Assessing lung cancer absolute risk trajectory based on a polygenic risk model
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Assessing lung cancer absolute risk trajectory based on a polygenic risk model. / Hung, Rayjean J.; Warkentin, Matthew T.; Brhane, Yonathan; Chatterjee, Nilanjan; Christiani, David C.; Landi, Maria Teresa; Caporaso, Neil E.; Liu, Geoffrey; Johansson, Mattias; Albanes, Demetrius; Marchand, Loic Le; Tardon, Adonina; Rennert, Gad; Bojesen, Stig E.; Chen, Chu; Field, John K.; Kiemeney, Lambertus A.; Lazarus, Philip; Zienolddiny, Shanbeth; Lam, Stephen; Andrew, Angeline S.; Arnold, Susanne M.; Aldrich, Melinda C.; Bickeboller, Heike; Risch, Angela; Schabath, Matthew B.; McKay, James D.; Brennan, Paul; Amos, Christopher I.
I: Cancer Research, Bind 81, Nr. 6, 2021, s. 1607-1615.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Assessing lung cancer absolute risk trajectory based on a polygenic risk model
AU - Hung, Rayjean J.
AU - Warkentin, Matthew T.
AU - Brhane, Yonathan
AU - Chatterjee, Nilanjan
AU - Christiani, David C.
AU - Landi, Maria Teresa
AU - Caporaso, Neil E.
AU - Liu, Geoffrey
AU - Johansson, Mattias
AU - Albanes, Demetrius
AU - Marchand, Loic Le
AU - Tardon, Adonina
AU - Rennert, Gad
AU - Bojesen, Stig E.
AU - Chen, Chu
AU - Field, John K.
AU - Kiemeney, Lambertus A.
AU - Lazarus, Philip
AU - Zienolddiny, Shanbeth
AU - Lam, Stephen
AU - Andrew, Angeline S.
AU - Arnold, Susanne M.
AU - Aldrich, Melinda C.
AU - Bickeboller, Heike
AU - Risch, Angela
AU - Schabath, Matthew B.
AU - McKay, James D.
AU - Brennan, Paul
AU - Amos, Christopher I.
N1 - Publisher Copyright: © 2021 American Association for Cancer Research Inc.. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Lung cancer is the leading cause of cancer-related death globally. An improved risk stratification strategy can increase efficiency of low-dose CT (LDCT) screening. Here we assessed whether individual's genetic background has clinical utility for risk stratification in the context of LDCT screening. On the basis of 13,119 patients with lung cancer and 10,008 controls with European ancestry in the International Lung Cancer Consortium, we constructed a polygenic risk score (PRS) via 10-fold cross-validation with regularized penalized regression. The performance of risk model integrating PRS, including calibration and ability to discriminate, was assessed using UKBiobank data (N335,931). Absolute risk was estimated on the basis of age-specific lung cancer incidence and all-cause mortality as competing risk. To evaluate its potential clinical utility, the PRS distribution was simulated in the National Lung Screening Trial (N 50,772 participants). The lung cancer ORs for individuals at the top decile of the PRS distribution versus those at bottom 10% was 2.39 [95% confidence interval (CI) 1.92-3.00; P 1.80_10_14] in the validation set (Ptrend 5.26_10_20). The OR per SD of PRS increase was 1.26 (95% CI 1.20-1.32; P 9.69_10_23) for overall lung cancer risk in the validation set. When considering absolute risks, individuals at different PRS deciles showed differential trajectories of 5-year and cumulative absolute risk. The age reaching the LDCT screening recommendation threshold can vary by 4 to 8 years, depending on the individual's genetic background, smoking status, and family history. Collectively, these results suggest that individual's genetic background may inform the optimal lung cancer LDCT screening strategy.
AB - Lung cancer is the leading cause of cancer-related death globally. An improved risk stratification strategy can increase efficiency of low-dose CT (LDCT) screening. Here we assessed whether individual's genetic background has clinical utility for risk stratification in the context of LDCT screening. On the basis of 13,119 patients with lung cancer and 10,008 controls with European ancestry in the International Lung Cancer Consortium, we constructed a polygenic risk score (PRS) via 10-fold cross-validation with regularized penalized regression. The performance of risk model integrating PRS, including calibration and ability to discriminate, was assessed using UKBiobank data (N335,931). Absolute risk was estimated on the basis of age-specific lung cancer incidence and all-cause mortality as competing risk. To evaluate its potential clinical utility, the PRS distribution was simulated in the National Lung Screening Trial (N 50,772 participants). The lung cancer ORs for individuals at the top decile of the PRS distribution versus those at bottom 10% was 2.39 [95% confidence interval (CI) 1.92-3.00; P 1.80_10_14] in the validation set (Ptrend 5.26_10_20). The OR per SD of PRS increase was 1.26 (95% CI 1.20-1.32; P 9.69_10_23) for overall lung cancer risk in the validation set. When considering absolute risks, individuals at different PRS deciles showed differential trajectories of 5-year and cumulative absolute risk. The age reaching the LDCT screening recommendation threshold can vary by 4 to 8 years, depending on the individual's genetic background, smoking status, and family history. Collectively, these results suggest that individual's genetic background may inform the optimal lung cancer LDCT screening strategy.
U2 - 10.1158/0008-5472.CAN-20-1237
DO - 10.1158/0008-5472.CAN-20-1237
M3 - Journal article
C2 - 33472890
AN - SCOPUS:85103759318
VL - 81
SP - 1607
EP - 1615
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 6
ER -
ID: 302204498