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Published on: September 20, 2016
Association Between Rare Germline Variants in Cancer Susceptibility Genes and Lung Cancer Risk
Sierra R Broad1, Jun Wei2, Keri Denson1
1Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Illinois, USA.
The Annals of Thoracic Surgery
|July 31, 2026
Summary
Researchers identified eight hereditary cancer genes linked to lung cancer risk. Rare germline variants in these genes, including novel ones like RB1 and MET, are associated with increased lung cancer risk and earlier diagnosis.
Area of Science:
- Genetics
- Oncology
- Cancer Genomics
Background:
- Establishing germline susceptibility genes for lung cancer remains challenging.
- This study investigates the role of known hereditary cancer genes in lung cancer risk.
Purpose of the Study:
- To evaluate the association between germline variants in 123 ClinGen-curated hereditary cancer genes and lung cancer risk.
- To identify novel genetic contributors to lung cancer susceptibility.
Main Methods:
- Analysis of rare pathogenic germline variants in European ancestry cohorts (UK Biobank and RUSH/gnomAD).
- Gene-based burden testing (robust SKAT-O) and meta-analysis were employed.
- Evaluation included 2,272 lung cancer (LC) cases and 56,878 controls.
Main Results:
- Suggestive evidence for eight genes associated with increased lung cancer risk (p<0.05) was identified via meta-analysis.
- Three previously reported genes (ATM, BRCA2, TP53) and five novel genes (RB1, MET, CYLD, PDGFRA, CTNNA1) were implicated.
- Aggregated rare pathogenic variants in these eight genes correlated with lung cancer risk and earlier diagnosis, independent of smoking history.
Conclusions:
- Suggestive evidence supports associations between rare germline variants in eight hereditary cancer genes and lung cancer.
- These findings contribute to understanding the genetic architecture of lung cancer.
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