ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2016
A Novel Pathway-Based Approach Improves Lung Cancer Risk Prediction Using Germline Genetic Variations.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- The current state of polygenic scores for the development of lung cancer: a systematic review and validation in UK Biobank.British journal of cancer · 2026Pooled it
- Predictive performance of risk prediction models for lung cancer incidence in Western and Asian countries: a systematic review and meta-analysis.Scientific reports · 2025Pooled it
- Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations.The Lancet. Respiratory medicine · 2019Pooled it
- The HUNT lung-SNP model: genetic variants plus clinical variables improve lung cancer risk assessment over clinical models.Journal of cancer research and clinical oncology · 2024Article
- Interaction between Continuous Pack-Years Smoked and Polygenic Risk Score on Lung Cancer Risk: Prospective Results from the Framingham Heart Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- Prediction of lung cancer risk in Chinese population with genetic-environment factor using extreme gradient boosting.Cancer medicine · 2022Article
- Functional studies of lung cancer GWAS beyond association.Human molecular genetics · 2022Review
- Integration of Clinical Information and Imputed Aneuploidy Scores to Enhance Relapse Prediction in Early Stage Lung Cancer Patients.AMIA ... Annual Symposium proceedings. AMIA Symposium · 2022Article
- Random effect based tests for multinomial logistic regression in genetic association studies.Genetic epidemiology · 2021Article
- Targeting lung cancer screening to individuals at greatest risk: the role of genetic factors.Journal of medical genetics · 2021Article
- Individual and joint contributions of genetic and methylation risk scores for enhancing lung cancer risk stratification: data from a population-based cohort in Germany.Clinical epigenetics · 2020Article
- SNP eQTL status and eQTL density in the adjacent region of the SNP are associated with its statistical significance in GWA studies.BMC genetics · 2019Article
- Using germline variants to estimate glioma and subtype risks.Neuro-oncology · 2019Article
- Genetic variant of IRAK2 in the toll-like receptor signaling pathway and survival of non-small cell lung cancer.International journal of cancer · 2018Article
- A Decade of GWAS Results in Lung Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2018Review
- Applying Risk Prediction Models to Optimize Lung Cancer Screening: Current Knowledge, Challenges, and Future Directions.Current epidemiology reports · 2017Article
- A lung cancer risk classifier comprising genome maintenance genes measured in normal bronchial epithelial cells.BMC cancer · 2017Article
- Familial Lung Cancer: A Brief History from the Earliest Work to the Most Recent Studies.Genes · 2017Review
- Risk Prediction Using Genome-Wide Association Studies on Type 2 Diabetes.Genomics & informatics · 2016Article
- Pathway-based approach using hierarchical components of collapsed rare variants.Bioinformatics (Oxford, England) · 2016Article
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Funding
Abstract
backgroundAlthough genome-wide association studies (GWAS) have identified many genetic variants that are strongly associated with lung cancer, these variants have low penetrance and serve as poor predictors of lung cancer in individuals. We sought to increase the predictive value of germline variants by considering their cumulative effects in the context of biologic pathways.
methodsFor individuals in the Environment and Genetics in Lung Cancer Etiology study (1,815 cases/1,971 controls), we computed pathway-level susceptibility effects as the sum of relevant SNP variant alleles weighted by their log-additive effects from a separate lung cancer GWAS meta-analysis (7,766 cases/37,482 controls). Logistic regression models based on age, sex, smoking, genetic variants, and principal components of pathway effects and pathway-smoking interactions were trained and optimized in cross-validation and further tested on an independent dataset (556 cases/830 controls). We assessed prediction performance using area under the receiver operating characteristic curve (AUC).
resultsCompared with typical binomial prediction models that have epidemiologic predictors (AUC = 0.607) in addition to top GWAS variants (AUC = 0.617), our pathway-based smoking-interactive multinomial model significantly improved prediction performance in external validation (AUC = 0.656, P < 0.0001).
conclusionsOur biologically informed approach demonstrated a larger increase in AUC over nongenetic counterpart models relative to previous approaches that incorporate variants. IMPACT: This model is the first of its kind to evaluate lung cancer prediction using subtype-stratified genetic effects organized into pathways and interacted with smoking. We propose pathway-exposure interactions as a potentially powerful new contributor to risk inference. Cancer Epidemiol Biomarkers Prev; 25(8); 1208-15. ©2016 AACR.
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