Association between lung cancer somatic mutations and occupational exposure in never-smokers

Our plain-English summary of Association between lung cancer somatic mutations and occupational exposure in never-smokers, by C. Paris, P. Do, B. Mastroianni, et al (The European Respiratory Journal, 2017).

The study

• Authors: C. Paris, P. Do, B. Mastroianni, A. Dixmier, P. Dumont, E. Pichon, C. Chouaid, B. Coudert, P. Foucher, S. Fraboulet, M. Locatelli-Sanchez, N. Baize, E. Dansin, L. Moreau, M. Vincent, P. Missy, F. Morin, D. Moro-Sibilot, S. Couraud, BioCAST/IFCT-1002 study investigators, to the BioCAST/IFCT- 1002 study
• Journal: The European Respiratory Journal
• Published: 2017;50(4)
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.

Copyright ©ERS 2017.

In plain English

This French study examined whether workplace exposures were linked to genetic changes (somatic mutations) in the lung tumours of lifelong never-smokers (fewer than 100 cigarettes). It used the BioCAST cohort of newly diagnosed non-small cell lung cancer patients enrolled at 75 centres between November 2011 and January 2013. Of 384 patients, 313 were analysed. Exposure was assessed with a 71-item questionnaire, and 21 patients were classed as probably or definitely exposed to asbestos. EGFR mutations were found in 4 of 20 asbestos-exposed patients tested (20%) versus 123 of 277 unexposed patients tested (44%), p=0.033. HER2 mutations were found in 2 of 11 asbestos-exposed patients tested (18%) versus 6 of 162 unexposed patients (4%), p=0.084, a difference the authors called marginally significant. After adjustment for sex, age, passive smoking and body mass index, neither association was statistically significant. The authors concluded that occupational exposure slightly affects the molecular pattern of these lung cancers, and that asbestos-exposed patients have a lower chance of EGFR mutations. They cautioned that some subgroups were very small and that many exposed patients had more than one exposure.

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: Observational multicentre cohort study (case-only analysis of never-smokers with lung cancer, with no comparison group of smokers)
• Who was studied: 313 of 384 lifelong never-smokers with newly diagnosed non-small cell lung cancer, enrolled at 75 centres in metropolitan France from November 1, 2011 to January 31, 2013. Patients were included if they completed the occupational questionnaire and were tested for at least one biomarker. 83% were female and 87% had adenocarcinoma.
• Exposure: Occupational exposure to lung carcinogens, assessed by a 71-item questionnaire. Only probable or definite exposure counted as exposed. 27 patients were exposed to polycyclic aromatic hydrocarbons (PAH), 21 to asbestos (fiber type not specified), 14 to silica, 8 to diesel exhaust fumes, 6 to chrome and 6 to paint. 40 patients had at least one of these exposures.
• Main results:
  • EGFR mutations were less frequent in asbestos-exposed patients than in unexposed patients: 20% versus 44%, p=0.033 (4 of 20 versus 123 of 277 tested).
  • HER2 mutations were more frequent in asbestos-exposed patients than in unexposed patients: 18% versus 4%, p=0.084 (2 of 11 versus 6 of 162 tested). The authors described this as marginally significant.
  • In the unadjusted (crude) analysis, asbestos exposure was associated with lower odds of EGFR mutation: crude odds ratio 0.313 (95% CI 0.102 to 0.960, p=0.042).
  • In the unadjusted analysis, asbestos exposure was associated with higher odds of HER2 mutation: crude odds ratio 5.778 (95% CI 1.019 to 32.775, p=0.048), as given in table 4.
  • After adjustment for sex, age, passive smoking and body mass index, neither asbestos association was statistically significant. For EGFR mutations in asbestos-exposed patients the adjusted odds ratio was 0.376 (p=0.099); for HER2 it was 5.089 (p=0.10).
  • BRAF mutations were found in 13% of asbestos-exposed versus 4% of unexposed patients, a difference that was not statistically significant. KRAS frequency was similar in both groups.
  • No ALK alterations were found in asbestos-exposed patients (0 of 9 tested, versus 20 of 162 unexposed).
  • Silica-exposed patients had a molecular profile very similar to asbestos-exposed patients. 10 of the 21 asbestos-exposed patients were also exposed to silica.
• The authors' conclusion: The authors concluded that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers, and in particular that asbestos-exposed patients have a lower chance of EGFR mutations. They noted that these findings were limited by small sample size and could help form hypotheses for further studies.
• Limitations the authors state:
  • Very small numbers of patients in some exposure and mutation subgroups; for example, only four EGFR mutations were found in asbestos-exposed patients.
  • Most exposed patients (21 of 40) had two or more occupational exposures, making it hard to separate the role of each agent.
  • Exposure was based only on a questionnaire, without biological evidence or measured exposure data.
  • Exposure to environmental radon was not considered.
  • Biomarker testing used different assays and techniques at different centres.
  • Clinicians could stop testing once one mutation was found, which may have introduced selection bias for multiple mutations.
  • Case-only design with no comparison to smokers and no independent cohort to validate the findings.

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, Somatic Mutation, Occupational Exposure, Cohort Study, EGFR, HER2.

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