Cancer-Related Pathogenic Germline Variants Identified in 7.9% of Lung Cancer Patients
- Numerous variants found in DNA damage repair genes, such as BRCA2, ATM, TP53, CHEK2, and BRCA1
- Prevalence is high at 32.3% in high-risk groups, including those with a family history of lung cancer or early-onset lung cancer
[Figure 1] Overall prevalence of pathogenic or likely pathogenic (P/LP) germline variants in lung cancer patients, and prevalence by major gene
A Korean research team has published the results of a meta-analysis identifying genetic predispositions potentially linked to cancer development in 7.9% of lung cancer patients. Notably, the prevalence reached approximately 32% in high-risk groups selected based on a family history of lung cancer, early-onset lung cancer, or multiple primary lung cancers.
Lung cancer is a leading cause of cancer-related deaths worldwide, with smoking recognized as a primary risk factor. However, interest in genetic predispositions is growing because some cases, such as lung cancer in never-smokers or younger individuals, are difficult to explain by environmental factors alone. Previous studies had limitations in comprehensively assessing the distribution of “pathogenic germline variants,” the genetic predispositions in question, owing to differences in study populations and the scope of testing.
A joint research team comprising Professors Lee, Ji-Young (Department of Radiology), Kim, Shee-Hyun (Department of Genomic Medicine), Na, Kwon-Joong (Department of Thoracic and Cardiovascular Surgery), and Goo, Jin-Mo (Department of Radiology) of Seoul National University Hospital, along with Professor Yoon, Soon-Ho (Department of Radiology) of National Jewish Health, analyzed 28 studies on lung cancer to determine the overall and gene-specific prevalence of pathogenic or likely pathogenic (P/LP) germline variants and to identify associated factors.
The study found that the overall prevalence of these variants among lung cancer patients was 7.9%, with high rates observed mainly in DNA damage repair genes. By gene, prevalence was highest for BRCA2 (0.96%), followed by ATM (0.67%), TP53 (0.57%), CHEK2 (0.49%), and BRCA1 (0.48%).
[Figure 2] Comparison of prevalence between the unselected patient group (4.7%) and the high-risk group (32.3%)
Differences in prevalence according to patients’ clinical characteristics were also observed. The prevalence in the high-risk group, selected based on criteria such as family history, early-onset lung cancer, and multiple primary lung cancers, was 32.3%, significantly higher than the 4.7% in the unselected patient group.
While the difference in overall prevalence by ancestry was not significant, variants in key DNA damage repair genes were more common in non-Asian or mixed populations than in East Asian populations.
Additionally, prevalence of pathogenic variants tended to be higher in patient groups with a lower mean age and in studies that tested a larger number of genes.
Professor Lee, Ji-Young (Department of Radiology) said, “This study showed a high prevalence of pathogenic germline variants in patients with high-risk characteristics, such as a family history and early-onset lung cancer.” She added, “These findings may serve as basic data for considering the role of risk-adapted genetic evaluation in high-risk patients, and suggest the potential to help with cancer prevention and early diagnosis for patients and their families.”
Professor Kim, Shee-Hyun (Department of Genomic Medicine) said, “Genetic predispositions such as BRCA1/2 variants are well known in breast and ovarian cancers, but the distribution and characteristics of genetic factors in lung cancer have been relatively less well known.” He added, “This study is significant in that it systematically presents the genetic predispositions of lung cancer by synthesizing existing studies.”
The study was published online in the international journal Journal of Thoracic Oncology (Impact Factor: 23.3).
[Photo from left] Professor Lee, Ji-Young (Department of Radiology), Professor Kim, Shee-Hyun (Department of Genomic Medicine), Professor Na, Kwon-Joong (Department of Thoracic and Cardiovascular Surgery), Professor Goo, Jin-Mo (Department of Radiology) of Seoul National University Hospital, Professor Yoon, Soon-Ho (Department of Radiology) of National Jewish Health