While it’s widely acknowledged that smoking induces DNA mutations, the specific mechanisms of these mutations have been less clear. Jüri Reimand, Ph.D., a senior author from the Ontario Institute for Cancer Research and associate professor at the University of Toronto, explains, “The new insight from our analysis is that smoking triggers mutations that cause loss of function in genes, essentially deactivating genes and the proteins they produce.”
The research team examined DNA samples from over 12,000 tumor specimens spanning 18 different cancer types. Their analysis unveiled a strong correlation between stop-gain mutations in lung cancer and the distinctive alterations in DNA associated with smoking.
Subsequently, the researchers investigated the impact of smoking. Their findings demonstrated that heavier smoking was linked to a higher incidence of these detrimental mutations, potentially rendering cancer more intricate and challenging to treat.
Not all DNA mutations carry the same weight; certain mutations wield substantial influence. Reimand remarks, “We identified mutations that introduce stop codons in proteins, akin to inserting a period in the middle of a sentence, causing the production of critical proteins to cease. This type of DNA mutation holds particular significance.”
The team also unearthed that these premature stop codons tend to accumulate in tumor suppressor proteins, as cancer seeks to disable or halt their function. Reimand elucidates, “It’s a loss of function mutation that prematurely triggers a stop codon, disrupting the protein’s function earlier than expected. Through our extensive study, we observed a preference for these halts in tumor suppressor proteins via the mutational processes.”
Factors Influencing the Stop-Gain Mutation
The study additionally pinpointed other factors and processes responsible for generating a large number of stop-gain mutations, also known as ‘nonsense’ mutations. Some, such as a set of enzymes called APOBEC, which is closely tied to stop-gain mutations in breast cancer and other cancer types, occur naturally within the body. Other factors like an unhealthy diet and alcohol consumption are also likely to exert similar detrimental effects on DNA. However, Reimand emphasizes that more research is needed to fully grasp the mechanisms involved.
Regarding smoking, the findings from this study provide a crucial piece of the puzzle regarding how smoking contributes to the development of lung cancer. From a preventive perspective, Reimand suggests that individuals might consider reducing their cigarette consumption, given the understanding that cigarettes essentially cause highly harmful mutations leading to gene knockouts in their cells.
Reimand adds, “I believe this study is just the beginning in terms of comprehending how mutational processes and DNA mutations intersect with function, and their origins. As we amass more genomics data and information about our environment, we may gain a deeper understanding of how these mutational processes impact our cells.”
- Genetic differences between smokers and never-smokers with lung cancer- (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932279/)