So tobacco smoking has already been a very well-known, established risk factor for cancers like lung, breast and oropharynx, etc. and it has shown to cause mutations in these cells as well. So we wanted to look at if the if tobacco smoking causes the same mutations or. And if there is any increased incidence of disease progression in patients with myelodysplastic syndrome as well.
And that's the background for our study. So this is our research project. And we put in a research proposal to the national MDS History steering Committee to see if we can look at this particular data in their data set. So national MDS history study is one of the largest prospective, natural history of MDS study today.
And it has granular level data in terms of tobacco smoking diagnostic category like CCUS, which is precursor for myelodysplastic syndrome. CCUS otherwise if they expanded it would be clonal cytopenia of undetermined significance and Chip and MDS MPN overlap syndromes etc.. So we were very excited to mine this data to see if we could get, any useful information out of this data set.
And yes, we did, and we were able to identify that almost 52% of this study cohort, had people who smoke, and they either they were current smokers or moderate light, medium and heavy smokers. And we defined the smoking intensity as per the standard CDC definitions, which is light, medium and heavy. So light is anybody who smoked for about less than ten years and heavy is who smoked for about more than 30 plus pack years.
So intermediate intensity, medium intensity comes between these two groups. And what we found was most of the, patients that are on the study cohort were older males who were smokers. And they had an increased risk of, cardiovascular disease, which was expected. And within MDS, we did not observe any difference between, risk categories between smokers and non smokers, because this natural MDS history study dataset has, granular level data in the sense of MDS specific genetic mutations.
We wanted to look at how smoking impacts or if it does impact, MDS specific, pathogenic mutations. So we did find that compared to people who do not smoke, people who smoke had enriched mutations in the pathway involving chromatin modification and RNA splicing. And especially when we looked at individual gene levels, we identified that people who smoke, they're enriched with ASXL1, SF 3B1, U2AF1 and ZRSR2
So these are the mutations that are particularly, pathogenic and higher risk for disease progression in myelodysplastic syndrome. And we wanted to look, if there is, any kind of dose response relationship between in between the gradations of that smoking I already mentioned. So what we found was very, very interesting in the sense that people who smoked for a lesser duration of time had maybe twice the risk of, twice the risk of having a higher number of mutations and people who smoked for a longer duration, maybe on the 90th percentile of the pack year, had four times the risk of accumulating more mutations.
So in the myelodysplastic syndrome world, we already know that the number of mutations the patients accumulate, it implies it’ll be disease progression. And it was proven when we looked at the data for five year cumulative incidence of disease progression. So we did find that people who smoke had a higher incidence of disease progression compared to those who don't smoke, as well as when we looked at the gradations.
People who smoke for a lesser time had a lower incidence of disease progression compared to people who smoked for a longer time. And more number of cigarets. So this prompted us to look at the survival data for CCUS, which is a precursor of MDS, and for MDS itself. And we did find a statistically significant difference in survival benefit in patients who smoke and carry the diagnosis of CCUS.
So this is a very important point in the sense that when someone gets diagnosed with a precursor to MDS, this should prompt the physician to talk about tobacco cessation counseling. So the important takeaway from this study is stop smoking, no matter what category of diagnosis you carry, whether this is CCUS, it is the precursor for MDS or myelodysplastic syndrome because no matter what, the more and more cigarets you smoke, the disease is going to progress.
And this particular study provides the strongest evidence that stopping smoking may help with preventing disease progression. So we are always looking at healthy lifestyle preventative setting because these are low cost intervention that that could possibly mean a lot in a patient's trajectory, disease trajectory. So with this data, we could we could tell the patient that okay, the MDS occurrence is not exactly due to the smoking itself, but smoking could accelerate the disease progression.
So regardless of whether it caused the smoking, whether the smoking caused the MDS or MDS happened due to something else, it is prudent to stop smoking at right now so that it may help in preventing disease progression. So I first want to tell them that this is not their fault. Being diagnosed with MDS is not because they smoke or not because like, okay, they did something that made them get this diagnosis.
However, now that we have strong data showing that stopping smoking helps disease helps preventing disease progression, then it is I think this is the time for you to consider stop smoking and let us know how we can help with whatever smoking cessation aids that would be appropriate.
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