Development and validation of a simple general population lung cancer risk model including AHRR-methylation

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Introduction: Screening reduces lung cancer mortality of high-risk populations. Currently proposed screening eligibility criteria only identify half of those individuals, who later develop lung cancer. This study aimed to develop and validate a sensitive and simple model for predicting 10-year lung cancer risk. Methods: Using the 1991–94 examination of The Copenhagen City Heart Study in Denmark, 6,820 former or current smokers from the general population were followed for lung cancer within 10 years after examination. Logistic regression of baseline variables (age, sex, education, chronic obstructive pulmonary disease, family history of lung cancer, smoking status and cumulative smoking, secondhand smoking, occupational exposures to dust and fume, body mass index, lung function, plasma C-reactive protein, and AHRR(cg05575921) methylation) identified the best predictive model. The model was validated among 3,740 former or current smokers from the 2001-03 examination, also followed for 10 years. A simple risk chart was developed with Poisson regression. Results: Age, sex, education, smoking status, cumulative smoking, and AHRR(cg05575921) methylation identified 65 of 88 individuals who developed lung cancer in the validation cohort. The highest risk group, consisting of less educated men aged >65 with current smoking status and cumulative smoking >20 pack-years, had absolute 10-year risks varying from 4% to 16% by AHRR(cg05575921) methylation. Conclusion: A simple risk chart including age, sex, education, smoking status, cumulative smoking, and AHRR(cg05575921) methylation, identifies individuals with 10-year lung cancer risk from below 1% to 16%. Including AHRR(cg05575921) methylation in the eligibility criteria for screening identifies smokers who would benefit the most from screening.

OriginalsprogEngelsk
Artikelnummer107229
TidsskriftLung Cancer
Vol/bind181
Antal sider7
ISSN0169-5002
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work was supported by the Capital Region of Denmark, Chief Physician Johan Boserup and Lise Boserup's Fund, the Independent Research Fund Denmark, and Bispebjerg and Frederiksberg Hospital. The salary of Katja Kemp Jacobsen was funded by Else and Mogens Wedell-Wedellsborgs Fund, Medical Laboratory Technologists Fund (dbio), Arvid Nielsens Fund and Tømrermester Jørgen Holm and Hustru Elisa F Hansens Fund. A part of the AHRR methylation measurements was supported by Aase and Ejner Danielsens Fund and Fabrikant Einar Willumsens Mindelegat. Grant/award numbers are not applicable.

Publisher Copyright:
© 2023 The Author(s)

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