ArticleCancer research2024
CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Cross-ancestry meta-analysis identifies a GSTP1 variant in the polycyclic aromatic hydrocarbons metabolism-related pathway contributing to colorectal cancer susceptibility.Archives of toxicology · 2026Pooled it
- Genetic evidence for POR-mediated ferroptosis in lung cancer prevention: a causal role of granulocyte modulation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Faster CYP2A6 increases COPD and lung cancer risk by increasing smoking quantity: a mediated mendelian randomization and observational mediation study.Respiratory research · 2026Observational
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- Cigarette smoking combines with genetic variants to regulate FOXN3 and associate with bladder cancer risk.Archives of toxicology · 2026Article
- Clinicopathological characteristics associated with intrapulmonary metastasis rather than single primary lung cancer at first diagnosis: a study based on the Surveillance, Epidemiology, and End Results database using Bayesian networks and structural equation modeling.Translational lung cancer research · 2026Article
- Advancing precision tacrolimus therapy: a systems genetics dissection in BXD platform.Frontiers in immunology · 2026Article
- Influencing factors and prediction of growth heterogeneity in solid nodule non-small cell lung cancer based on artificial intelligence: a prospective study.Translational lung cancer research · 2025Article
- Dehydrocostus Lactone Inhibits Microglia-Mediated Neuroinflammation by Targeting CYP2A6 to Improve Ischemic Brain Injury.CNS neuroscience & therapeutics · 2025Article
- Investigating the role of inflammatory cytokines in mediating the effect of gut microbiota on gastrointestinal cancers: a mendelian randomization study.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Single-cell profiling uncovers the intricate pathological niche diversity in brain, lymph node, bone, and adrenal metastases of lung cancer.Discover oncology · 2025Article
- Oral Yeasts Carriage in Prediabetic Smokers and Nonsmokers.International dental journal · 2025Article
- Integrating genetic and clinical data to predict lung cancer in patients with chronic obstructive pulmonary disease.BMC pulmonary medicine · 2024Article
Corrections and comments
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Authors and funding
45 authors at 20 institutions in 16 countries.
Funding
Abstract
Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen-metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke-exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C>T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers (OR = 0.88, 95% confidence interval = 0.85-0.91, P = 2.18 × 10-16), which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor helicase-like transcription factor. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis. SIGNIFICANCE: The causal pathway connecting CYP2A6 genetic variability and activity, cigarette consumption, and lung cancer susceptibility in smokers highlights the need for behavior modification interventions based on host susceptibility for cancer prevention.
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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.