15% of People With Lung Cancer Have an Inherited Mutation for Cancer Risk: The ASCO Plenary Series

ASCO ® Plenary Series
August 15, 2022
Brielle Gregory Collins, ASCO staff

The pace of progress in cancer research keeps getting faster and faster. However, the results of this research can take time to reach the medical community. The ASCO Plenary Series is a program developed by the American Society of Clinical Oncology (ASCO) to help speed the delivery of high-impact cancer research. In this series, cancer care providers gather online to learn about new, carefully selected research and discuss the study results with their colleagues.

The August 2022 session in the ASCO Plenary Series features a study on identifying inherited mutations in people diagnosed with lung cancer.

  • About 15% of people with lung cancer have inherited genetic mutations known to increase cancer risk

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About 15% of people with lung cancer have inherited genetic mutations known to increase cancer risk

Who does this study affect? People diagnosed with lung cancer and their families.

What did this study find? A study of data from germline testing results found that about 15% of people with lung cancer have pathogenic germline variants (PGVs) in genes that are known to increase cancer risk. Of the participants who had a PGV, more than 60% had a PGV that could possibly be targeted with treatment. PGVs are mutations, or changes, in a person’s inherited genes that increase their risk for cancer.

Germline testing is a type of genetic testing that looks to identify inherited mutations in a person’s DNA, called “germline mutations.” Most research on why lung cancer develops has focused on smoking, which can cause a different type of mutation called an “acquired” or “somatic” mutation that can eventually lead to lung and other cancers. Germline testing during cancer can be helpful for several reasons:

  1. If a germline mutation is identified, doctors can recommend treatments to directly target the specific gene causing the cancer to grow or spread, if there is a known treatment available. This type of treatment is called “targeted therapy.”

  2. It can inform people with cancer of their increased risk for developing other cancers associated with the same germline mutation, so they can receive screening and monitoring, if necessary.

  3. It can alert the family members of a person with a germline mutation that they may also have inherited the mutation and have an increased cancer risk. This can help guide their individual genetic testing and cancer screening plans.

While there are recommendations for germline testing in some other types of cancer, such as colorectal cancer, there are no official recommendations for germline testing in people with lung cancer.

It is estimated that 236,740 people in the United States will be diagnosed with lung cancer this year, and it is the leading cause of cancer death in the United States and worldwide.

This study analyzed the data from 7,788 people with primary lung cancer who received germline genetic testing between 2014 and 2022. Primary lung cancer is cancer that starts in the lungs. Of the participants, the majority were female (71.1% of participants), White (64.5% of participants), and had a history of more than 1 cancer (71.1% of participants).

The study found that nearly 15% of participants (1,161 people) had PGVs in genes known to increase cancer risk. Overall, a total of 1,503 PGVs were found among 81 different cancer-risk genes in these 1,161 people. There were 229 more participants who had a PGV in a gene associated with “autosomal recessive inheritance,” which means they inherited 1 copy of a mutated gene from both parents.

The most common PGVs were in the BRCA2 (2.8% of participants), CHEK2 (2.1%), ATM (1.9%), TP53 (1.3%), BRCA1 (1.2%), and EGFR (1%) genes. Of the 1,161 people with 1 or more PGVs, 712 (61.3%) had a PGV that could possibly be treated with an existing targeted therapy in a clinical trial. Finally, among those with a PGV, about 95% had a PGV that could possibly help guide their individual treatment and screening recommendations.

What does this mean for patients? This study expands the scientific knowledge about what causes lung cancer and finds that people may benefit from germline genetic testing after a lung cancer diagnosis. Testing results can potentially help guide cancer treatment decisions, as well as provide helpful information about their and their family’s future health.

Read this abstract and authors’ disclosures on ASCO.org.

“The substantial frequency of PGVs in lung cancer patients, regardless of family history or personal history of other cancers, is similar to the frequency seen in all of the other common solid tumors for which testing is now recommended. For the reasons testing is recommended for these other cancers, lung cancer patients should not be deprived of the opportunity to learn of their risks for other cancers, to help family members determine their risks, and to benefit from the management and the potential therapeutic implications of finding PGVs in DNA repair pathways.”

—   Renato Martins, MD, MPH
VCU Massey Cancer Center
Richmond, Virginia


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