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Sökning: WFRF:(Lin Xihong) > (2024) > Impact of individua...

Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification

Wang, Xinan (författare)
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, 667 Huntington Ave, MA, Boston, United States
Zhang, Ziwei (författare)
Department of Medical Oncology, Dana-Farber Cancer Institute, MA, Boston, United States
Ding, Yi (författare)
Bioinformatics Interdepartmental Program, University of California, Los Angeles, United States
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Chen, Tony (författare)
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States
Mucci, Lorelei (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States
Albanes, Demetrios (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
Landi, Maria Teresa (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
Caporaso, Neil E. (författare)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States
Lam, Stephen (författare)
Department of Medicine, British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada
Tardon, Adonina (författare)
Faculty of Medicine, University of Oviedo and CIBERESP, Oviedo, Spain
Chen, Chu (författare)
Department of Epidemiology, University of Washington School of Public Health, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
Bojesen, Stig E. (författare)
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
Johansson, Mattias (författare)
Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
Risch, Angela (författare)
Department of Biosciences and Medical Biology, Allergy-Cancer-BioNano Research Centre, University of Salzburg, and Cancer Cluster Salzburg, Salzburg, Austria
Bickeböller, Heike (författare)
Department of Genetic Epidemiology, University Medical Center, Georg August University Göttingen, Göttingen, Germany
Wichmann, H-Erich (författare)
Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University, Munich, Germany
Rennert, Gadi (författare)
Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Carmel, Haifa, Israel
Arnold, Susanne (författare)
Markey Cancer Center, University of Kentucky, KY, Lexington, United States
Brennan, Paul (författare)
Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
McKay, James D. (författare)
Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
Field, John K. (författare)
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Shete, Sanjay S. (författare)
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, TX, Houston, United States
Le Marchand, Loic (författare)
Epidemiology Program, University of Hawaii Cancer Center, HI, Honolulu, United States
Liu, Geoffrey (författare)
Princess Margaret Cancer Centre, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
Andrew, Angeline S. (författare)
Department of Epidemiology, Department of Community and Family Medicine, Dartmouth Geisel School of Medicine, NH, Hanover, United States
Kiemeney, Lambertus A. (författare)
Department for Health Evidence, Department of Urology, Radboud University Medical Center, Nijmegen, Netherlands
Zienolddiny-Narui, Shan (författare)
National Institute of Occupational Health, Oslo, Norway
Behndig, Annelie F., 1963- (författare)
Umeå universitet,Institutionen för folkhälsa och klinisk medicin
Johansson, Mikael (författare)
Umeå universitet,Institutionen för strålningsvetenskaper
Cox, Angie (författare)
Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, United Kingdom
Lazarus, Philip (författare)
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, WA, Spokane, United States
Schabath, Matthew B. (författare)
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, FL, Tampa, United States
Aldrich, Melinda C. (författare)
Department of Medicine, Department of Biomedical Informatics and Department of Thoracic Surgery, Vanderbilt University Medical Center, TN, Nashville, United States
Hung, Rayjean J. (författare)
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Dalla Lana School of Public Health, University of Toronto, ON, Toronto, Canada
Amos, Christopher I. (författare)
Institute for Clinical and Translational Research, Department of Medicine, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, TX, Houston, United States
Lin, Xihong (författare)
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States
Christiani, David C. (författare)
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, 667 Huntington Ave, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States
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Department of Environmental Health, Harvard TH. Chan School of Public Health, Harvard University, 667 Huntington Ave, MA, Boston, United States Department of Medical Oncology, Dana-Farber Cancer Institute, MA, Boston, United States (creator_code:org_t)
BioMed Central (BMC), 2024
2024
Engelska.
Ingår i: Genome Medicine. - : BioMed Central (BMC). - 1756-994X .- 1756-994X. ; 16:1
Relaterad länk:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored.Methods: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold.Results: Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (> 90th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12–3.50, P-value = 4.13 × 10−15) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99–2.49, P-value = 5.70 × 10−46). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72–0.74). Conclusions: Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Cancer control
Genetic epidemiology
Non-small cell lung cancer (NSCLC)
Polygenic risk score (PRSs)
Population science

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