Cigarette Smoke and Weak DNA Repair: A Double Hit Behind Lung Cancer Risk
Aug 11, 2025
Lung cancer remains the top cancer killer, with smoking as a primary cause, yet not all smokers develop it. Recent research reveals a concerning link: cigarette smoke alongside weakened DNA repair can significantly increase the risk of non-small cell lung cancer. The discussion highlights how reduced levels of the XPC protein play a critical role in cancer susceptibility, underscoring the need for improved early detection and prevention strategies. Discover the complex interplay of these factors shaping lung cancer risk.
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insights INSIGHT
Tobacco Plus Biology Drives NSCLC
NSCLC arises from both environmental and genetic factors, with tobacco smoke as a major driver.\n- Cigarette smoke contains thousands of chemicals that directly damage airway cell DNA, increasing cancer risk.
insights INSIGHT
XPC Protects Against Smoke-Induced Damage
XPC detects specific DNA damage and initiates repair to preserve genomic stability.\n- When DNA repair like XPC fails, damage accumulates and raises risks for NSCLC and COPD.
insights INSIGHT
Healthy Cells More Vulnerable Than Tumors
Healthy bronchial cells become more damaged and die when exposed to smoke, especially with lowered XPC.\n- Lung cancer cells resist smoke and tolerate damage using alternative mechanisms, so XPC reduction affects them less.
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Lung cancer, particularly non-small cell lung cancer (NSCLC), is the deadliest cancer worldwide. Cigarette smoking is one of the main causes, but not every smoker develops the disease. This suggests that other biological factors help determine who develops cancer.
Researchers from the Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indianapolis, and from the Richard L. Roudebush Veterans Affairs Medical Center have now found that cigarette smoke, combined with a weakened DNA repair system, can trigger the early stages of lung cancer, particularly NSCLC. This work, led by first author Nawar Al Nasralla and corresponding author Catherine R. Sears, was recently published in Volume 16 of Oncotarget.
Full blog - https://www.oncotarget.org/2025/08/11/cigarette-smoke-and-weak-dna-repair-a-double-hit-behind-lung-cancer-risk/
Paper DOI - https://doi.org/10.18632/oncotarget.28724
Correspondence to - Catherine R. Sears - crufatto@iu.edu
Video short - https://www.youtube.com/watch?v=UEiCz834a8c
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Keywords - cancer, DNA repair, DNA damage, lung adenocarcinoma, squamous cell carcinoma, Xeroderma Pigmentosum Group C (XPC)
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