Prior lung disease and risk of lung cancer in a large prospective study

Our plain-English summary of Prior lung disease and risk of lung cancer in a large prospective study, by A.J. Littman, M.D. Thornquist, E. White, et al (Cancer Causes & Control, 2004).

The study

• Authors: A.J. Littman, M.D. Thornquist, E. White, L.A. Jackson, G.E. Goodman, T.L. Vaughan
• Journal: Cancer Causes & Control
• Published: 2004;15(8):819-27
• Cited by: 85 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: While 75-90% of people who develop lung cancer are smokers, only a small proportion of smokers develop lung cancer. Identifying factors that increase a smoker's risk of developing lung cancer may help scientists to better understand the etiology of lung cancer and more effectively target high-risk groups for screening.

Methods: Information on physician-diagnosed non-malignant lung diseases [asbestosis, asthma, chronic bronchitis or emphysema (CB/E), pneumonia, and tuberculosis] was obtained at baseline from 17,698 men and women involved in CARET, a randomized lung cancer prevention trial of beta-carotene and vitamin A among heavy smokers and asbestos-exposed workers. Hazard ratios for lung cancer were estimated through Cox regression models, after controlling for potential confounding factors, included smoking. Analyses were restricted to former and current smokers.

Results: During a median follow up of 9.1 years, 1028 cases of lung cancer occurred. Those who developed lung cancer were more likely to report a history of CB/E than controls (adjusted HR = 1.29, 95% CI: 1.09-1.53). In subgroup analyses, the association between a history of CB/E and lung cancer was stronger for those who were younger at diagnosis/reference, men in the heavy smoker cohort, former smokers, and those with squamous cell carcinomas. There was little association between a history of other lung diseases and lung cancer.

Conclusions: Smokers with a history of CB/E may be at higher risk of developing lung cancer, independent of their smoking history.

In plain English

This study used data from CARET, a trial that tested beta-carotene and vitamin A for preventing lung cancer in heavy smokers and asbestos-exposed workers. The authors analysed 17,698 former and current smokers who, at entry, reported whether a physician had ever told them they had asbestosis, asthma, chronic bronchitis or emphysema (CB/E), pneumonia or tuberculosis. Over a median follow-up of 9.1 years, 1028 lung cancers were diagnosed. Mesotheliomas were not included. After adjusting for smoking and other factors, only CB/E was linked to a statistically significant higher lung cancer risk (hazard ratio 1.29, 95% CI 1.09 to 1.53), most strongly for squamous cell carcinoma (1.54, 1.09 to 2.18). For asbestosis, analysed only within the asbestos-exposed worker cohort, the hazard ratio was 1.14 (0.86 to 1.51), which was not statistically significant. The authors concluded that smokers with CB/E may be at higher risk of lung cancer independent of smoking history. They noted that diagnoses were self-reported and could not be validated, and that residual confounding by smoking was a concern.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective cohort analysis of participants in a randomized, placebo-controlled lung cancer prevention trial (CARET), using Cox proportional hazards models
• Who was studied: 17,698 men and women who were former or current smokers in CARET. The trial randomized 14,254 heavy smokers (aged 50 to 69, 20 or more pack-years) and 4060 asbestos-exposed workers (all male) at six study centers. Follow-up ran through June 2002. Excluded were 502 people not asked about lung diseases, 133 pilot participants who were never smokers, and nine with insufficient smoking information.
• Exposure: Self-reported, physician-diagnosed lung diseases at baseline: asbestosis, asthma, chronic bronchitis or emphysema (CB/E), pneumonia and tuberculosis. Men in the asbestos-exposed worker cohort had either a chest X-ray positive for asbestos-related changes or significant occupational asbestos exposure beginning at least 15 years before recruitment. Fiber types were not specified. Respiratory symptoms of chronic bronchitis were also examined as a secondary measure.
• Main results:
  • Over a median follow-up of 9.1 years (maximum 16), 1028 confirmed lung cancers occurred in the cohort.
  • For all participants, a history of CB/E was associated with lung cancer after adjustment for smoking and other factors (HR 1.29, 95% CI 1.09 to 1.53). It was the only lung disease with a statistically significantly elevated hazard ratio.
  • For squamous cell carcinoma, the hazard ratio associated with CB/E was 1.54 (95% CI 1.09 to 2.18).
  • Asbestosis, analysed only among individuals in the asbestos-exposed worker cohort, had a hazard ratio for all lung cancers of 1.14 (95% CI 0.86 to 1.51), which was not statistically significant.
  • There was little association between the other lung diseases and lung cancer: asthma HR 1.02 (0.81 to 1.28), pneumonia HR 1.10 (0.96 to 1.27), tuberculosis HR 1.00 (0.65 to 1.54).
  • The CB/E hazard ratio was higher for those diagnosed before age 65 (HR 1.57, 95% CI 1.19 to 2.07) than for those aged 65 or over (HR 1.17, 0.94 to 1.44). For squamous cell carcinoma diagnosed before 65, the HR was 2.90 (1.65 to 5.12).
  • By cohort, the CB/E hazard ratio was 1.52 (1.19 to 1.94) for men in the heavy smoker cohort, 1.14 (0.85 to 1.52) for women in the heavy smoker cohort, and 1.10 (0.76 to 1.61) for men in the asbestos-exposed worker cohort.
  • Excluding people diagnosed or censored within one to five years of baseline made little difference to the hazard ratios.
  • Lung cancer risk was 31% higher (95% CI 1.11 to 1.55) among individuals with symptoms of CB/E than among those without.
  • In models not adjusted for smoking, the hazard ratio for CB/E was 1.48 (95% CI 1.26 to 1.76).
• The authors' conclusion: The authors concluded that smokers with a history of CB/E may be at higher risk of developing lung cancer, independent of their smoking history. They found the association particularly strong for squamous cell carcinoma and persons under 65 at diagnosis, and said further investigation into causal mechanisms is needed.
• Limitations the authors state:
  • Lung disease diagnoses were self-reported, and participants could not distinguish chronic bronchitis from emphysema.
  • The authors were not able to validate the diagnoses.
  • Residual confounding by smoking is a concern, and the dose of cigarette smoke reaching the respiratory tract could not be measured.
  • The timing of lung disease diagnosis relative to study entry was uncertain.
  • A common genetic or environmental factor could lead independently to CB/E and lung cancer.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Etiology, Emphysema, Hazard Ratio, Confounding, Squamous Cell Carcinoma.

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