Evidence mapPaperPMID 41645249Full record

ArticleBMC medicine2026

Shared genetic architecture of psychoactive substance use and pan-cancer: insights from a large‑scale genome‑wide cross‑trait analysis.

Jiahang Song, Pengzhu Li, Martin Canis, Kristian Unger, Nikolaus Alexander Haas, Olivier Gires

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Article in BMC medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Jiahang Song *Department of Otorhinolaryngology, LMU University Hospital, LMU Munich, Munich, Germany.
Pengzhu Li *Division of Pediatric Cardiology and Intensive Care, University Hospital, LMU Munich, Munich, Germany.
Martin CanisDepartment of Otorhinolaryngology, LMU University Hospital, LMU Munich, Munich, Germany.
Kristian UngerDepartment of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
Nikolaus Alexander HaasDivision of Pediatric Cardiology and Intensive Care, University Hospital, LMU Munich, Munich, Germany.
Olivier GiresDepartment of Otorhinolaryngology, LMU University Hospital, LMU Munich, Munich, Germany. Olivier.gires@med.uni-muenchen.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPsychoactive substance use (PSU) and cancer are frequently observed comorbidities that have reciprocal influences and shared behavioral traits of the affected patients. While, e.g., nicotine and alcohol are major carcinogens in the etiology of lung and head and neck cancers, little is known about a shared overarching genetic architecture of PSU and cancer that may predispose individuals to both illnesses.

methodsLarge-scale genome-wide association study (GWAS) summary data revealed shared genetic architecture between cancer and PSU, including alcohol use dependence (AlcUD) and nicotine use dependence (NicUD). Genetic correlations between PSU and cancer were assessed by linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL). Mendelian randomization (MR) analysis was additionally employed to explore causal associations between PSU and cancer. Moreover, phenome-wide association study (PheWAS) and drug target analysis were utilized to evaluate the safety and therapeutic value of pleiotropic hub genes.

resultsGWAS-based cross-referencing of PSU and cancer identified 34 shared trait pairs with significant genetic correlations and a total of 97 pleiotropic genomic risk loci. Affected loci mapped to genes expressed in the brain cerebellum (n = 109) and included cross-trait pleiotropic hub genes (n = 21). MR analysis further identified causal effects of AlcUD and NicUD on cancer risk. After exclusion of genes at high risk of side effects upon inhibition in a PheWAS, cholinergic receptor nicotinic alpha 2 (CHRNA2), histamine receptor H3 (HRH3), and protein tyrosine kinase 6 (PTK6) were identified as potentially druggable targets.

conclusionsIn summary, we identified a shared genetic architecture comprising pleiotropic cerebellar hub genes linking PSU-cancer trait pairs and described potential interventional drugs.

Indexed as

Genome-Wide Association StudyNeoplasmsPsychotropic DrugsSubstance-Related DisordersGenetic Predisposition to DiseaseHumansLinkage DisequilibriumMendelian Randomization AnalysisPolymorphism, Single NucleotidePsychotropic DrugsCancerCHRNA2GWASHRH3PSU-cancer trait pairsPsychoactive substance use (PSU)PTK6

Identifiers

PMID41645249
PMCPMC12930682

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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 Socratic graph.