Did You Know That 1 in 7 Lung Cancers Involves Inherited Mutations?

With more than 2 million new cases each year, lung cancer remains among the most common cancers, alongside breast cancer at the top of the list. Although about 90% of lung cancers are linked to smoking, not every smoker has the same risk. Lung cancer also occurs in people who have never smoked. This shows that its causes are not limited to smoking and other chemical exposures. Recent genetic research suggests that inherited factors may also contribute to lung cancer development. These findings support wider use of genetic testing in lung cancer diagnosis and treatment.

Inherited Mutations Identified in 15% of Lung Cancers

JCO Precisicion Oncology published a study on November 22, 2023, showing that about one in seven lung cancer patients who underwent genetic testing had pathogenic germline variants (PGVs) identified by testing.

This frequency is higher than previously reported, suggesting that germline genetic testing may be appropriate for all patients with lung cancer.

Researchers reviewed data from 7788 lung cancer patients who underwent genetic testing between 2015-2022.

Patients were tested using gene panels examining 159 different genes. Most tests used panels covering 80-84 genes (44.1%) or 42-47 genes (22.4%).

Graph descriptions: Genetic test results among all patients in the cohort. (A) Overall results, showing the proportions with positive, carrier, uncertain and negative results. (B) The most frequently identified pathogenic germline alterations among people with positive results.

Testing identified a pathogenic genetic variant in 14.9% of patients, a total of 1161. No pathogenic variants or variants of uncertain significance were found in 49.3%. Results were uncertain in 32.8%, while 2.9% were classified as carriers of particular genetic variants.

In analyses focusing on specific genes in more than 1000 patients, the researchers found pathogenic variants most commonly in the BRCA2 gene (2.8%), the CHEK2 gene (2.1%) and the ATM gene (1.9%). EGFR variants were also detected in 0.9% of these patients.

Of the 1161 patients with pathogenic variants, 61.3% carried variants in DNA damage repair genes and were therefore potentially eligible for clinical trials. Overall, 1104 patients (95.1%) had findings in genes that could affect clinical management for other cancer types.

Most patients with inherited cancer mutations identified by testing (71.1%) had previously been diagnosed with another cancer. The most common were breast cancer (33.5%), gastrointestinal cancers (23%) and genitourinary cancers (15.4%).

The highest frequencies of pathogenic variants were found in patients with a history of ovarian cancer (20.2%) and other gynecological cancers (18%).

The researchers noted limitations, including different panel sizes and single-gene testing in some patients. These could mean that the actual pathogenic variant rate was higher than reported.

In conclusion, the researchers suggested that routinely checking all patients with lung cancer for pathogenic germline variants (PGVs) in cancer-risk genes could benefit both patients and relatives. Such testing may support personalized treatment and a better understanding of family members' risks.