Beyond Smoking, Lung Cancer Drivers Include Pollution and Genetics

Amid growing recognition of factors that contribute to lung cancer risk, it’s time to think beyond smoking, according to speakers at a session of the 2024 World Conference on Lung Cancer. These factors range from the air in our homes to the makeup of our DNA, and smart policy solutions and mitigation strategies are critical.

First, Joan Schiller, MD, of the Lung Cancer Research Foundation in Virginia, discussed the role of outdoor air pollution in lung cancer. Air pollution from burning fossil fuels is largely discussed in terms of its respiratory and cardiac effects, but it’s also a significant cause of lung cancer and accounts for an estimated 14% of lung cancer–related deaths, Schiller said. The fine particulate matter known as PM_2.5 is especially insidious, as it infiltrates the bronchioles and alveolar cells and causes systemic effects. A 10 mcg/m³ increase in PM_2.5 is associated with an HR for lung cancer of 1.13, and for never-smokers the HR rises to 1.73.¹ Another lung cancer risk factor in the air around us is pollution from wildfires, which are becoming more frequent, more intense, and longer lasting, and their PM_2.5 carries more carbon and thus greater oxidative potential.

Drivers of lung cancer risk beyond smoking range from the air outside and in our homes to the makeup of our DNA | Image Credit: © malp - stock.adobe.com

What can individuals do to combat the effects of outdoor air pollution? Personal actions like reducing use of gas-powered vehicles are great, but those in the room also need to make their voices heard to enact change.

“As health care representatives, we are powerful messengers, and as cancer care professionals, we are very powerful messengers,” Schiller said.

Although genetics are impossible to change, there’s still an advocacy role to be played by the lung cancer community in expanding access to genomic testing, according Andres Cardona, PhD, of Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center in Colombia. Mutation frequency differs across ancestry, and pathogenic germline variants are thought to increase lung cancer risk.

Recent research has shown the prevalence of these variants in cohorts such as Hispanic patients with lung adenocarcinoma, especially male and younger patients,² as well as evidence that carriers of a germline EGFR mutation had longer duration of therapy on osimertinib.³

Ancestry affects not only the molecular epidemiology of the disease, it could also influence pharmacogenomics in patients with oncogenic drivers, and more research is needed. “Although we are all human, we and our diseases are completely different,” he concluded.

Next, Laura Mezquita, MD, PhD, of the Hospital Clinic in Barcelona, Spain, discussed the role of indoor pollutants like radon, a radioactive gas that comes from soil and is associated with 3% to 14% of lung cancer cases. A radon level of 300 Bq/m3, which is the European Union’s reference level, carries the radiation dose equivalent of 274 chest x-rays per year. The specific mechanisms by which it contributes to lung cancer are not fully understood, but given its known DNA-damaging effects, health agencies are striving to spread awareness of the need to measure and mitigate radon in the home.

Other indoor pollutants include secondhand tobacco smoke and vapor, marijuana smoking, and cooking fumes or oil. But Mezquita emphasized that most patients are exposed to not just a single risk factor but several, and we need more research on the shared mechanisms among carcinogens. She and colleagues are now conducting a prospective study on the lung cancer exposome and how the combination of carcinogens and endogenous factors impact quality of life, response to treatment, and survival, in hopes that “with these kinds of multidisciplinary collaborations, we can provide more detailed information and better understanding about the role of these risk factors in lung cancer and to identify the specific groups at risk.”

Finally, Isabelle Soerjomataram, MD, PhD, of the International Agency for Research on Cancer in France, discussed the role of policies to prevent lung cancer by addressing factors other than smoking and how they must be tailored to the prevalent pollution sources and cultural context of each country.

Successful strategies include London’s congestion charge, which saw air pollution decrease after charging a £15 fee to drive in a congested region of the city. The policy was initiated more as a traffic control measure than a health intervention, but Soerjomataram anticipates positive impacts on health and well-being, along with increased revenue for the city that can be reinvested into public transit.

There are many instruments available that policy makers can leverage to reduce air pollution—not just financial as in London’s case but also including regulation, infrastructure, technology, and the built environment. But they must keep a careful eye on any unintended consequences, such as when a law in Indonesia requiring cars to have at least 3 passengers led to drivers hiring children just to sit in a car.

“It’s really important to think of this as multiple [actions] that you can try, and something that’s also sustainable,” Soerjomataram said.

References

1. Coleman NC, Burnett RT, Higbee JD, et al. Cancer mortality risk, fine particulate air pollution, and smoking in a large, representative cohort of US adults. Cancer Causes Control. 2020;31(8):767-776. doi:10.1007/s10552-020-01317-w

2. Arrieta O, Caballé-Pérez E, Hernández-Pedro N, et al. Prevalence of pathogenic or likely pathogenic germline variants in cancer predisposition genes among selected patients with lung adenocarcinoma: the GERMLUNG study. Lung Cancer. 2024;194:107864. doi:10.1016/j.lungcan.2024.107864

3. Oxnard GR, Chen R, Pharr JC, et al. Germline EGFR mutations and familial lung cancer. J Clin Oncol. 2023;41(34):5274-5284. doi:10.1200/JCO.23.01372