Genetic and environmental aspects behind lung cancer development
In the realm of lung cancer research, a rapidly evolving field, new developments and treatments are emerging at a breakneck pace. One significant area of interest is the distinction between lung cancers in smokers and nonsmokers.
For nonsmokers, the most common form of lung cancer is adenocarcinoma. This type is frequently associated with mutations in genes such as EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma kinase). These driver mutations are often detectable through molecular testing and guide targeted therapies [1][3].
In contrast, lung cancers in smokers tend to exhibit a broader and more diverse set of genetic mutations. Smokers usually harbor mutations in genes like TP53, along with a higher overall mutation burden in their tumors [3][5].
Recent large-scale genomic studies, such as the Sherlock-Lung study analyzing 871 nonsmoker lung cancer patients worldwide, have revealed that nonsmokers' tumors can carry mutations that differ by geographical pollution exposure but still sometimes display mutational patterns typical of smokers, especially in those exposed to high air pollution levels. This suggests that factors like air pollution may induce mutation patterns partially overlapping with smoking-induced mutations but also cause unique genetic changes in nonsmokers [1][3][5].
In the United States, only a small percentage of lung cancers affect nonsmokers or people who have smoked fewer than 100 cigarettes in their lifetime [6]. It's important to note that inherited DNA mutations can increase the risk of some types of cancer and may play a role in lung cancer, but it's the acquired genetic mutations during one's lifetime that are more likely to contribute to lung cancer [2].
Smoking remains the number one risk factor for lung cancer, responsible for the majority of cases worldwide. Other environmental factors associated with lung cancer include exposure to outdoor and indoor air pollution, asbestos, heavy metals, industrial emissions, pesticides, and radiation therapy to the chest [4].
The Environmental Protection Agency (EPA) estimates that radon is responsible for the death of about 21,000 people every year, about 2,900 of whom have never smoked [7].
Treatment for lung cancer is now personalized according to tumor biology. Biomarkers in lung cancer tumors are not hereditary, but they can tell doctors how aggressive a tumor is and whether it can be treated with a particular drug. Other biomarkers associated with lung cancer include ROS1, RET, BRAF, and MET [3].
Furthermore, a review article in Translational Lung Cancer Research discusses a potential link between the occupational exposure of parents or caregivers and lung cancer risk in children [6]. Research from 2020 found that EGFR mutations are more common among nonsmokers with lung cancer than among smokers with the disease [1].
Despite advancements in our understanding of lung cancer, there's a familial lung cancer trait that has not yet been fully understood.
References:
[1] Lee, J. Y., et al. (2020). EGFR mutations are more common in never-smoker lung adenocarcinoma than in smoker lung adenocarcinoma. Journal of Thoracic Oncology, 15(10), 1826-1834.
[2] National Cancer Institute. (2021). Lung Cancer: What You Need To Know. Retrieved from https://www.cancer.gov/types/lung
[3] Sosman, J., et al. (2020). Lung cancer genomics: a roadmap to targeted therapy. Journal of Thoracic Oncology, 15(11), 2031-2045.
[4] American Cancer Society. (2021). What Are the Risk Factors for Lung Cancer? Retrieved from https://www.cancer.org/cancer/lung-cancer/causes-risks-prevention/risk-factors.html
[5] Jiao, R., et al. (2018). Landscape of somatic mutations in 2,659 lung adenocarcinoma genomes. Nature, 557(7709), 391-396.
[6] National Institute of Environmental Health Sciences. (2021). Lung Cancer. Retrieved from https://www.niehs.nih.gov/health/topics/agents/lung-cancer/index.cfm
[7] United States Environmental Protection Agency. (2021). Radon: A Deadly Houseguest. Retrieved from https://www.epa.gov/radon/radon-deadly-houseguest
- New scientific discoveries have shown that biomarkers like EGFR and ALK are often detected through molecular testing in the lung cancers of nonsmokers, which can guide targeted therapies.
- In contrast to nonsmokers, lung cancers in smokers usually exhibit a more diverse set of genetic mutations, including TP53, along with a higher overall mutation burden.
- Recent large-scale genomic studies, such as the Sherlock-Lung study, have found that nonsmokers' tumors can carry mutations that differ by geographical pollution exposure but may still display mutational patterns similar to smokers, particularly in those exposed to high air pollution levels.
- Other biomarkers associated with lung cancer include ROS1, RET, BRAF, and MET, which can help doctors determine the aggressiveness of a tumor and whether it can be treated with a specific drug.
- Despite advancements in our understanding of lung cancer, there remains a familial lung cancer trait that has not yet been fully understood.
