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Smoking as a risk factor for lung cancer in women and men: a systematic review and meta-analysis
  1. Linda M O’Keeffe1,2,
  2. Gemma Taylor1,2,3,4,
  3. Rachel R Huxley5,6,
  4. Paul Mitchell7,
  5. Mark Woodward6,8,9,
  6. Sanne A E Peters8
  1. 1 MRC Integrative Epidemiology Unit at the University of Bristol, Bristol Medical School, University of Bristol, Bristol, UK
  2. 2 Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  3. 3 UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK
  4. 4 Department of Psychology, University of Bath, Bath, UK
  5. 5 College of Science, Health and Engineering, La Trobe University, Melbourne, Australia
  6. 6 The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
  7. 7 Olivia Newton-John Cancer and Wellness Centre, Austin Health and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
  8. 8 The George Institute for Global Health, University of Oxford, Oxford, UK
  9. 9 Department of Epidemiology, John Hopkins University, Baltimore, Maryland, USA
  1. Correspondence to Dr Linda M O’Keeffe; linda.okeeffe{at}


Objectives To investigate the sex-specific association between smoking and lung cancer.

Design Systematic review and meta-analysis.

Data sources We searched PubMed and EMBASE from 1 January 1999 to 15 April 2016 for cohort studies. Cohort studies before 1 January 1999 were retrieved from a previous meta-analysis. Individual participant data from three sources were also available to supplement analyses of published literature.

Eligibility criteria for selecting studies Cohort studies reporting the sex-specific relative risk (RR) of lung cancer associated with smoking.

Results Data from 29 studies representing 99 cohort studies, 7 million individuals and >50 000 incident lung cancer cases were included. The sex-specific RRs and their ratio comparing women with men were pooled using random-effects meta-analysis with inverse-variance weighting. The pooled multiple-adjusted lung cancer RR was 6.99 (95% Confidence Interval (CI) 5.09 to 9.59) in women and 7.33 (95% CI 4.90 to 10.96) in men. The pooled ratio of the RRs was 0.92 (95% CI 0.72 to 1.16; I2=89%; p<0.001), with no evidence of publication bias or differences across major pre-defined participant and study subtypes. The women-to-men ratio of RRs was 0.99 (95% CI 0.65 to 1.52), 1.11 (95% CI 0.75 to 1.64) and 0.94 (95% CI 0.69 to 1.30), for light, moderate and heavy smoking, respectively.

Conclusions Smoking yields similar risks of lung cancer in women compared with men. However, these data may underestimate the true risks of lung cancer among women, as the smoking epidemic has not yet reached full maturity in women. Continued efforts to measure the sex-specific association of smoking and lung cancer are required.

  • smoking
  • systematic review
  • lung cancer
  • sex-specific

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  • LMO’K and GT contributed equally.

  • Contributors LMOK, GT, SAEP, RRH and MW designed the study. LMOK and GT performed systematic searches, retrieved literature and performed data extraction. SAEP performed the analysis of the data. LMOK and GT wrote the first draft of the article. RRH, MW and PM contributed important intellectual content and critical expertise and revisions to the manuscript.

  • Funding The MRC Integrative Epidemiology Unit at the University of Bristol is supported by the University of Bristol and the Medical Research Council [MC_UU_12013/2, MC_UU_12013/3, MC_UU_12013/4, MC_UU_12013/6, MC_UU_12013/9]. LMOK is supported by a UK Medical Research Council Population Health Scientist fellowship (MR/M014509/1). GT is funded by a Cancer Research UK Postdoctoral Fellowship (C56067/A21330). SAEP is supported by a UK Medical Research Council Skills Development Fellowship (MR/P014550/1).

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Technical appendix, statistical code and dataset (of published data only) available from authors on request.

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