Lung cancer, genetic predisposition and smoking: the Nordic Twin Study of Cancer

Jacob v. B. Hjelmborg, Tellervo Korhonen, Klaus Holst, Axel Skytthe, Eero Pukkala, Julia Kutschke, Jennifer Harris, Lorelei Mucci, Kaare Christensen, Kamila Czene, Hans-Olov Adami, Thomas H Scheike, Jaakko Kaprio

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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.
Original languageEnglish
JournalThorax
Volume72
Issue number11
Pages (from-to)1021-1027
ISSN0040-6376
DOIs
Publication statusPublished - 2017

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Twin Studies
Smoking
Neoplasms
Dizygotic Twins
Incidence

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Hjelmborg, Jacob v. B. ; Korhonen, Tellervo ; Holst, Klaus ; Skytthe, Axel ; Pukkala, Eero ; Kutschke, Julia ; Harris, Jennifer ; Mucci, Lorelei ; Christensen, Kaare ; Czene, Kamila ; Adami, Hans-Olov ; Scheike, Thomas H ; Kaprio, Jaakko. / Lung cancer, genetic predisposition and smoking: the Nordic Twin Study of Cancer. In: Thorax. 2017 ; Vol. 72, No. 11. pp. 1021-1027.
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title = "Lung cancer, genetic predisposition and smoking: the Nordic Twin Study of Cancer",
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.",
author = "Hjelmborg, {Jacob v. B.} and Tellervo Korhonen and Klaus Holst and Axel Skytthe and Eero Pukkala and Julia Kutschke and Jennifer Harris and Lorelei Mucci and Kaare Christensen and Kamila Czene and Hans-Olov Adami and Scheike, {Thomas H} and Jaakko Kaprio",
year = "2017",
doi = "10.1136/thoraxjnl-2015-207921",
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Hjelmborg, JVB, Korhonen, T, Holst, K, Skytthe, A, Pukkala, E, Kutschke, J, Harris, J, Mucci, L, Christensen, K, Czene, K, Adami, H-O, Scheike, TH & Kaprio, J 2017, 'Lung cancer, genetic predisposition and smoking: the Nordic Twin Study of Cancer', Thorax, vol. 72, no. 11, pp. 1021-1027. https://doi.org/10.1136/thoraxjnl-2015-207921

Lung cancer, genetic predisposition and smoking: the Nordic Twin Study of Cancer. / Hjelmborg, Jacob v. B.; Korhonen, Tellervo; Holst, Klaus; Skytthe, Axel; Pukkala, Eero; Kutschke, Julia; Harris, Jennifer; Mucci, Lorelei; Christensen, Kaare; Czene, Kamila; Adami, Hans-Olov; Scheike, Thomas H; Kaprio, Jaakko.

In: Thorax, Vol. 72, No. 11, 2017, p. 1021-1027.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Lung cancer, genetic predisposition and smoking: the Nordic Twin Study of Cancer

AU - Hjelmborg, Jacob v. B.

AU - Korhonen, Tellervo

AU - Holst, Klaus

AU - Skytthe, Axel

AU - Pukkala, Eero

AU - Kutschke, Julia

AU - Harris, Jennifer

AU - Mucci, Lorelei

AU - Christensen, Kaare

AU - Czene, Kamila

AU - Adami, Hans-Olov

AU - Scheike, Thomas H

AU - Kaprio, Jaakko

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

UR - http://thorax.bmjjournals.com/cgi/content/abstract/thoraxjnl-2015-207921v1?ct

U2 - 10.1136/thoraxjnl-2015-207921

DO - 10.1136/thoraxjnl-2015-207921

M3 - Journal article

VL - 72

SP - 1021

EP - 1027

JO - Thorax

JF - Thorax

SN - 0040-6376

IS - 11

ER -