ASCO Expert Perspective
“Although most lung cancer can be attributed to smoking and other environmental causes, an inherited predisposition to developing lung cancer impacts thousands of patients. These pathogenic germline variants not only can contribute to developing lung cancer at earlier age or in the absence of other risk factors, but also increase the risk of developing other cancers, such as ovarian, pancreatic, and prostate cancers, and may impact therapeutic options. Knowledge of an inherited variant can also alert extended family members to their cancer risk.”
– Jyoti D. Patel, MD, FASCO, ASCO Expert in lung cancer
ALEXANDRIA, Va. --Testing for pathogenic germline variants (PGVs) – genetic changes present from the time of conception, those that have been inherited – can help identify patients at risk for hereditary cancers. The role of PGVs in lung cancer has been underrecognized, largely due to the fact that it is mostly assumed to be caused by environmental factors such as cigarette smoking. A new study of patients with lung cancer, however, found that nearly 15% had PGVs, which means they and their family members are at an increased risk for other types of cancers. The results of the study will be presented during the ASCO Plenary Series session taking place August 16, 2022, at 3:00 PM (ET).
Germline changes in cells differ from somatic (or acquired) changes, which occur throughout the course of a person’s life because of factors such as tobacco use, sun exposure, and aging. While somatic changes are the most common cause of cancer, knowledge of germline changes can be beneficial for the prevention and early detection of cancer and to identify the best course of treatment.
In the study, researchers performed germline DNA sequencing on 7,788 patients with lung cancer and found a total of 1,503 PGVs in 81 known cancer-risk genes were identified in 1,161 (14.9%) patients. Of these patients, 1,104 (95.1%) had a PGV that could potentially be treated either with therapy with approved drugs or clinical trials, or with prevention and early detection. In addition, 712 (61.3%) specifically had a PGV in the DDR/HRR gene, making them potentially eligible for treatment with targeted therapies being used in other cancers that have the same variant, such as breast, pancreatic, prostate, and ovarian cancers.
According to the researchers, there are a number of implications of these findings:
- The diagnosis of a hereditary cancer syndrome means that the patient has an increased risk for other types of cancer besides lung cancer.
- Blood relatives of patients with PGVs indicating hereditary cancer are at risk for having the same PGV. Identifying family members with these PGVs will allow them to mitigate their risk through increased surveillance and prevention.
“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,” said Renato Martins, MD, MPH, chair of hematology, oncology, and palliative care at the VCU Massey Cancer Center and the presenting author of the study. “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.”
The authors note potential limitations of this study may include selection bias in referrals for genetic testing and variation in which genes were selected for testing.
Abstract and presentation will be available here on August 16, 2022, at 3:00 PM (ET).
View the author disclosures: https://coi.asco.org/Report/ViewAbstractCOI?id=388570
View the disclosures for Dr. Patel: https://coi.asco.org/share/U7C-NPST/Jyoti
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