Lung Cancer Risk: The Role of Family History and Germline Genetic Alterations

Cheryl Czerlanis, MD, a professor of medicine and thoracic oncologist at the University of Wisconsin Carbone Cancer Center, joined Lung Cancers Today to discuss her presentation on the role of family history and germline mutations in lung cancer risk at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

The presentation was part of the session that Dr. Czerlanis chaired, which was titled “Broadening the Net: Overcoming Challenges and Embracing Novel Technologies in Lung Cancer Screening on a Global Scale.”

Dr. Czerlanis explained why it was critical to offer this educational presentation on the role of family history and germline mutations in lung cancer risk.

“We know that individuals with family members affected by lung cancer have an increased risk of developing the disease themselves,” Dr. Czerlanis said. “The eligibility criteria associated with our current screening guidelines focus on age and smoking history and may miss more than 50% of lung cancers. This is especially important in certain parts of the world, such as East Asia, where many lung cancers are diagnosed in never smokers, especially in women.”

As the field’s understanding of the inherited risk of lung cancer continues to evolve, there are multiple opportunities to start identifying and addressing this risk.

“Identifying germline pathogenic variants that portend risk for developing lung cancer may allow for improved selection of lung cancer screening in at-risk family members,” Dr. Czerlanis explained.

However, in the United States, the guidelines for lung cancer screening “currently do not take into account family history or a genetic predisposition to lung cancer,” she said. However, in other regions of the world, strategies have been evaluated and implemented.

“In Asia, given the high rates of lung cancers in never-smokers, other risk factors such as family history have been investigated,” Dr. Czerlanis said. “Some Asian countries have adapted lung cancer screening guidelines that incorporate family history. Taiwan is one such example, where lung cancer screening guidelines include individuals with a history of heavy smoking as well as individuals with a family history of lung cancer.”

However, she said that at this time in the United States, “more information is needed to determine the potential benefits and harms of screening these additional populations.”

“We know that in high-risk individuals with a history of smoking, the uptake of lung cancer screening is still low,” Dr. Czerlanis said. “Expanding lung cancer screening to other populations will really take a thoughtful approach and more investigation to determine what is the magnitude of benefits in terms of the number needed to screen and whether this level of expanded screening makes sense at the population level.”

She explained that there is currently ongoing work in the United States to study risk factors for lung cancer in people who have never smoked, such as the FANS study being conducted at the University of California, San Francisco, which includes Asian women who do not have a history of smoking.

“My hope is that gaining more insight into the root causes of lung cancer in nonsmokers will lay the groundwork for whom and how to screen individuals who may be at risk for lung cancer due to factors other than age and smoking on a larger scale,” Dr. Czerlanis said. “My passion for lung cancer screening fuels my hope that there will be equitable access to screening for more people at risk and that we will continue to explore how to improve this tool and decrease more deaths from lung cancer.”