# Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma; a study of 684 proved cases

Source: https://onco.cc/key-papers/paper-wynder-graham-tobacco-bronchiogenic-carcinoma-jama-1950/  
OnCo record `paper-wynder-graham-tobacco-bronchiogenic-carcinoma-jama-1950` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

One of the two 1950 studies that first tied cigarettes to lung cancer. Wynder and Graham compared the smoking histories of 684 people with proven lung cancer against people without it, and found heavy smoking almost everywhere in the cancer group.

## Summary

Ernest Wynder and Evarts Graham's case-control study of 684 proven cases of bronchiogenic carcinoma, published in the Journal of the American Medical Association on 27 May 1950. It appeared four months before Doll and Hill's British paper (paper-doll-hill-smoking-lung-cancer-bmj-1950), and the two studies were designed and run independently on two continents; their agreement is the reason the finding was believed.

Europe PMC indexes no abstract for the 1950 article, so OnCo carries no figures from it. Graham, a thoracic surgeon who had performed the first successful pneumonectomy for lung cancer in 1933 and who was himself a heavy smoker, is the reason the paper is remembered as much as cited: he died of lung cancer in 1957. JAMA reprinted the article as a landmark in 1985 (PMID 3889389) and the World Health Organization's Bulletin republished it in 2005.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Tags: lung-evidence
- Journal: Journal of the American Medical Association
- Year: 1950
- DOI: 10.1001/jama.1950.02910390001001
- Authors: Wynder EL, Graham EA.
- Findings: No abstract is indexed on Europe PMC; the design (684 proven cases of bronchiogenic carcinoma with smoking histories, compared against controls) is read from the article itself.
- What it means: Half of the evidence base on which every tobacco control policy in the world rests. Lung cancer was a rare disease at the start of the twentieth century and the commonest cancer killer by its end; this paper and Doll and Hill's are where the cause was named.
- Caveats: Retrospective interview study of hospital patients, with the recall and selection problems that go with that design; the prospective British Doctors Study was built to answer those objections.; Association, not mechanism: the carcinogens in tobacco smoke and the mutational signature they leave were worked out over the following half-century.

## Sources

- JAMA 1950: https://doi.org/10.1001/jama.1950.02910390001001
- PubMed: https://pubmed.ncbi.nlm.nih.gov/15415260/
- JAMA landmark reprint (1985): https://pubmed.ncbi.nlm.nih.gov/3889389/
- WHO Bulletin republication (2005): https://europepmc.org/article/MED/15744408

## Connected records

- key papers: [Doll and Hill 1950: the case-control study that tied smoking to lung cancer](https://onco.cc/key-papers/paper-doll-hill-smoking-lung-cancer-bmj-1950/), [The mortality of doctors in relation to their smoking habits; a preliminary report](https://onco.cc/key-papers/paper-doll-hill-mortality-of-doctors-smoking-bmj-1954/)
- roadmaps: [Cancer prevention roadmap: tobacco control and vaccines → biomarker-guided chemoprevention → interception in carriers](https://onco.cc/roadmaps/prevention-roadmap/), [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)
- cancers: [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- fronts: [Early Detection & Screening](https://onco.cc/fronts/early-detection/), [Prevention & Risk](https://onco.cc/fronts/prevention/)
- terms: [Histology](https://onco.cc/terms/histology/)
- bottlenecks: [Prevention we already have is not deployed](https://onco.cc/bottlenecks/b-prevention-adoption/), [The hardest cancers are found late](https://onco.cc/bottlenecks/b-early-detection/)
- journals: [JAMA](https://onco.cc/journals/jama/)

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