New study reveals how smoking alters DNA, raising cancer risk

Scientists from Israel and the United States have uncovered how cigarette smoke damages DNA, shedding light on the mechanisms that lead to smoking-related cancers. Their research, published in Nucleic Acids Research, highlights the role of DNA structure and chemical modifications in determining which regions are most vulnerable to mutations.

The study, led by Prof Sheera Adar and graduate student Elisheva Heilbrun-Katz of The Hebrew University of Jerusalem, in collaboration with Prof Raluca Gordan of Duke University and the University of Massachusetts, offers new insights into how tobacco use drives cancer development.

The findings suggest that some DNA regions, due to their open and active nature, sustain more damage but also have better repair mechanisms. In contrast, less active regions struggle to fix mutations, increasing the risk of cancerous changes.

Tobacco remains one of the world’s most significant cancer risk factors. According to the American Cancer Society, smoking caused around 2.6 million cancer deaths globally in 2019, accounting for roughly 25% of all cancer fatalities. In Israel alone, approximately 8,000 people die annually from smoking-related illnesses, including cancer, heart disease, and chronic respiratory conditions, according to data from the Israeli Health Ministry.

To understand how smoking damages DNA, the researchers focused on benzo[a]pyrene, a toxic chemical in cigarette smoke. Once metabolised, it becomes benzo[a]pyrene diol epoxide (BPDE), a compound that binds to DNA, interfering with its normal function. Using advanced genomic tools, the team found that DNA’s surrounding environment is crucial in determining how much damage occurs and how efficiently cells can repair it.

The study also revealed that transcription factors—proteins that regulate gene activity—can influence DNA repair. Some offer protection, while others increase susceptibility to damage. Notably, the ability of cells to repair DNA damage appears to be more important than the initial level of damage in determining cancer risk.

These findings could pave the way for personalized cancer prevention strategies. Identifying individuals with genetic or epigenetic markers indicating heightened vulnerability to smoking-induced mutations could allow for targeted monitoring and intervention. Additionally, if specific transcription factors impact DNA repair efficiency, drugs might be developed to enhance repair processes, potentially reducing cancer risk.

In the long run, modifying DNA repair pathways through gene therapy or epigenetic treatments could provide new approaches to protecting high-risk individuals from smoking-related cancers.