NEW YORK, Nov 5, (Agencies): Researchers at the Ontario Institute for Cancer Research (OICR) have unveiled a significant mechanism by which tobacco smoking contributes to cancer development and complicates treatment efforts by undermining the body's natural anti-cancer defenses. Their groundbreaking study, featured in Science Advances, establishes a direct link between tobacco smoking and detrimental alterations in DNA, referred to as 'stop-gain mutations,' which instruct the body to halt the production of specific proteins prematurely.

These stop-gain mutations were found to be particularly prevalent in genes known as 'tumor suppressors,' responsible for producing proteins that typically prevent the growth of abnormal cells. According to Nina Adler, a Ph.D. student at the University of Toronto who spearheaded the study during her postgraduate research at OICR in Dr. Jüri Reimand's lab, "Our study revealed that smoking leads to DNA changes that disrupt the formation of tumor suppressors. In their absence, abnormal cells can proliferate unhindered by the body's defenses, increasing the likelihood of cancer development."

Adler, Reimand, and their team harnessed advanced computational tools to scrutinize DNA from over 12,000 tumor samples spanning 18 different cancer types. Their analysis revealed a robust correlation between stop-gain mutations in lung cancer and the distinctive genetic 'footprint' left by smoking. Subsequently, they explored the influence of smoking intensity and confirmed that heavier smoking resulted in a greater incidence of these detrimental mutations. These mutations ultimately render cancer more intricate and resistant to treatment.

Dr. Jüri Reimand, an OICR Investigator and Associate Professor at the University of Toronto, underscores the profound damage inflicted by tobacco on our DNA and its repercussions for cellular function. He explains, "Tobacco smoking deactivates critical proteins that are the essential building blocks of our cells, significantly impacting our long-term health."

The study also identified other factors and processes that contribute to the emergence of stop-gain mutations, alternatively known as 'nonsense' mutations. Some of these factors, like a class of enzymes named APOBEC, are naturally occurring in the body and are strongly associated with stop-gain mutations in breast cancer and other cancer types. Additionally, unhealthy dietary habits and alcohol consumption are presumed to have similar deleterious effects on DNA, although further research is needed to comprehensively understand these dynamics.

Nina Adler emphasizes the significance of this study in elucidating one of the molecular mechanisms underpinning smoking-related cancer. She states, "While it's common knowledge that smoking is a leading cause of cancer, being able to elucidate one of the intricate pathways at a molecular level is a crucial step in comprehending how our lifestyle choices impact our cancer risk."

Dr. Laszlo Radvanyi, President and Scientific Director of OICR, reinforces the imperative of these new insights, emphasizing that tobacco smoking remains a paramount threat to human health. He concludes, "This study further underscores the extensive harm that smoking inflicts on our bodies and offers compelling evidence that quitting smoking is always the right decision."