Clinical validation of an integrated risk assessment test incorporating genomic and non-genomic data for sporadic breast cancer in Colombia
IntroductionBreast cancer risk arises from a complex interaction of genetic, environmental, and physiological factors. Integrating Polygenic Risk Scores (PRS) with clinical risk factors can enhance personalized risk prediction, especially in diverse populations like Colombia.ObjectiveTo evaluate the...
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Frontiers Media S.A.
2025-07-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1556907/full |
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| author | Harvy Mauricio Velasco Parra Danny Styvens Cardona Danny Styvens Cardona Cesar Augusto Buitrago Melisa Naranjo Vanegas Sebastián Gutiérrez Hincapié Carolina Jaramillo Jaramillo Alicia Maria Cock-Rada Alicia Maria Cock-Rada Alicia Maria Cock-Rada Alicia Maria Cock-Rada Carolina Benavides Duque Clara Patricia Piedrahita Catalina Bustamante Leonel Andrés González Niño Leonel Andrés González Niño Leonel Andrés González Niño Jen Kintle Scott Kulm Alessandro Bolli Paolo Di Dominico Giordano Botta George B. Busby Juan Pablo Valencia-Arango Juan Pablo Valencia-Arango |
| author_facet | Harvy Mauricio Velasco Parra Danny Styvens Cardona Danny Styvens Cardona Cesar Augusto Buitrago Melisa Naranjo Vanegas Sebastián Gutiérrez Hincapié Carolina Jaramillo Jaramillo Alicia Maria Cock-Rada Alicia Maria Cock-Rada Alicia Maria Cock-Rada Alicia Maria Cock-Rada Carolina Benavides Duque Clara Patricia Piedrahita Catalina Bustamante Leonel Andrés González Niño Leonel Andrés González Niño Leonel Andrés González Niño Jen Kintle Scott Kulm Alessandro Bolli Paolo Di Dominico Giordano Botta George B. Busby Juan Pablo Valencia-Arango Juan Pablo Valencia-Arango |
| author_sort | Harvy Mauricio Velasco Parra |
| collection | DOAJ |
| description | IntroductionBreast cancer risk arises from a complex interaction of genetic, environmental, and physiological factors. Integrating Polygenic Risk Scores (PRS) with clinical risk factors can enhance personalized risk prediction, especially in diverse populations like Colombia.ObjectiveTo evaluate the predictive performance of ancestry-specific PRS combined with clinical and imaging risk factors for breast cancer in Colombian women.MethodsWe developed and validated ancestry-specific PRS using diverse genetic datasets. A cohort of 1,997 Colombian women, including 510 breast cancer cases (25.5%) and 1,487 controls (74.5%), were recruited. Clinical data, such as breast density and family history, were analyzed for predictive ability using the area under the receiver operating characteristic curve (AUC). Participants were categorized into genetic ancestry groups: Admixed American, African, and European. PRS were applied to the cohort and adjusted for clinical factors to assess risk prediction.ResultsBreast density and family history were the strongest individual predictors, with AUCs of 0.66 and 0.64, respectively. Most participants were of Admixed American ancestry (70% of cases, 73% of controls). The combined PRS showed an Odds Ratio per Standard Deviation of 1.56 (95% CI 1.40–1.75) and an AUC of 0.72 (95% CI 0.69–0.74) when adjusted for family history. Incorporating PRS with clinical and imaging data improved the AUC to 0.79 (95% CI 0.76–0.81), significantly enhancing predictive accuracy.ConclusionCombining ancestry-specific PRS with clinical risk factors provides a more accurate approach for breast cancer risk stratification in Colombian women. These findings support the development of precise, population-specific risk assessment models. |
| format | Article |
| id | doaj-art-ad283eb9f2824a00a770301ceb0668ed |
| institution | DOAJ |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-ad283eb9f2824a00a770301ceb0668ed2025-08-20T02:42:03ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-07-011610.3389/fgene.2025.15569071556907Clinical validation of an integrated risk assessment test incorporating genomic and non-genomic data for sporadic breast cancer in ColombiaHarvy Mauricio Velasco Parra0Danny Styvens Cardona1Danny Styvens Cardona2Cesar Augusto Buitrago3Melisa Naranjo Vanegas4Sebastián Gutiérrez Hincapié5Carolina Jaramillo Jaramillo6Alicia Maria Cock-Rada7Alicia Maria Cock-Rada8Alicia Maria Cock-Rada9Alicia Maria Cock-Rada10Carolina Benavides Duque11Clara Patricia Piedrahita12Catalina Bustamante13Leonel Andrés González Niño14Leonel Andrés González Niño15Leonel Andrés González Niño16Jen Kintle17Scott Kulm18Alessandro Bolli19Paolo Di Dominico20Giordano Botta21George B. Busby22Juan Pablo Valencia-Arango23Juan Pablo Valencia-Arango24Personalized Medicine Group, Unidad de Bioentendimiento, Bioscience Center- Ayudas Diagnósticas SURA, Medellín, ColombiaPersonalized Medicine Group, Unidad de Bioentendimiento, Bioscience Center- Ayudas Diagnósticas SURA, Medellín, ColombiaData Science Department, Bioscience Center - Ayudas Diagnósticas SURA, Medellín, ColombiaPersonalized Medicine Group, Unidad de Bioentendimiento, Bioscience Center- Ayudas Diagnósticas SURA, Medellín, ColombiaPersonalized Medicine Group, Unidad de Bioentendimiento, Bioscience Center- Ayudas Diagnósticas SURA, Medellín, ColombiaOmics Science Center, Unidad de Bioentendimiento, Bioscience Center – Ayudas Diagnósticas SURA, Medellín, ColombiaOmics Science Center, Unidad de Bioentendimiento, Bioscience Center – Ayudas Diagnósticas SURA, Medellín, ColombiaPersonalized Medicine Group, Unidad de Bioentendimiento, Bioscience Center- Ayudas Diagnósticas SURA, Medellín, ColombiaData Science Department, Bioscience Center - Ayudas Diagnósticas SURA, Medellín, ColombiaOmics Science Center, Unidad de Bioentendimiento, Bioscience Center – Ayudas Diagnósticas SURA, Medellín, ColombiaAyudas Diagnósticas Sura, Bioscience Center, Medellín, ColombiaClinical Research Group, Bioscience Center – Ayudas Diagnósticas SURA, Medellín, ColombiaMedical imaging & AI in health SURA, Bioscience Center – Ayudas Diagnósticas SURA, Medellín, ColombiaMedical imaging & AI in health SURA, Bioscience Center – Ayudas Diagnósticas SURA, Medellín, ColombiaPersonalized Medicine Group, Unidad de Bioentendimiento, Bioscience Center- Ayudas Diagnósticas SURA, Medellín, ColombiaData Science Department, Bioscience Center - Ayudas Diagnósticas SURA, Medellín, ColombiaOmics Science Center, Unidad de Bioentendimiento, Bioscience Center – Ayudas Diagnósticas SURA, Medellín, ColombiaAllelica Inc., New York, United StatesAllelica Inc., New York, United StatesAllelica Inc., New York, United StatesAllelica Inc., New York, United StatesAllelica Inc., New York, United StatesAllelica Inc., New York, United StatesPersonalized Medicine Group, Unidad de Bioentendimiento, Bioscience Center- Ayudas Diagnósticas SURA, Medellín, ColombiaData Science Department, Bioscience Center - Ayudas Diagnósticas SURA, Medellín, ColombiaIntroductionBreast cancer risk arises from a complex interaction of genetic, environmental, and physiological factors. Integrating Polygenic Risk Scores (PRS) with clinical risk factors can enhance personalized risk prediction, especially in diverse populations like Colombia.ObjectiveTo evaluate the predictive performance of ancestry-specific PRS combined with clinical and imaging risk factors for breast cancer in Colombian women.MethodsWe developed and validated ancestry-specific PRS using diverse genetic datasets. A cohort of 1,997 Colombian women, including 510 breast cancer cases (25.5%) and 1,487 controls (74.5%), were recruited. Clinical data, such as breast density and family history, were analyzed for predictive ability using the area under the receiver operating characteristic curve (AUC). Participants were categorized into genetic ancestry groups: Admixed American, African, and European. PRS were applied to the cohort and adjusted for clinical factors to assess risk prediction.ResultsBreast density and family history were the strongest individual predictors, with AUCs of 0.66 and 0.64, respectively. Most participants were of Admixed American ancestry (70% of cases, 73% of controls). The combined PRS showed an Odds Ratio per Standard Deviation of 1.56 (95% CI 1.40–1.75) and an AUC of 0.72 (95% CI 0.69–0.74) when adjusted for family history. Incorporating PRS with clinical and imaging data improved the AUC to 0.79 (95% CI 0.76–0.81), significantly enhancing predictive accuracy.ConclusionCombining ancestry-specific PRS with clinical risk factors provides a more accurate approach for breast cancer risk stratification in Colombian women. These findings support the development of precise, population-specific risk assessment models.https://www.frontiersin.org/articles/10.3389/fgene.2025.1556907/fullpolygenic risk scorebreast cancerrisk stratificationpredictionepidemiologyColombia |
| spellingShingle | Harvy Mauricio Velasco Parra Danny Styvens Cardona Danny Styvens Cardona Cesar Augusto Buitrago Melisa Naranjo Vanegas Sebastián Gutiérrez Hincapié Carolina Jaramillo Jaramillo Alicia Maria Cock-Rada Alicia Maria Cock-Rada Alicia Maria Cock-Rada Alicia Maria Cock-Rada Carolina Benavides Duque Clara Patricia Piedrahita Catalina Bustamante Leonel Andrés González Niño Leonel Andrés González Niño Leonel Andrés González Niño Jen Kintle Scott Kulm Alessandro Bolli Paolo Di Dominico Giordano Botta George B. Busby Juan Pablo Valencia-Arango Juan Pablo Valencia-Arango Clinical validation of an integrated risk assessment test incorporating genomic and non-genomic data for sporadic breast cancer in Colombia Frontiers in Genetics polygenic risk score breast cancer risk stratification prediction epidemiology Colombia |
| title | Clinical validation of an integrated risk assessment test incorporating genomic and non-genomic data for sporadic breast cancer in Colombia |
| title_full | Clinical validation of an integrated risk assessment test incorporating genomic and non-genomic data for sporadic breast cancer in Colombia |
| title_fullStr | Clinical validation of an integrated risk assessment test incorporating genomic and non-genomic data for sporadic breast cancer in Colombia |
| title_full_unstemmed | Clinical validation of an integrated risk assessment test incorporating genomic and non-genomic data for sporadic breast cancer in Colombia |
| title_short | Clinical validation of an integrated risk assessment test incorporating genomic and non-genomic data for sporadic breast cancer in Colombia |
| title_sort | clinical validation of an integrated risk assessment test incorporating genomic and non genomic data for sporadic breast cancer in colombia |
| topic | polygenic risk score breast cancer risk stratification prediction epidemiology Colombia |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1556907/full |
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