SynthesisJournal of the National Cancer Institute2022
Genetic Analysis of Lung Cancer and the Germline Impact on Somatic Mutation Burden.
Synthesis in Journal of the National Cancer Institute, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Genome-wide meta-analysis across East Asian and European populations provides insights into the molecular basis of lung cancer.Genome medicine · 2026Pooled it
- Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.Nature communications · 2024Pooled it
- Single-cell eQTL mapping reveals cell-type-specific genetic regulation in lung cancer.Cell genomics · 2026Article
- Germline Predisposition to Oncogenic Alkylating Damage in Colorectal Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- The role of long non-coding RNAs in lung cancer metastasis: Molecular mechanisms, pathogenesis and clinical implications.Clinical and translational medicine · 2025Review
- Reassessing the validity of using weighted linear models to implement multi-generational GWAS-by-subtraction: a response to Evans et al.BMC research notes · 2025Article
- Genome-wide association study of early-stage non-small cell lung cancer prognosis: a pooled analysis in the International Lung Cancer Consortium.Carcinogenesis · 2025Article
- An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish.Scientific reports · 2025Article
- An epigenetic memory at thebioRxiv : the preprint server for biology · 2024Article
- Single nucleotide variants in lung cancer.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Article
- Age at lung cancer diagnosis in females versus males who never smoke by race and ethnicity.British journal of cancer · 2024Article
- Assessing the causal relationship between 731 immunophenotypes and the risk of lung cancer: a bidirectional mendelian randomization study.BMC cancer · 2024Article
- Article
- Article
- 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
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 14 institutions in 8 countries.
Funding
Abstract
backgroundGermline genetic variation contributes to lung cancer (LC) susceptibility. Previous genome-wide association studies (GWAS) have implicated susceptibility loci involved in smoking behaviors and DNA repair genes, but further work is required to identify susceptibility variants.
methodsTo identify LC susceptibility loci, a family history-based genome-wide association by proxy (GWAx) of LC (48 843 European proxy LC patients, 195 387 controls) was combined with a previous LC GWAS (29 266 patients, 56 450 controls) by meta-analysis. Colocalization was used to explore candidate genes and overlap with existing traits at discovered susceptibility loci. Polygenic risk scores (PRS) were tested within an independent validation cohort (1 666 LC patients vs 6 664 controls) using variants selected from the LC susceptibility loci and a novel selection approach using published GWAS summary statistics. Finally, the effects of the LC PRS on somatic mutational burden were explored in patients whose tumor resections have been profiled by exome (n = 685) and genome sequencing (n = 61). Statistical tests were 2-sided.
resultsThe GWAx-GWAS meta-analysis identified 8 novel LC loci. Colocalization implicated DNA repair genes (CHEK1), metabolic genes (CYP1A1), and smoking propensity genes (CHRNA4 and CHRNB2). PRS analysis demonstrated that these variants, as well as subgenome-wide significant variants related to expression quantitative trait loci and/or smoking propensity, assisted in LC genetic risk prediction (odds ratio = 1.37, 95% confidence interval = 1.29 to 1.45; P < .001). Patients with higher genetic PRS loads of smoking-related variants tended to have higher mutation burdens in their lung tumors.
conclusionsThis study has expanded the number of LC susceptibility loci and provided insights into the molecular mechanisms by which these susceptibility variants contribute to LC development.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.