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| PMID |
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| TITLE |
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| Polygenic Risk Scores Stratify Keratinocyte Cancer Risk among Solid Organ Transplant Recipients with Chronic Immunosuppression in a High Ultraviolet Radiation Environment. |
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| ABSTRACT |
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| Solid organ transplant recipients (SOTRs) have elevated risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), especially in high ultraviolet (UV) radiation environments. We assessed whether polygenic risk scores (PRSs) can improve prediction of BCC and SCC risks and multiplicity over and above traditional risk factors in SOTRs in a high UV setting. We built PRSs for BCC (N=594,881) and SCC (N=581,431) using UK Biobank and 23andMe datasets, validated them in the Australian QSkin Cohort (N>6,300) and applied them in SOTRs in the STAR Cohort from Queensland, Australia, a high UV environment. About half of the SOTRs with a high genetic risk developed BCC (absolute risk=45.45%, 95%CI=33.14-58.19%), and SCC (absolute risk=44.12%, 95%CI=32.08-56.68%). For both cancers, SOTRs in the top quintile were at >3-fold increased risk relative to the bottom quintile. The respective PRSs improved risk predictions by 2% for BCC (AUCs=0.77 versus 0.75, P=0.0691) and SCC (AUCs=0.84 versus 0.82, P=0.0260), over and above the established risk factors and 19.03% (for BCC) and 18.10% (for SCC) of the SOTRs were reclassified in a high/medium/low risk scenario. The PRSs also added predictive accuracy for tumour multiplicity (BCC R =0.21 vs 0.19, P=3.2 x 10 ; SCC R =0.30 vs 0.27, P=4.6 x 10 ). |
| Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2020/11/29 |
| revised |
2021/03/22 |
| accepted |
2021/03/24 |
| entrez |
2021/06/05 20:10 |
| pubmed |
2021/06/06 06:00 |
| medline |
2021/06/06 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Seviiri M |
|
Seviiri |
Mathias |
M |
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Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia; School of Biomedical Sciences, Faculty of Health, and Centre for Genomics and Personalised Health, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove QLD 4059, Australia. Electronic address: Mathias.Seviiri@qimrberghofer.edu.au. |
| Law MH |
|
Law |
Matthew H |
MH |
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Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia; School of Biomedical Sciences, Faculty of Health, and Centre for Genomics and Personalised Health, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove QLD 4059, Australia. |
| Ong JS |
|
Ong |
Jue Sheng |
JS |
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Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia. |
| Gharahkhani P |
|
Gharahkhani |
Puya |
P |
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Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia. |
| Nyholt DR |
|
Nyholt |
Dale R |
DR |
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School of Biomedical Sciences, Faculty of Health, and Centre for Genomics and Personalised Health, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove QLD 4059, Australia. |
| Hopkins P |
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Hopkins |
Peter |
P |
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Queensland Lung Transplant Services, The Prince Charles Hospital, 627 Rode Road, Chermside QLD 4032, Australia. |
| Chambers D |
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Chambers |
Daniel |
D |
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Queensland Lung Transplant Services, The Prince Charles Hospital, 627 Rode Road, Chermside QLD 4032, Australia. |
| Campbell S |
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Campbell |
Scott |
S |
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Department of Nephrology, The Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102, Australia. |
| Isbel NM |
|
Isbel |
Nicole M |
NM |
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Department of Nephrology, The Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102, Australia. |
| Soyer HP |
|
Soyer |
H Peter |
HP |
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The University of Queensland Diamantina Institute, The University of Queensland, Dermatology Research Centre, 37 Kent St, Woolloongabba QLD 4102, Australia; Department of Dermatology, Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102, Australia. |
| Olsen CM |
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Olsen |
Catherine M |
CM |
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Cancer Control Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia; Faculty of Medicine, University of Queensland, 20 Weightman St, Herston QLD 4006, Australia. |
| Ellis JJ |
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Ellis |
Jonathan J |
JJ |
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The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, 37 Kent St, Woolloongabba QLD 4102, Australia. |
| Whiteman DC |
|
Whiteman |
David C |
DC |
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Cancer Control Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia. |
| Green AC |
|
Green |
Adele C |
AC |
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Population Health Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia; CRUK Manchester Institute and Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom. |
| MacGregor S |
|
MacGregor |
Stuart |
S |
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Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia; School of Biomedical Sciences, Faculty of Health, and Centre for Genomics and Personalised Health, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove QLD 4059, Australia. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: The Journal of investigative dermatology |
| ISOABBREVIATION: J Invest Dermatol |
| YEAR: 2021 |
| MONTH: Jun |
| DAY: 02 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1523-1747 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: J Invest Dermatol |
| COUNTRY: United States |
| ISSNLINKING: 0022-202X |
| NLMUNIQUEID: 0426720 |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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