Smoking Leads To “Nonsense Mutations” That Weaken Anti-Cancer Defenses, Study Shows

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Researchers at the Ontario Institute for Cancer Research (OICR) have identified how tobacco smoking leads to cancer and hinders its treatment by weakening the body’s anti-cancer defenses.

Smoking associated with “stop-gain mutations”

The recent study in Science Advances associates tobacco smoking with “stop-gain mutations” in DNA, instructing the body to halt protein production prematurely. These mutations are notably common in tumor-suppressor genes, which typically inhibit the growth of abnormal cells.

University of Toronto Ph.D. student and study leader Nina Adler said that there was a link between smoking and alterations in DNA that hinder the creation of tumor suppressors. These changes result in abnormal cell growth without proper defense mechanisms, increasing the risk of cancer.

Researchers utilized advanced computational tools to examine DNA from over 12,000 tumor samples spanning 18 cancer types. Their analysis revealed a significant connection between stop-gain mutations in lung cancer and the characteristic DNA changes caused by smoking. Furthermore, their study demonstrated that the extent of smoking correlated with the frequency of these detrimental mutations, potentially increasing the complexity and treatment challenges of cancer.

Associate Professor at the University of Toronto and OICR Investigator, Dr. Jüri Reimand, Tobacco harms DNA and cell function, deactivating critical proteins with significant long-term health consequences.

‘Nonsense’ mutations linked to APOBEC enzymes

The study explores various factors and processes that lead to stop-gain mutations, also known as ‘nonsense’ mutations. These mutations are linked to enzymes like APOBEC, associated with breast cancer and other cancers. Unhealthy diet and alcohol may also harm DNA, but more research is required for a complete understanding. Additionally, the study underscores the significance of its findings in unraveling the role of smoking in cancer, a major global cause.

Adler explained that while it is common knowledge that smoking is linked to cancer, comprehending the molecular mechanisms underlying this connection is a crucial element in gaining insight into how our lifestyle choices impact our susceptibility to cancer.

Dr. Laszlo Radvanyi, the President and Scientific Director of OICR, emphasizes that these recent findings serve to underscore the significant health risks associated with tobacco use.

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