Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations
Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/78304 |
| _version_ | 1818027561744072704 |
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| author | Fei Chen Burcu F Darst Ravi K Madduri Alex A Rodriguez Xin Sheng Christopher T Rentsch Caroline Andrews Wei Tang Adam S Kibel Anna Plym Kelly Cho Mohamed Jalloh Serigne Magueye Gueye Lamine Niang Olufemi J Ogunbiyi Olufemi Popoola Akindele O Adebiyi Oseremen I Aisuodionoe-Shadrach Hafees O Ajibola Mustapha A Jamda Olabode P Oluwole Maxwell Nwegbu Ben Adusei Sunny Mante Afua Darkwa-Abrahams James E Mensah Andrew Anthony Adjei Halimatou Diop Joseph Lachance Timothy R Rebbeck Stefan Ambs J Michael Gaziano Amy C Justice David V Conti Christopher A Haiman |
| author_facet | Fei Chen Burcu F Darst Ravi K Madduri Alex A Rodriguez Xin Sheng Christopher T Rentsch Caroline Andrews Wei Tang Adam S Kibel Anna Plym Kelly Cho Mohamed Jalloh Serigne Magueye Gueye Lamine Niang Olufemi J Ogunbiyi Olufemi Popoola Akindele O Adebiyi Oseremen I Aisuodionoe-Shadrach Hafees O Ajibola Mustapha A Jamda Olabode P Oluwole Maxwell Nwegbu Ben Adusei Sunny Mante Afua Darkwa-Abrahams James E Mensah Andrew Anthony Adjei Halimatou Diop Joseph Lachance Timothy R Rebbeck Stefan Ambs J Michael Gaziano Amy C Justice David V Conti Christopher A Haiman |
| author_sort | Fei Chen |
| collection | DOAJ |
| description | Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies.
Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case–control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population.
Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90–100% of the PRS) to the average 40–60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62–3.96), 2.8-fold in African ancestry men (95% CI = 2.59–3.03), and 3.2-fold in Hispanic men (95% CI = 2.64–3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55–60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40–60% PRS category.
Conclusions: Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection.
Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government. |
| first_indexed | 2024-12-10T04:49:52Z |
| format | Article |
| id | doaj.art-357704951c834856af7fc63a759e4c2d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:49:52Z |
| publishDate | 2022-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-357704951c834856af7fc63a759e4c2d2022-12-22T02:01:38ZengeLife Sciences Publications LtdeLife2050-084X2022-07-011110.7554/eLife.78304Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populationsFei Chen0https://orcid.org/0000-0002-1679-9932Burcu F Darst1Ravi K Madduri2https://orcid.org/0000-0003-2130-2887Alex A Rodriguez3Xin Sheng4Christopher T Rentsch5Caroline Andrews6Wei Tang7Adam S Kibel8Anna Plym9Kelly Cho10Mohamed Jalloh11Serigne Magueye Gueye12Lamine Niang13Olufemi J Ogunbiyi14https://orcid.org/0000-0002-8748-2879Olufemi Popoola15Akindele O Adebiyi16Oseremen I Aisuodionoe-Shadrach17Hafees O Ajibola18Mustapha A Jamda19Olabode P Oluwole20Maxwell Nwegbu21Ben Adusei22Sunny Mante23Afua Darkwa-Abrahams24https://orcid.org/0000-0003-0649-3996James E Mensah25Andrew Anthony Adjei26Halimatou Diop27Joseph Lachance28https://orcid.org/0000-0002-4650-3741Timothy R Rebbeck29Stefan Ambs30J Michael Gaziano31Amy C Justice32David V Conti33Christopher A Haiman34https://orcid.org/0000-0002-0097-9971Department of Population and Public Health Sciences, University of Southern California, Los Angeles, United StatesDepartment of Population and Public Health Sciences, University of Southern California, Los Angeles, United States; Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, United StatesArgonne National Laboratory, Lemont, United StatesArgonne National Laboratory, Lemont, United StatesDepartment of Population and Public Health Sciences, University of Southern California, Los Angeles, United StatesYale School of Medicine, New Haven, United States; VA Connecticut Healthcare System, West Haven, United States; London School of Hygiene and Tropical Medicine, London, United KingdomHarvard TH Chan School of Public Health and Division of Population Sciences, Dana Farber Cancer Institute, Boston, United StatesLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, United StatesDepartment of Surgery, Urology Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, United StatesDepartment of Surgery, Urology Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, United StatesVA Boston Healthcare System, Boston, United States; Division of Aging, Brigham and Women's Hospital, Boston, United StatesHôpital Général Idrissa Pouye, Dakar, SenegalHôpital Général Idrissa Pouye, Dakar, SenegalHôpital Général Idrissa Pouye, Dakar, SenegalCollege of Medicine, University of Ibadan and University College Hospital, Ibadan, NigeriaCollege of Medicine, University of Ibadan and University College Hospital, Ibadan, NigeriaCollege of Medicine, University of Ibadan and University College Hospital, Ibadan, NigeriaCollege of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, NigeriaCollege of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, NigeriaCollege of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, NigeriaCollege of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, NigeriaCollege of Health Sciences, University of Abuja, University of Abuja Teaching Hospital and Cancer Science Center, Abuja, Nigeria37 Military Hospital, Accra, Ghana37 Military Hospital, Accra, GhanaKorle-Bu Teaching Hospital, Accra, GhanaKorle-Bu Teaching Hospital, Accra, GhanaKorle-Bu Teaching Hospital, Accra, GhanaLaboratoires Bacteriologie et Virologie, Hôpital Aristide Le Dantec, Dakar, SenegalSchool of Biological Sciences, Georgia Institute of Technology, Atlanta, United StatesHarvard TH Chan School of Public Health and Division of Population Sciences, Dana Farber Cancer Institute, Boston, United StatesLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, United StatesVA Boston Healthcare System, Boston, United States; Division of Aging, Brigham and Women's Hospital, Boston, United States; Department of Medicine, Harvard Medical School, Boston, United StatesYale School of Medicine, New Haven, United States; VA Connecticut Healthcare System, West Haven, United StatesDepartment of Population and Public Health Sciences, University of Southern California, Los Angeles, United StatesDepartment of Population and Public Health Sciences, University of Southern California, Los Angeles, United StatesBackground: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case–control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population. Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90–100% of the PRS) to the average 40–60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62–3.96), 2.8-fold in African ancestry men (95% CI = 2.59–3.03), and 3.2-fold in Hispanic men (95% CI = 2.64–3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55–60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40–60% PRS category. Conclusions: Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection. Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.https://elifesciences.org/articles/78304polygenic risk scoresprostate cancerhealth disparitiesAfrican ancestryHispanicmulti-ancestry |
| spellingShingle | Fei Chen Burcu F Darst Ravi K Madduri Alex A Rodriguez Xin Sheng Christopher T Rentsch Caroline Andrews Wei Tang Adam S Kibel Anna Plym Kelly Cho Mohamed Jalloh Serigne Magueye Gueye Lamine Niang Olufemi J Ogunbiyi Olufemi Popoola Akindele O Adebiyi Oseremen I Aisuodionoe-Shadrach Hafees O Ajibola Mustapha A Jamda Olabode P Oluwole Maxwell Nwegbu Ben Adusei Sunny Mante Afua Darkwa-Abrahams James E Mensah Andrew Anthony Adjei Halimatou Diop Joseph Lachance Timothy R Rebbeck Stefan Ambs J Michael Gaziano Amy C Justice David V Conti Christopher A Haiman Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations eLife polygenic risk scores prostate cancer health disparities African ancestry Hispanic multi-ancestry |
| title | Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations |
| title_full | Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations |
| title_fullStr | Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations |
| title_full_unstemmed | Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations |
| title_short | Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations |
| title_sort | validation of a multi ancestry polygenic risk score and age specific risks of prostate cancer a meta analysis within diverse populations |
| topic | polygenic risk scores prostate cancer health disparities African ancestry Hispanic multi-ancestry |
| url | https://elifesciences.org/articles/78304 |
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