ArticlePloS one2009
Phase I metabolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 13 of them syntheses that pooled it.
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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.
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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
48 citing papers in PubMed, 13 syntheses or guidelines pooled it, 121 citations in OpenAlex.
- Human genetic factors associated with pneumonia risk, a cue for COVID-19 susceptibility.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2022Pooled it
- From genes to treatments: a systematic review of the pharmacogenetics in smoking cessation.Pharmacogenomics · 2018Pooled it
- Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers.The Cochrane database of systematic reviews · 2017Pooled it
- Association between MPO-463G > A polymorphism and cancer risk: evidence from 60 case-control studies.World journal of surgical oncology · 2017Pooled it
- Review of the Gene-Environment Interaction Literature in Cancer: What Do We Know?Genetic epidemiology · 2016Pooled it
- Association between the CYP1B1 polymorphisms and risk of cancer: a meta-analysis.Molecular genetics and genomics : MGG · 2015Pooled it
- Association of CYP1B1 Leu432Val polymorphism and lung cancer risk: an updated meta-analysis.Lung · 2014Pooled it
- Quantitative assessment of the influence of EPHX1 gene polymorphisms and cancer risk: a meta-analysis with 94,213 subjects.Journal of experimental & clinical cancer research : CR · 2014Pooled it
- Association between myeloperoxidase G-463A polymorphism and lung cancer risk.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Association between MPO 463G>A polymorphism and risk of lung cancer: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Pooled it
- Pharmacogenomics of drug-metabolizing enzymes: a recent update on clinical implications and endogenous effects.The pharmacogenomics journal · 2013Pooled it
- Current evidence on the relationship between CYP1B1 polymorphisms and lung cancer risk: a meta-analysis.Molecular biology reports · 2012Pooled it
- Putative EPHX1 enzyme activity is related with risk of lung and upper aerodigestive tract cancers: a comprehensive meta-analysis.PloS one · 2011Pooled it
- Erlotinib in African Americans with advanced non-small cell lung cancer: a prospective randomized study with genetic and pharmacokinetic analyses.Clinical pharmacology and therapeutics · 2014Trial
- Article
- Association of EGFR gene polymorphisms rs2072454 and rs2227983 with lung cancer susceptibility in a Western Algerian population: a case-control study.Journal of the Egyptian National Cancer Institute · 2026Article
- Genome-wide association studies of coffee intake in UK/US participants of European ancestry uncover cohort-specific genetic associations.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Polymorphisms in the gene encoding CYP1A2 influence prostate cancer risk and progression.Oncology letters · 2023Article
- Cytochrome P450 2A6 whole-gene deletion (CYP2A6*4) polymorphism reduces risk of lung cancer: A meta-analysis.Tobacco induced diseases · 2020Review
- Influence of lifestyle choices on risks of CYP1B1 polymorphisms for prostate cancer.Journal of cellular and molecular medicine · 2018Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Polymorphisms in genes coding for enzymes that activate tobacco lung carcinogens may generate inter-individual differences in lung cancer risk. Previous studies had limited sample sizes, poor exposure characterization, and a few single nucleotide polymorphisms (SNPs) tested in candidate genes. We analyzed 25 SNPs (some previously untested) in 2101 primary lung cancer cases and 2120 population controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) study from six phase I metabolic genes, including cytochrome P450s, microsomal epoxide hydrolase, and myeloperoxidase. We evaluated the main genotype effects and genotype-smoking interactions in lung cancer risk overall and in the major histology subtypes. We tested the combined effect of multiple SNPs on lung cancer risk and on gene expression. Findings were prioritized based on significance thresholds and consistency across different analyses, and accounted for multiple testing and prior knowledge. Two haplotypes in EPHX1 were significantly associated with lung cancer risk in the overall population. In addition, CYP1B1 and CYP2A6 polymorphisms were inversely associated with adenocarcinoma and squamous cell carcinoma risk, respectively. Moreover, the association between CYP1A1 rs2606345 genotype and lung cancer was significantly modified by intensity of cigarette smoking, suggesting an underlying dose-response mechanism. Finally, increasing number of variants at CYP1A1/A2 genes revealed significant protection in never smokers and risk in ever smokers. Results were supported by differential gene expression in non-tumor lung tissue samples with down-regulation of CYP1A1 in never smokers and up-regulation in smokers from CYP1A1/A2 SNPs. The significant haplotype associations emphasize that the effect of multiple SNPs may be important despite null single SNP-associations, and warrants consideration in genome-wide association studies (GWAS). Our findings emphasize the necessity of post-GWAS fine mapping and SNP functional assessment to further elucidate cancer risk associations.
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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.