New DNA research could lead to personalized cancer prevention for smokers

Using advanced genomic tools, the team discovered that DNA’s environment plays a crucial role in determining how much damage occurs and how well cells can repair it.

By Pesach Benson, TPS

New research about how smoking damages DNA could open new possibilities for targeted cancer prevention.

Israeli and US researchers found that the way DNA is organized and chemically modified influences how cigarette smoke affects it.

In a study recently published in the peer-reviewed journal, Nucleic Acids Research, the scientists found that some areas of DNA are more open and active, making them more vulnerable to damage but also more efficient at repairing themselves. Other regions are less capable of repair, allowing mutations to develop and potentially lead to cancer.

The researchers from The Hebrew University of Jerusalem, led by Prof. Sheera Adar and graduate student Elisheva Heilbrun-Katz — collaborated with Prof. Raluca Gordan from Duke University and the University of Massachusetts — also provides new insights into how smoking-related lung cancer develops.

Globally, tobacco use is a leading cause of cancer-related deaths. In 2019, it was responsible for approximately 2.6 million cancer deaths, accounting for about 25% of all cancer fatalities worldwide, according to the American Cancer Society.

Around 8,000 Israelis die from illnesses caused by active or passive smoking, including various cancers, heart attacks, strokes, and chronic obstructive pulmonary disease, according to figures released by the Israeli Health Ministry in January.

To examine how DNA structure and chemical modifications affect damage from cigarette smoke and the body’s ability to repair it, the researchers focused on benzo[a]pyrene, a harmful chemical found in cigarette smoke.

When processed by the body, it turns into Benzo[a]pyrene diol epoxide (BPDE), a substance that binds to DNA and interferes with its normal function.

Using advanced genomic tools, the team discovered that DNA’s environment plays a crucial role in determining how much damage occurs and how well cells can repair it.

Open and active regions of DNA experience more damage but are also repaired more efficiently. Transcription factors, proteins that regulate gene activity, can either protect DNA from damage or increase its vulnerability.

The study also found that the efficiency of DNA repair is a key factor in whether mutations form, regardless of how much damage initially occurs.

The research suggests that the body’s ability to fix DNA damage is more important than the extent of the damage itself in determining cancer risk.

Understanding that some DNA regions are more vulnerable to smoking-induced mutations could help identify high-risk individuals based on genetic and epigenetic factors.

This could lead to personalized smoking cessation programs or targeted monitoring for early cancer detection.

Moreover, if certain transcription factors influence DNA repair efficiency, drugs could be developed to enhance repair in vulnerable regions, potentially reducing the mutation burden and slowing cancer progression.

The findings could help identify specific genetic or epigenetic markers that indicate a higher risk of lung cancer, allowing for earlier and more precise screening methods.

And in the long-term, modifying DNA repair mechanisms through gene therapy or epigenetic drugs might help protect high-risk individuals from accumulating smoking-related mutations.