Cargando…
Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts
BACKGROUND: Previous studies suggest that polygenic risk scores (PRSs) may improve melanoma risk stratification. However, there has been limited independent validation of PRS‐based risk prediction, particularly assessment of calibration (comparing predicted to observed risks). OBJECTIVES: To evaluat...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545863/ https://www.ncbi.nlm.nih.gov/pubmed/34921685 http://dx.doi.org/10.1111/bjd.20956 |
_version_ | 1784804913041113088 |
---|---|
author | Steinberg, Julia Iles, Mark M. Lee, Jin Yee Wang, Xiaochuan Law, Matthew H. Smit, Amelia K. Nguyen‐Dumont, Tu Giles, Graham G. Southey, Melissa C. Milne, Roger L. Mann, Graham J. Bishop, D. Timothy MacInnis, Robert J. Cust, Anne E. |
author_facet | Steinberg, Julia Iles, Mark M. Lee, Jin Yee Wang, Xiaochuan Law, Matthew H. Smit, Amelia K. Nguyen‐Dumont, Tu Giles, Graham G. Southey, Melissa C. Milne, Roger L. Mann, Graham J. Bishop, D. Timothy MacInnis, Robert J. Cust, Anne E. |
author_sort | Steinberg, Julia |
collection | PubMed |
description | BACKGROUND: Previous studies suggest that polygenic risk scores (PRSs) may improve melanoma risk stratification. However, there has been limited independent validation of PRS‐based risk prediction, particularly assessment of calibration (comparing predicted to observed risks). OBJECTIVES: To evaluate PRS‐based melanoma risk prediction in prospective UK and Australian cohorts with European ancestry. METHODS: We analysed invasive melanoma incidence in the UK Biobank (UKB; n = 395 647, 1651 cases) and a case‐cohort nested within the Melbourne Collaborative Cohort Study (MCCS, Australia; n = 4765, 303 cases). Three PRSs were evaluated: 68 single‐nucleotide polymorphisms (SNPs) at 54 loci from a 2020 meta‐analysis (PRS68), 50 SNPs significant in the 2020 meta‐analysis excluding UKB (PRS50) and 45 SNPs at 21 loci known in 2018 (PRS45). Ten‐year melanoma risks were calculated from population‐level cancer registry data by age group and sex, with and without PRS adjustment. RESULTS: Predicted absolute melanoma risks based on age and sex alone underestimated melanoma incidence in the UKB [ratio of expected/observed cases: E/O = 0·65, 95% confidence interval (CI) 0·62–0·68] and MCCS (E/O = 0·63, 95% CI 0·56–0·72). For UKB, calibration was improved by PRS adjustment, with PRS50‐adjusted risks E/O = 0·91, 95% CI 0·87–0·95. The discriminative ability for PRS68‐ and PRS50‐adjusted absolute risks was higher than for risks based on age and sex alone (Δ area under the curve 0·07–0·10, P < 0·0001), and higher than for PRS45‐adjusted risks (Δ area under the curve 0·02–0·04, P < 0·001). CONCLUSIONS: A PRS derived from a larger, more diverse meta‐analysis improves risk prediction compared with an earlier PRS, and might help tailor melanoma prevention and early detection strategies to different risk levels. Recalibration of absolute risks may be necessary for application to specific populations. |
format | Online Article Text |
id | pubmed-9545863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95458632022-10-14 Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts Steinberg, Julia Iles, Mark M. Lee, Jin Yee Wang, Xiaochuan Law, Matthew H. Smit, Amelia K. Nguyen‐Dumont, Tu Giles, Graham G. Southey, Melissa C. Milne, Roger L. Mann, Graham J. Bishop, D. Timothy MacInnis, Robert J. Cust, Anne E. Br J Dermatol Original Articles BACKGROUND: Previous studies suggest that polygenic risk scores (PRSs) may improve melanoma risk stratification. However, there has been limited independent validation of PRS‐based risk prediction, particularly assessment of calibration (comparing predicted to observed risks). OBJECTIVES: To evaluate PRS‐based melanoma risk prediction in prospective UK and Australian cohorts with European ancestry. METHODS: We analysed invasive melanoma incidence in the UK Biobank (UKB; n = 395 647, 1651 cases) and a case‐cohort nested within the Melbourne Collaborative Cohort Study (MCCS, Australia; n = 4765, 303 cases). Three PRSs were evaluated: 68 single‐nucleotide polymorphisms (SNPs) at 54 loci from a 2020 meta‐analysis (PRS68), 50 SNPs significant in the 2020 meta‐analysis excluding UKB (PRS50) and 45 SNPs at 21 loci known in 2018 (PRS45). Ten‐year melanoma risks were calculated from population‐level cancer registry data by age group and sex, with and without PRS adjustment. RESULTS: Predicted absolute melanoma risks based on age and sex alone underestimated melanoma incidence in the UKB [ratio of expected/observed cases: E/O = 0·65, 95% confidence interval (CI) 0·62–0·68] and MCCS (E/O = 0·63, 95% CI 0·56–0·72). For UKB, calibration was improved by PRS adjustment, with PRS50‐adjusted risks E/O = 0·91, 95% CI 0·87–0·95. The discriminative ability for PRS68‐ and PRS50‐adjusted absolute risks was higher than for risks based on age and sex alone (Δ area under the curve 0·07–0·10, P < 0·0001), and higher than for PRS45‐adjusted risks (Δ area under the curve 0·02–0·04, P < 0·001). CONCLUSIONS: A PRS derived from a larger, more diverse meta‐analysis improves risk prediction compared with an earlier PRS, and might help tailor melanoma prevention and early detection strategies to different risk levels. Recalibration of absolute risks may be necessary for application to specific populations. John Wiley and Sons Inc. 2022-03-31 2022-05 /pmc/articles/PMC9545863/ /pubmed/34921685 http://dx.doi.org/10.1111/bjd.20956 Text en © 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Steinberg, Julia Iles, Mark M. Lee, Jin Yee Wang, Xiaochuan Law, Matthew H. Smit, Amelia K. Nguyen‐Dumont, Tu Giles, Graham G. Southey, Melissa C. Milne, Roger L. Mann, Graham J. Bishop, D. Timothy MacInnis, Robert J. Cust, Anne E. Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts |
title | Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts
|
title_full | Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts
|
title_fullStr | Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts
|
title_full_unstemmed | Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts
|
title_short | Independent evaluation of melanoma polygenic risk scores in UK and Australian prospective cohorts
|
title_sort | independent evaluation of melanoma polygenic risk scores in uk and australian prospective cohorts |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545863/ https://www.ncbi.nlm.nih.gov/pubmed/34921685 http://dx.doi.org/10.1111/bjd.20956 |
work_keys_str_mv | AT steinbergjulia independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT ilesmarkm independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT leejinyee independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT wangxiaochuan independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT lawmatthewh independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT smitameliak independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT nguyendumonttu independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT gilesgrahamg independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT southeymelissac independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT milnerogerl independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT manngrahamj independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT bishopdtimothy independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT macinnisrobertj independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts AT custannee independentevaluationofmelanomapolygenicriskscoresinukandaustralianprospectivecohorts |