Polygenic risk score as a determinant of risk of keratinocyte cancer in an Australian population‐based cohort

Background Keratinocyte cancer (KC) risk is determined by genetic and environmental factors. Genetic risk can be quantified by polygenic risk scores (PRS), which sum the combined effects of single nucleotide polymorphisms (SNPs). Objectives Our objective here was to evaluate the contribution of the...

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Veröffentlicht in:Journal of the European Academy of Dermatology and Venereology 2022-11, Vol.36 (11), p.2036-2042
Hauptverfasser: Liyanage, U.E., Law, M.H., Antonsson, A., Hughes, M.C.B., Gordon, S., Pols, J.C., Green, A.C.
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container_end_page 2042
container_issue 11
container_start_page 2036
container_title Journal of the European Academy of Dermatology and Venereology
container_volume 36
creator Liyanage, U.E.
Law, M.H.
Antonsson, A.
Hughes, M.C.B.
Gordon, S.
Pols, J.C.
Green, A.C.
description Background Keratinocyte cancer (KC) risk is determined by genetic and environmental factors. Genetic risk can be quantified by polygenic risk scores (PRS), which sum the combined effects of single nucleotide polymorphisms (SNPs). Objectives Our objective here was to evaluate the contribution of the summed genetic score to predict the KC risk in the phenotypically well‐characterized Nambour population. Methods We used PLINK v1.90 to calculate PRS for 432 cases, 566 controls, using 78 genome‐wide independent SNPs that are associated with KC risk. We assessed the association between PRS and KC using logistic regression, stratifying the cohort into three risk groups (high 20%, intermediate 60%, low 20%). Results The fully adjusted model including traditional risk factors (phenotypic and sun exposure‐related), showed a significant 50% increase in odds of KC per standard deviation of PRS (odds ratio (OR) = 1.51; 95% confidence interval (CI) = 1.30–1.76, P = 5.75 × 10−8). Those in the top 20% PRS had over three times the risk of KC of those in the lowest 20% (OR = 3.45; 95% CI = 2.18–5.50, P = 1.5 × 10−7) and higher absolute risk of KC per 100 person‐years of 2.96 compared with 1.34. Area under the ROC curve increased from 0.72 to 0.74 on adding PRS to the fully adjusted model. Conclusions These results show that PRS can enhance the prediction of KC above traditional risk factors.
doi_str_mv 10.1111/jdv.18466
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Genetic risk can be quantified by polygenic risk scores (PRS), which sum the combined effects of single nucleotide polymorphisms (SNPs). Objectives Our objective here was to evaluate the contribution of the summed genetic score to predict the KC risk in the phenotypically well‐characterized Nambour population. Methods We used PLINK v1.90 to calculate PRS for 432 cases, 566 controls, using 78 genome‐wide independent SNPs that are associated with KC risk. We assessed the association between PRS and KC using logistic regression, stratifying the cohort into three risk groups (high 20%, intermediate 60%, low 20%). Results The fully adjusted model including traditional risk factors (phenotypic and sun exposure‐related), showed a significant 50% increase in odds of KC per standard deviation of PRS (odds ratio (OR) = 1.51; 95% confidence interval (CI) = 1.30–1.76, P = 5.75 × 10−8). Those in the top 20% PRS had over three times the risk of KC of those in the lowest 20% (OR = 3.45; 95% CI = 2.18–5.50, P = 1.5 × 10−7) and higher absolute risk of KC per 100 person‐years of 2.96 compared with 1.34. Area under the ROC curve increased from 0.72 to 0.74 on adding PRS to the fully adjusted model. Conclusions These results show that PRS can enhance the prediction of KC above traditional risk factors.</description><identifier>ISSN: 0926-9959</identifier><identifier>EISSN: 1468-3083</identifier><identifier>DOI: 10.1111/jdv.18466</identifier><language>eng</language><ispartof>Journal of the European Academy of Dermatology and Venereology, 2022-11, Vol.36 (11), p.2036-2042</ispartof><rights>2022 European Academy of Dermatology and Venereology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3026-76a2a30aa4c3dc5565f32c7377e0be79ca34f1843b2ac600e60c2638d5cccf693</citedby><cites>FETCH-LOGICAL-c3026-76a2a30aa4c3dc5565f32c7377e0be79ca34f1843b2ac600e60c2638d5cccf693</cites><orcidid>0000-0001-8007-4816 ; 0000-0002-7383-8416 ; 0000-0003-4169-1795 ; 0000-0002-4303-8821 ; 0000-0001-7623-328X ; 0000-0002-2753-4841 ; 0000-0003-4588-4084</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjdv.18466$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjdv.18466$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Liyanage, U.E.</creatorcontrib><creatorcontrib>Law, M.H.</creatorcontrib><creatorcontrib>Antonsson, A.</creatorcontrib><creatorcontrib>Hughes, M.C.B.</creatorcontrib><creatorcontrib>Gordon, S.</creatorcontrib><creatorcontrib>Pols, J.C.</creatorcontrib><creatorcontrib>Green, A.C.</creatorcontrib><title>Polygenic risk score as a determinant of risk of keratinocyte cancer in an Australian population‐based cohort</title><title>Journal of the European Academy of Dermatology and Venereology</title><description>Background Keratinocyte cancer (KC) risk is determined by genetic and environmental factors. Genetic risk can be quantified by polygenic risk scores (PRS), which sum the combined effects of single nucleotide polymorphisms (SNPs). Objectives Our objective here was to evaluate the contribution of the summed genetic score to predict the KC risk in the phenotypically well‐characterized Nambour population. Methods We used PLINK v1.90 to calculate PRS for 432 cases, 566 controls, using 78 genome‐wide independent SNPs that are associated with KC risk. We assessed the association between PRS and KC using logistic regression, stratifying the cohort into three risk groups (high 20%, intermediate 60%, low 20%). Results The fully adjusted model including traditional risk factors (phenotypic and sun exposure‐related), showed a significant 50% increase in odds of KC per standard deviation of PRS (odds ratio (OR) = 1.51; 95% confidence interval (CI) = 1.30–1.76, P = 5.75 × 10−8). Those in the top 20% PRS had over three times the risk of KC of those in the lowest 20% (OR = 3.45; 95% CI = 2.18–5.50, P = 1.5 × 10−7) and higher absolute risk of KC per 100 person‐years of 2.96 compared with 1.34. Area under the ROC curve increased from 0.72 to 0.74 on adding PRS to the fully adjusted model. 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Genetic risk can be quantified by polygenic risk scores (PRS), which sum the combined effects of single nucleotide polymorphisms (SNPs). Objectives Our objective here was to evaluate the contribution of the summed genetic score to predict the KC risk in the phenotypically well‐characterized Nambour population. Methods We used PLINK v1.90 to calculate PRS for 432 cases, 566 controls, using 78 genome‐wide independent SNPs that are associated with KC risk. We assessed the association between PRS and KC using logistic regression, stratifying the cohort into three risk groups (high 20%, intermediate 60%, low 20%). Results The fully adjusted model including traditional risk factors (phenotypic and sun exposure‐related), showed a significant 50% increase in odds of KC per standard deviation of PRS (odds ratio (OR) = 1.51; 95% confidence interval (CI) = 1.30–1.76, P = 5.75 × 10−8). Those in the top 20% PRS had over three times the risk of KC of those in the lowest 20% (OR = 3.45; 95% CI = 2.18–5.50, P = 1.5 × 10−7) and higher absolute risk of KC per 100 person‐years of 2.96 compared with 1.34. Area under the ROC curve increased from 0.72 to 0.74 on adding PRS to the fully adjusted model. Conclusions These results show that PRS can enhance the prediction of KC above traditional risk factors.</abstract><doi>10.1111/jdv.18466</doi><tpages>2042</tpages><orcidid>https://orcid.org/0000-0001-8007-4816</orcidid><orcidid>https://orcid.org/0000-0002-7383-8416</orcidid><orcidid>https://orcid.org/0000-0003-4169-1795</orcidid><orcidid>https://orcid.org/0000-0002-4303-8821</orcidid><orcidid>https://orcid.org/0000-0001-7623-328X</orcidid><orcidid>https://orcid.org/0000-0002-2753-4841</orcidid><orcidid>https://orcid.org/0000-0003-4588-4084</orcidid></addata></record>
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title Polygenic risk score as a determinant of risk of keratinocyte cancer in an Australian population‐based cohort
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