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서울대학교
J. Thorac. Oncol., Jul 06 2026, S1556-0864(26)00522-8 | https://doi.org/10.1016/j.jtho.2026.104069
Germline Mutations as Risk Factors for Lung Cancer: A Systematic Review and Meta-analysis
Ji Young Lee MD, PhD 1∗, Sheehyun Kim MD 2∗, Kwon Joong Na MD 3,4,5, Jin Mo Goo MD, PhD 1,4,6, Soon Ho Yoon MD, PhD 7
1Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
2Department of Genomic Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
3Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
4Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
5Portrai, Inc, Seoul, 04798, Republic of Korea
6Institute of Radiation Medicine, Seoul National University Medical Research Center, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
7Department of Radiology, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA
∗Drs. Lee and Kim equally contributed to this work.
Address correspondence to: Soon Ho Yoon, MD, PhD.
1Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
2Department of Genomic Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
3Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
4Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
5Portrai, Inc, Seoul, 04798, Republic of Korea
6Institute of Radiation Medicine, Seoul National University Medical Research Center, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
7Department of Radiology, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA
∗Drs. Lee and Kim equally contributed to this work.
Address correspondence to: Soon Ho Yoon, MD, PhD.
Abstract
Introduction
Inherited predispositions to lung cancer are increasingly recognized, but the prevalence and distribution of pathogenic germline variants (PGVs) remain incompletely characterized.
Methods
We performed a systematic literature review of studies reporting the prevalence of pathogenic or likely pathogenic (P/LP) germline variants in lung cancer patients. Random-effects models pooled overall prevalence estimates and gene-specific frequencies for commonly reported genes (EGFR, BRCA1, BRCA2, ATM, CHEK2, TP53). Subgroup analyses were performed according to cohort type and ancestry. Univariable meta-regression evaluated associations of mean age and sequencing panel size with P/LP prevalence. Case reports and series were qualitatively summarized.
Results
Twenty-eight studies were included in the meta-analysis. The pooled prevalence of P/LP PGVs was 7.9% (95% CI, 3.8–15.9%) with high heterogeneity (I2=98.8%). Gene-specific prevalence rates were: BRCA2, 0.96%; ATM, 0.67%; TP53, 0.57%; CHEK2, 0.49%; BRCA1, 0.48%; and EGFR, 0.17%. The high-risk enriched cohort had a higher prevalence of P/LP PGVs, while variants in DNA damage repair genes were more frequent in non-Asian populations than in East Asians (p<0.05). Higher PGV prevalence was associated with lower study-level mean age (per-year OR 0.91 for increasing age; p=0.024) and larger sequencing panels (per log increase in tested genes OR, 1.72; p = 0.013). Case reports described over 15 rare PGVs, most frequently involving EGFR, particularly EGFR T790M.
Conclusions
Approximately 8% of lung cancer patients harbor P/LP germline variants, with the highest frequencies in DNA damage repair genes. Study-level younger age and non-Asian ancestry are associated with higher prevalence, informing genetic evaluation with established risk factors.
Inherited predispositions to lung cancer are increasingly recognized, but the prevalence and distribution of pathogenic germline variants (PGVs) remain incompletely characterized.
Methods
We performed a systematic literature review of studies reporting the prevalence of pathogenic or likely pathogenic (P/LP) germline variants in lung cancer patients. Random-effects models pooled overall prevalence estimates and gene-specific frequencies for commonly reported genes (EGFR, BRCA1, BRCA2, ATM, CHEK2, TP53). Subgroup analyses were performed according to cohort type and ancestry. Univariable meta-regression evaluated associations of mean age and sequencing panel size with P/LP prevalence. Case reports and series were qualitatively summarized.
Results
Twenty-eight studies were included in the meta-analysis. The pooled prevalence of P/LP PGVs was 7.9% (95% CI, 3.8–15.9%) with high heterogeneity (I2=98.8%). Gene-specific prevalence rates were: BRCA2, 0.96%; ATM, 0.67%; TP53, 0.57%; CHEK2, 0.49%; BRCA1, 0.48%; and EGFR, 0.17%. The high-risk enriched cohort had a higher prevalence of P/LP PGVs, while variants in DNA damage repair genes were more frequent in non-Asian populations than in East Asians (p<0.05). Higher PGV prevalence was associated with lower study-level mean age (per-year OR 0.91 for increasing age; p=0.024) and larger sequencing panels (per log increase in tested genes OR, 1.72; p = 0.013). Case reports described over 15 rare PGVs, most frequently involving EGFR, particularly EGFR T790M.
Conclusions
Approximately 8% of lung cancer patients harbor P/LP germline variants, with the highest frequencies in DNA damage repair genes. Study-level younger age and non-Asian ancestry are associated with higher prevalence, informing genetic evaluation with established risk factors.
논문정보
- Research article
- 2026년 07월 (BRIC 등록일 2026-07-09)
- 국내+국외 연구진
- 의약학 > 응용의학
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