TY - JOUR

T1 - AHRR (cg05575921) Methylation Safely Improves Specificity of Lung Cancer Screening Eligibility Criteria

T2 - A Cohort Study

AU - Jacobsen, Katja Kemp

AU - Schnohr, Peter

AU - Jensen, Gorm Boje

AU - Bojesen, Stig E.

N1 - Publisher Copyright: © 2022 American Association for Cancer Research

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1158/1055-9965.EPI-21-1059

DO - 10.1158/1055-9965.EPI-21-1059

M3 - Journal article

C2 - 35064064

AN - SCOPUS:85128161371

VL - 31

SP - 758

EP - 765

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 4

ER -