AHRR (cg05575921) Methylation Safely Improves Specificity of Lung Cancer Screening Eligibility Criteria: A Cohort Study

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Background: Screening reduces lung cancer mortality, but specificities of eligibility criteria are low. We tested if leukocyte AHRR (cg05575921) methylation improves specificity of lung cancer screening eligibility criteria. Methods: A total of 9,206 and 5,370 individuals of the 1991 to 1994 and 2001 to 2003 examinations of the Copenhagen City Heart Study, Denmark, were followed for lung cancer within 5 years after examination and mortality. Screening eligibility criteria (DANTE, DLCST, ITALUNG, LUSI, NELSON, NLST, and PLCOM2012) were evaluated, and AHRR (cg05575921) methylation extent at different methylation cut points was added. The model with the lowest number of eligible individuals per 5-year lung cancer was validated within the 2001 to 2003 examination. Results: Eligibility criteria identified risk-groups ranging from 3,182 (DANTE) to 1,641 (ITALUNG) individuals. The positive predictive value was highest for PLCOM2012 (3.2%), while DANTE showed the highest negative predictive value (99.7%). Adding AHRR (cg05575921) methylation led to higher specificities for all criteria. Number of eligible individuals per 5-year lung cancer varied from 38 (NELSON) to 27 (NLST) with AHRR (cg05575921) methylation <55%. This last model led to a 21.9% lower screening burden and increased (P < 0.05) specificity of 84.0%. Findings were reproduced among the 5,334 individuals of the 2001 to 2003 examination. Conclusions: Adding AHRR (cg05575921) methylation on top of current eligibility criteria for lung cancer screening improves specificity by excluding those individuals with the lowest risk. Impact: The results point toward a potential clinical use of AHRR (cg05575921) methylation, which is a cost-effective measurement compared with lung CT scanning, to provide additional predictive risk information to identify eligible smokers for lung cancer screening.

TidsskriftCancer Epidemiology Biomarkers and Prevention
Udgave nummer4
Sider (fra-til)758-765
Antal sider8
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
We acknowledge participants and teams of the Copenhagen City Heart Study. This work was supported by the Independent Research Fund Denmark, Medical Sciences, Region Hovedstaden, Chief Physician Johan Boserup and Lise Boserup’s Fund, and Frederiksberg Hospital, all grants awarded the Copenhagen City Heart Study. The salary of K.K. Jacobsen was supported by grants from Dagmar Marshalls Fund and the Harboe Foundation awarded to K.K. Jacobsen. Grant/award numbers are not applicable.

Publisher Copyright:
© 2022 American Association for Cancer Research

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