ArticleCancer2021
Germline mutations and age at onset of lung adenocarcinoma.
Article in Cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 3 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 3 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Limitations of nomogram models in predicting survival outcomes for glioma patients.Frontiers in immunology · 2025Pooled it
- A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US.Frontiers in genetics · 2023Pooled it
- Cancer Predisposition Genes in Adolescents and Young Adults (AYAs): a Review Paper from the Italian AYA Working Group.Current oncology reports · 2022Pooled it
- NovelTranslational lung cancer research · 2025Article
- Age-specific familial risks in cancer as clues to germline genetic and environmental causes: focus on colorectal, endometrial, prostate, kidney, breast and lung cancers.Hereditary cancer in clinical practice · 2025Review
- Association of Germline Pathogenic Variants inJCO precision oncology · 2025Article
- A profile of lung cancer in the young population with a highlight on the Indian perspective.Frontiers in oncology · 2025Review
- Integrative Analysis of Germline Rare Variants in Clear and Non-clear Cell Renal Cell Carcinoma.European urology open science · 2024Article
- New insights into the biology and development of lung cancer in never smokers-implications for early detection and treatment.Journal of translational medicine · 2023Review
- Hereditary cancer syndromes.World journal of clinical oncology · 2023Review
- Whole Exome Sequencing reveals clinically important pathogenic mutations in DNA repair genes across lung cancer patients.American journal of cancer research · 2023Article
- Germline mutations in high penetrance genes are associated with worse clinical outcomes in patients with non-small cell lung cancer.JTCVS open · 2022Article
- Clonal Hematopoiesis and Mosaicism Revealed by a Multi-Tissue Analysis of Constitutional TP53 Status.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Article
- Small Cell Lung Cancer Transformation following Treatment in EGFR-Mutated Non-Small Cell Lung Cancer.Journal of clinical medicine · 2022Article
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundTo identify additional at-risk groups for lung cancer screening, which targets persons with a long history of smoking and thereby misses younger or nonsmoking cases, the authors evaluated germline pathogenic variants (PVs) in patients with lung adenocarcinoma for an association with an accelerated onset.
methodsThe authors assembled a retrospective cohort (1999-2018) of oncogenetic clinic patients with lung adenocarcinoma. Eligibility required a family history of cancer, data on smoking, and a germline biospecimen to screen via a multigene panel. Germline PVs (TP53/EGFR, BRCA2, other Fanconi anemia [FA] pathway genes, and non-FA DNA repair genes) were interrogated for associations with the age at diagnosis via an accelerated failure time model.
resultsSubjects (n = 187; age, 28-89 years; female, 72.7%; Hispanic, 11.8%) included smokers (minimum of 5 pack-years; n = 65) and nonsmokers (lighter ever smokers [n = 18] and never smokers [n = 104]). Overall, 26.7% of the subjects carried 1 to 2 germline PVs: TP53 (n = 5), EGFR (n = 2), BRCA2 (n = 6), another FA gene (n = 11), or another DNA repair gene (n = 28). After adjustment for smoking, sex, and ethnicity, the diagnosis of lung adenocarcinoma was accelerated 12.2 years (95% confidence interval [CI], 2.5-20.6 years) by BRCA2 PVs, 9.0 years (95% CI, 0.5-16.5 years) by TP53/EGFR PVs, and 6.1 years (95% CI, -1.0 to 12.6 years) by PVs in other FA genes. PVs in other DNA repair genes showed no association. Germline associations did not vary by smoking.
conclusionsAmong lung adenocarcinoma cases, germline PVs (TP53, EGFR, BRCA2, and possibly other FA genes) may be associated with an earlier onset. With further study, the criteria for lung cancer screening may need to include carriers of high-risk PVs, and findings could influence precision therapy and reduce lung cancer mortality by earlier stage diagnosis.
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