in MDS. The study examined bone marrow samples from patients with diagnoses including MDS, MDS/myeloproliferative neoplasm, or clonal cytopenia of undetermined significance (CCUS). Smoking data were self-reported by patients, including smoking intensity (i.e., light, medium, or heavy) and duration.
The analysis included1,898 patients. Of those, 52% (n=979) had a history of smoking history, and 18% were still smoking at diagnosis. The mean number of cigarettes per day was 15.8 (standard deviation [SD]=12.5), and the mean number of years of smoking was 29.8 (SD=16.9).
The proportion of patients with MDS was similar among smokers and non-smokers (41% and 37%, respectively). Smokers and non-smokers had similar numbers of mutations (mean [SD]=2 [2.7] in both groups).
However, in multivariable regression models, after the researchers adjusted for sex, age, and disease group, smokers had significantly more mutations than non-smokers (2 vs 1.4). Smoking appeared to have the greatest effect on chromatin modification, RNA splicing, and the genes ASXL1 and ETNK1.
In addition, the number of mutations increased with pack-years, indicating a dose-response relationship, the researchers said. Patients at the 75th and 90th percentiles of PY had 1.8 and 3.5 times the number of mutations, respectively, compared to non-smokers. Disease progression also was significantly worse among long-term smokers, as compared with non-smokers and patients with a shorter smoking history. Overall survival was significantly lower for smokers only in the CCUS subgroup.
https://ash.confex.com/ash/2024/webprogram/Paper206034.html
Reference
Venugopal S, Otterstatter M, DeZern AE, et al. Association between smoking intensity, genetic mutations, and disease progression in myelodysplastic syndromes. Abstract #4597. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7–10, 2024; San Diego, California.
