ArticleNPJ precision oncology2021
Rare deleterious germline variants and risk of lung cancer.
Registry-linked trialOpen access · goldAbstract read
In one paragraph
Article in NPJ precision oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02295085 (Fernald Community Cohort - 18 Year Observational Study with Bio Banked Blood and Urine Samples), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Fernald Community Cohort - 18 Year Observational Study with Bio Banked Blood and Urine Samples
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.Nature genetics · 2022Pooled it
- Germline determinants of risk and molecular subtype in young-onset lung cancer.medRxiv : the preprint server for health sciences · 2026Article
- High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology of Lung Cancer Consortium.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Inherited genetic risk factors in young-onset lung cancer.medRxiv : the preprint server for health sciences · 2026Article
- Exome-Wide Association Analysis Identifies Rare Germline Susceptibility Variants in Early-Onset Breast Cancer Among Saudi Women.International journal of molecular sciences · 2026Article
- Expression of PD-L1 in pleural effusion of advanced lung adenocarcinoma and its relationship with DNA ploidy.Pakistan journal of medical sciences · 2025Article
- Non-coding genetic elements of lung cancer identified using whole genome sequencing in 13,722 Chinese.Nature communications · 2025Article
- Genetic Ancestry and Lung Cancer in Latin American Patients: A Crucial Step for Understanding a Diverse Population.Clinical lung cancer · 2025Review
- Investigating the influence of germlineHaematologica · 2025Article
- Germline Whole-Exome Sequencing in Non-Smoker Lung Cancer Patients Reveals Pathogenic Variants in Lung Cancer Driver Genes.Genes, chromosomes & cancer · 2025Article
- Article
- Whole Exome-Wide Association Identifies Rare Variants inCancers · 2024Article
- Single nucleotide variants in lung cancer.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- Transcriptome signatures of host tissue infected with African swine fever virus reveal differential expression of associated oncogenes.Archives of virology · 2024Review
- Scaled Process Priors for Bayesian Nonparametric Estimation of the Unseen Genetic Variation.Journal of the American Statistical Association · 2024Article
- Differences in set-based tests for sparse alternatives when testing sets of outcomes compared to sets of explanatory factors in genetic association studies.Biostatistics (Oxford, England) · 2023Article
- Pathogenic germline variants in BRCA1 and TP53 increase lung cancer risk in Chinese.Cancer medicine · 2023Article
- Large-scale whole exome sequencing studies identify two genes,CTSL and APOE, associated with lung cancer.PLoS genetics · 2023Article
- A Large-Scale Exome-Wide Association Study Identifies Novel Germline Mutations in Lung Cancer.American journal of respiratory and critical care medicine · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
47 authors at 20 institutions in 8 countries.
Yanhong Liu *Dan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Jun Xia *Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7331-0673
James McKayInternational Agency for Research on Cancer, Lyon, France.
Spiridon TsavachidisDan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Xiangjun XiaoInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
Margaret R SpitzDan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Chao ChengDan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-5002-3417
Jinyoung ByunDan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Wei HongInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
Yafang LiDan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Dakai ZhuInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
Zhuoyi SongInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
Susan M RosenbergDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Michael E ScheurerDan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Farrah KheradmandDan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5343-103X
Claudio W PikielnyDepartment of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA.
Christine M LuskKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Ann G SchwartzKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Ignacio I WistubaDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael H ChoChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4907-1657
Edwin K SilvermanChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Joan Bailey-WilsonNational Human Genome Research Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9153-2920
Susan M PinneyUniversity of Cincinnati College of Medicine, Cincinnati, OH, USA.
Marshall AndersonUniversity of Cincinnati College of Medicine, Cincinnati, OH, USA.
Elena KupertUniversity of Cincinnati College of Medicine, Cincinnati, OH, USA.
Colette GabaThe University of Toledo College of Medicine, Toledo, OH, USA.
Diptasri MandalLouisiana State University Health Sciences Center, New Orleans, LA, USA.
Ming YouMedical College of Wisconsin, Milwaukee, WI, USA.
Mariza de AndradeMayo Clinic College of Medicine, Rochester, MN, USA.
Ping YangMayo Clinic College of Medicine, Scottsdale, AZ, USA.
Triantafillos LiloglouRoy Castle Lung Cancer Research Programme, The University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Liverpool, UK.
Michael P A DaviesRoy Castle Lung Cancer Research Programme, The University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Liverpool, UK.ORCID http://orcid.org/0000-0002-7609-4977
Jolanta LissowskaM. Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Beata SwiatkowskaNofer Institute of Occupational Medicine, Department of Environmental Epidemiology, Lodz, Poland.
David ZaridzeRussian N.N. Blokhin Cancer Research Centre, Moscow, Russian Federation.
Anush MukeriaRussian N.N. Blokhin Cancer Research Centre, Moscow, Russian Federation.
Vladimir JanoutFaculty of Health Sciences, Palacky University, Olomouc, Czech Republic.
Ivana HolcatovaInstitute of Public Health and Preventive Medicine, Charles University, 2nd Faculty of Medicine, Prague, Czech Republic.
Dana MatesNational Institute of Public Health, Bucharest, Romania.
Jelena StojsicDepartment of Thoracopulmonary Pathology, Service of Pathology, Clinical Center of Serbia, Belgrade, Serbia.ORCID http://orcid.org/0000-0002-9290-0967
Ghislaine SceloInternational Agency for Research on Cancer, Lyon, France.
Paul BrennanInternational Agency for Research on Cancer, Lyon, France.ORCID http://orcid.org/0000-0002-0518-8714
Geoffrey LiuPrincess Margaret Cancer Center, Toronto, ON, Canada.
John K FieldRoy Castle Lung Cancer Research Programme, The University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Liverpool, UK.ORCID http://orcid.org/0000-0003-3951-6365
Rayjean J HungLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-4486-7496
David C ChristianiHarvard University T. H. Chan School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0301-0242
Christopher I AmosDan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. Chris.Amos@bcm.edu.ORCID http://orcid.org/0000-0002-8540-7023
Baylor College of Medicine · USCentre international de recherche sur le cancer · FRUniversity of Cincinnati Medical Center · USUniversity of Liverpool · GBBrigham and Women's Hospital · USRussian Cancer Research Center NN Blokhin · RUWayne State University · USCentar za Promociju Nauke · RSCharles University · CZDartmouth College · USHarvard University · USLouisiana State University Health Sciences Center New Orleans · USLunenfeld-Tanenbaum Research Institute · CAMayo Clinic · USMayo Clinic in Arizona · USMedical College of Wisconsin · USMichael E. DeBakey VA Medical Center · USNational Human Genome Research Institute · USNofer Institute of Occupational Medicine · PLPalacký University Olomouc · CZ
Funding
Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3MTumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Suzanne AW Fuqua · 2007 to 2026
$73.9MTumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI PAUL M STEMMER · 1985 to 2026
$68.4MGenetic Epidemiology of COPDU01HL089897 · NHLBI · NATIONAL JEWISH HEALTH · PI CRAPO, JAMES D · 2007 to 2021
$56.9MREPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY RESEARCHP30ES006096 · NIEHS · UNIVERSITY OF CINCINNATI · PI PINNEY, SUSAN MENGEL · 1992 to 2022
$35.4MTranslating Molecular and Clinical Data to Population Lung Cancer Risk AssessmentU19CA203654 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Rayjean J. Hung · 2017 to 2026
$23.7MGenetic Epidemiology of COPDU01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2007 to 2021
$20.7MTranslational Research Support CoreP30ES030285 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI Cheryl L. Walker · 2019 to 2026
$14.7MThe Boston Lung Cancer Survival CohortU01CA209414 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI David C Christiani · 2017 to 2026
$12.2MGenetic Epidemiology of CancerZIAHG200331 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BAILEY-WILSON, JOAN ELLEN · 2009 to 2022
$11.7MGENETIC EPIDEMIOLOGY OF LUNG CANCERU01CA076293 · NCI · UNIVERSITY OF CINCINNATI · PI ANDERSON, MARSHALL W · 1999 to 2009
$11.5MTranslational studies of Hsp90 inhibitors in NSCLCP50CA090578 · NCI · DANA-FARBER CANCER INST · PI MEYERSON, MATTHEW L. · 2008 to 2012
$11.4MCCR NIH HHS HHSN261201300011CNCI NIH HHS DP1 CA174424NCI NIH HHS K07 CA181480NCI NIH HHS P30 CA022453NCI NIH HHS P30 CA023108NCI NIH HHS P30 CA125123NCI NIH HHS P50 CA090578NCI NIH HHS R01 CA060691NCI NIH HHS R01 CA074386NCI NIH HHS R01 CA080127NCI NIH HHS R01 CA084354NCI NIH HHS R01 CA087895NCI NIH HHS R01 CA092824NCI NIH HHS R01 CA127219NCI NIH HHS R01 CA134433NCI NIH HHS R01 CA134682NCI NIH HHS R01 CA141769NCI NIH HHS R01 CA250905NCI NIH HHS R03 CA077118NCI NIH HHS U01 CA076293NCI NIH HHS U01 CA209414NCI NIH HHS U01 CA243483NCI NIH HHS U19 CA148127NCI NIH HHS U19 CA203654NCRR NIH HHS S10 RR024574NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS N01 HG065404NHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201200007CNHLBI NIH HHS R01 HL082487NHLBI NIH HHS R01 HL110883NHLBI NIH HHS R01 HL113264NHLBI NIH HHS U01 HL089856NHLBI NIH HHS U01 HL089897NIA NIH HHS DP1 AG072751NIEHS NIH HHS P30 ES006096NIEHS NIH HHS P30 ES030285NIGMS NIH HHS P20 GM103534NIGMS NIH HHS R35 GM122598World Health Organization 001
Abstract
Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls. During discovery, we identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar. Of the five validated candidates, we discovered two pathogenic variants in known LC susceptibility loci, ATM p.V2716A (Odds Ratio [OR] 19.55, 95%CI 5.04-75.6) and MPZL2 p.I24M frameshift deletion (OR 3.88, 95%CI 1.71-8.8); and three in novel LC susceptibility genes, POMC c.*28delT at 3' UTR (OR 4.33, 95%CI 2.03-9.24), STAU2 p.N364M frameshift deletion (OR 4.48, 95%CI 1.73-11.55), and MLNR p.Q334V frameshift deletion (OR 2.69, 95%CI 1.33-5.43). The potential cancer-promoting role of selected candidate genes and variants was further supported by endogenous DNA damage assays. Our analyses led to the identification of new rare deleterious variants with LC susceptibility. However, in-depth mechanistic studies are still needed to evaluate the pathogenic effects of these specific alleles.
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Read underepoch 390
Registered trials
NCT02295085ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.