ArticleNature2008
A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25.
Article in Nature, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01780038 (Smokers' Response to Nicotine Dependence Genotyping), which is not on this map. Cited by 699 papers, 19 of them syntheses that pooled it.
What it found
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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.
Smokers' Response to Nicotine Dependence Genotyping
Who cites it
699 citing papers in PubMed, 19 syntheses or guidelines pooled it, 1,283 citations in OpenAlex.
- Multi-population GWAS meta-analysis identifies bladder cancer susceptibility loci and highlights genetic regulation of smoking-related risk.Nature communications · 2026Pooled it
- Loci on chromosome 20 interact with rs16969968 to influence cigarettes per day in European ancestry individuals.Drug and alcohol dependence · 2024Pooled it
- Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.Nature communications · 2023Pooled it
- Using proteomics and metabolomics to identify therapeutic targets for senescence mediated cancer: genetic complementarity method.Frontiers in endocrinology · 2023Pooled it
- Genetic Analysis of Lung Cancer and the Germline Impact on Somatic Mutation Burden.Journal of the National Cancer Institute · 2022Pooled it
- Pooled it
- Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers.PLoS genetics · 2021Pooled it
- Human papillomavirus and lung cancer: an overview and a meta-analysis.Journal of cancer research and clinical oncology · 2019Pooled it
- From genes to treatments: a systematic review of the pharmacogenetics in smoking cessation.Pharmacogenomics · 2018Pooled it
- Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.Journal of the National Comprehensive Cancer Network : JNCCN · 2018Guideline
- Genetic predisposition to lung cancer: comprehensive literature integration, meta-analysis, and multiple evidence assessment of candidate-gene association studies.Scientific reports · 2017Pooled it
- Genetic variations in cancer-related significantly mutated genes and lung cancer susceptibility.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Pooled it
- Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus.Molecular carcinogenesis · 2017Pooled it
- Functional variants in DCAF4 associated with lung cancer risk in European populations.Carcinogenesis · 2017Pooled it
- Susceptibility loci of CNOT6 in the general mRNA degradation pathway and lung cancer risk-A re-analysis of eight GWASs.Molecular carcinogenesis · 2017Pooled it
- Case-control association mapping by proxy using family history of disease.Nature genetics · 2017Pooled it
- Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus.PloS one · 2017Pooled it
- A Novel Genetic Variant in Long Non-coding RNA Gene NEXN-AS1 is Associated with Risk of Lung Cancer.Scientific reports · 2016Pooled it
- Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis.EBioMedicine · 2016Pooled it
- Review
639 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
65 authors at 20 institutions in 15 countries.
Funding
Abstract
Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.
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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.