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Lung cancer, genetic predisposition and smoking: the Nordic Twin Study of Cancer
  1. Jacob Hjelmborg1,2,
  2. Tellervo Korhonen3,4,5,
  3. Klaus Holst6,
  4. Axel Skytthe1,2,
  5. Eero Pukkala7,8,
  6. Julia Kutschke9,
  7. Jennifer R Harris9,
  8. Lorelei A Mucci10,11,12,
  9. Kaare Christensen1,2,
  10. Kamila Czene13,
  11. Hans-Olov Adami12,13,
  12. Thomas Scheike3,
  13. Jaakko Kaprio9,14
  14. on behalf of the Nordic Twin Study of Cancer (NorTwinCan) collaboration
  1. 1 Department of Epidemiology, Biostatistics and Biodemography, University of Southern Denmark, Odense, Denmark
  2. 2 The Danish Twin Registry, University of Southern Denmark, Odense, Denmark
  3. 3 Department of Public Health, University of Helsinki, Helsinki, Finland
  4. 4 Department of Health, National Institute for Health and Welfare, Helsinki, Finland
  5. 5 Institute of Public Health and Clinical Nutrition, University of Eastern Finland Kuopio, Finland
  6. 6 Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark
  7. 7 Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
  8. 8 School of Health Sciences, University of Tampere, Tampere, Finland
  9. 9 Division of Epidemiology, The Norwegian Institute of Public Health, Oslo, Norway
  10. 10 Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  11. 11 Centre for Public Health Sciences, University of Iceland, Reykjavik, Iceland
  12. 12 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
  13. 13 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  14. 14 Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland
  1. Correspondence to Professor Jaakko Kaprio, Department of Public Health, PO Box 41, University of Helsinki, Helsinki FI-00014, Finland; Jaakko.kaprio{at}helsinki.fi

Abstract

Background We aimed to disentangle genetic and environmental causes in lung cancer while considering smoking status.

Methods Four Nordic twin cohorts (43 512 monozygotic (MZ) and 71 895 same sex dizygotic (DZ) twin individuals) had smoking data before cancer diagnosis. We used time-to-event analyses accounting for censoring and competing risk of death to estimate incidence, concordance risk and heritability of liability to develop lung cancer by smoking status.

Results During a median of 28.5 years of follow-up, we recorded 1508 incident lung cancers. Of the 30 MZ and 28 DZ pairs concordant for lung cancer, nearly all were current smokers at baseline and only one concordant pair was seen among never smokers. Among ever smokers, the case-wise concordance of lung cancer, that is the risk before a certain age conditional on lung cancer in the co-twin before that age, was significantly increased compared with the cumulative incidence for both MZ and DZ pairs. This ratio, the relative recurrence risk, significantly decreased by age for MZ but was constant for DZ pairs. Heritability of lung cancer was 0.41 (95% CI 0.26 to 0.56) for currently smoking and 0.37 (95% CI 0.25 to 0.49) for ever smoking pairs. Among smoking discordant pairs, the pairwise HR for lung cancer of the ever smoker twin compared to the never smoker co-twin was 5.4 (95% CI 2.1 to 14.0) in MZ pairs and 5.0 (95% CI 3.2 to 7.9) in DZ pairs.

Conclusions The contribution of familial effects appears to decrease by age. The discordant pair analysis confirms that smoking causes lung cancer.

  • Lung Cancer
  • Tobacco and the lung

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