{
  "abstract": "Smoking is an established cause of lung cancer (LC), but the relative causal contributions of whether a person ever smokes and how heavily they smoke across histological subtypes remain uncertain. This study investigated the causal effects of smoking status and smoking intensity on major LC subtypes. Two-sample Mendelian randomization (MR) was performed. Genetic instruments were drawn from the GWAS and Sequencing Consortium of Alcohol and Nicotine Use: 85 variants for smoking status, a binary trait contrasting ever with never smokers, and 23 variants for smoking intensity, a continuous trait measuring cigarettes smoked per day. Outcomes were 5 LC phenotypes from FinnGen: non-small cell LC (1627 cases), adenocarcinoma (571), squamous cell carcinoma (365), small cell LC (179), and mesothelioma (133). Inverse-variance weighted regression with multiplicative random effects was the primary estimator, with weighted median, weighted mode, and MR-Egger as sensitivity analyses. Benjamini-Hochberg correction was applied across all ten tests. Analyses used R 4.2.3 with TwoSampleMR 0.7.9. Smoking intensity was causally associated with all 4 smoking-related subtypes: squamous cell carcinoma (odds ratio [OR]: 5.95 per standard deviation increase, 95% confidence interval [CI]: 3.12-11.37), small cell LC (OR: 4.43, 95% CI: 1.60-12.32), non-small cell LC (OR: 3.45, 95% CI: 2.30-5.18), and adenocarcinoma (OR: 2.66, 95% CI: 1.40-5.06). All 4 survived correction for multiple testing and were reproduced by the weighted median and weighted mode estimators. Smoking status showed positive point estimates for all 4 subtypes (OR: 1.40-1.61) but reached only nominal significance for non-small cell LC (OR: 1.51, 95% CI: 1.04-2.19, P = .030), which did not survive correction and was not reproduced by other estimators. Neither exposure was associated with mesothelioma. Smoking intensity shows robust causal effects on all smoking-related LC subtypes, whereas the evidence for smoking status is directionally consistent but considerably weaker. The null finding for mesothelioma, a cancer principally caused by asbestos, supports the specificity of the instruments. These results indicate that reducing consumption among established smokers warrants emphasis alongside preventing uptake.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Family & Community Medicine, College of Medicine, Jazan University, Jazan, Saudi Arabia."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mohammad A Jareebi",
      "orcid": "0000-0002-4525-1191"
    },
    {
      "name": "Ahmad Y Alqassim",
      "orcid": "0000-0002-0170-1437"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dhmwdz8fhbgjv.bib",
  "cited_by": 0,
  "doi": "10.1097/md.0000000000051170",
  "fulltext_url": "https://europepmc.org/articles/PMC13681087",
  "id": "dhmwdz8fhbgjv",
  "issns": [
    "0304-5412",
    "1536-5964"
  ],
  "landing_url": "https://europepmc.org/article/MED/42888622",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Smoking Behavior and Cessation"
    ]
  ],
  "openalex": "W7222503351",
  "pdf_url": "https://europepmc.org/articles/PMC13681087?pdf=render",
  "pmcid": "PMC13681087",
  "pmid": "42888622",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dhmwdz8fhbgjv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42888622",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42888622"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Smoking Behavior and Cessation",
      "subfield": "physiology"
    }
  ],
  "title": "Contributions of smoking behaviour to lung cancer subtypes: A two-sample Mendelian randomization study.",
  "title_text": "Contributions of smoking behaviour to lung cancer subtypes: A two-sample Mendelian randomization study.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/dhmwdz8fhbgjv",
  "venue": "Medicine",
  "versions": []
}