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Karunamuni RA, Huynh-Le MP, Fan CC, et al. Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24. Prostate Cancer Prostatic Dis. 2021;doi: 10.1038/s41391-021-00403-7.
Karunamuni, R. A., Huynh-Le, M. P., Fan, C. C., Thompson, W., Lui, A., Martinez, M. E., Rose, B. S., Mahal, B., Eeles, R. A., Kote-Jarai, Z., Muir, K., Lophatananon, A., Tangen, C. M., Goodman, P. J., Thompson, I. M., Blot, W. J., Zheng, W., Kibel, A. S., Drake, B. F., Cussenot, O., Cancel-Tassin, G., Menegaux, F., Truong, T., Park, J. Y., Lin, H. Y., Taylor, J. A., Bensen, J. T., Mohler, J. L., Fontham, E. T. H., Multigner, L., Blanchet, P., Brureau, L., Romana, M., Leach, R. J., John, E. M., Fowke, J. H., Bush, W. S., Aldrich, M. C., Crawford, D. C., Cullen, J., Petrovics, G., Parent, M. �. �., Hu, J. J., Sanderson, M., Mills, I. G., Andreassen, O. A., Dale, A. M., & Seibert, T. M. (2021). Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24. Prostate cancer and prostatic diseases, . https://doi.org/10.1038/s41391-021-00403-7
Karunamuni, Roshan A, et al. "Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24." Prostate cancer and prostatic diseases vol. (2021). doi: https://doi.org/10.1038/s41391-021-00403-7
Karunamuni RA, Huynh-Le MP, Fan CC, Thompson W, Lui A, Martinez ME, Rose BS, Mahal B, Eeles RA, Kote-Jarai Z, Muir K, Lophatananon A, Tangen CM, Goodman PJ, Thompson IM, Blot WJ, Zheng W, Kibel AS, Drake BF, Cussenot O, Cancel-Tassin G, Menegaux F, Truong T, Park JY, Lin HY, Taylor JA, Bensen JT, Mohler JL, Fontham ETH, Multigner L, Blanchet P, Brureau L, Romana M, Leach RJ, John EM, Fowke JH, Bush WS, Aldrich MC, Crawford DC, Cullen J, Petrovics G, Parent MÉ, Hu JJ, Sanderson M, Mills IG, Andreassen OA, Dale AM, Seibert TM. Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24. Prostate Cancer Prostatic Dis. 2021 Jun 14; doi: 10.1038/s41391-021-00403-7. Epub 2021 Jun 14. PMID: 34127801; PMCID: PMC8669040.
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Prostate Cancer Prostatic Dis. 2021 Jun 14; doi: 10.1038/s41391-021-00403-7. Epub 2021 Jun 14.

Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24.

Prostate cancer and prostatic diseases

Roshan A Karunamuni, Minh-Phuong Huynh-Le, Chun C Fan, Wesley Thompson, Asona Lui, Maria Elena Martinez, Brent S Rose, Brandon Mahal, Rosalind A Eeles, Zsofia Kote-Jarai, Kenneth Muir, Artitaya Lophatananon, Catherine M Tangen, Phyllis J Goodman, Ian M Thompson, William J Blot, Wei Zheng, Adam S Kibel, Bettina F Drake, Olivier Cussenot, Géraldine Cancel-Tassin, Florence Menegaux, Thérèse Truong, Jong Y Park, Hui-Yi Lin, Jack A Taylor, Jeannette T Bensen, James L Mohler, Elizabeth T H Fontham, Luc Multigner, Pascal Blanchet, Laurent Brureau, Marc Romana, Robin J Leach, Esther M John, Jay H Fowke, William S Bush, Melinda C Aldrich, Dana C Crawford, Jennifer Cullen, Gyorgy Petrovics, Marie-Élise Parent, Jennifer J Hu, Maureen Sanderson, Ian G Mills, Ole A Andreassen, Anders M Dale, Tyler M Seibert

Affiliations

  1. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA. [email protected].
  2. Radiation Oncology, George Washington University, Washington, DC, USA.
  3. Center for Human Development, University of California San Diego, La Jolla, CA, USA.
  4. Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA.
  5. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.
  6. Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
  7. Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
  8. Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, USA.
  9. The Institute of Cancer Research, London, UK.
  10. Royal Marsden NHS Foundation Trust, London, UK.
  11. Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK.
  12. Warwick Medical School, University of Warwick, Coventry, UK.
  13. SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  14. CHRISTUS Santa Rosa Hospital - Medical Center, San Antonio, TX, USA.
  15. Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  16. International Epidemiology Institute, Rockville, MD, USA.
  17. Division of Urologic Surgery, Brigham and Womens Hospital, Boston, MA, USA.
  18. Washington University School of Medicine, St. Louis, MO, USA.
  19. Sorbonne Universite, GRC n°5, AP-HP, Tenon Hospital, Paris, France.
  20. CeRePP, Tenon Hospital, Paris, France.
  21. CESP (UMR 1018), Faculté de Médecine, Université Paris-Saclay, Inserm, Gustave Roussy, Villejuif, France.
  22. Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
  23. School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
  24. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
  25. Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
  26. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  27. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  28. Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  29. Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes, France.
  30. CHU de Pointe-à-Pitre, Univ Antilles, Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Pointe-à-Pitre, France.
  31. UMR Inserm 1134, Biologie Intégrée du Globule Rouge, INSERM/Université Paris Diderot-Université Sorbonne Paris Cité/INTS/Université des Antilles, Guadeloupe, France.
  32. Laboratoire d'Excellence GR-Ex « The red cell: from genesis to death », PRES Sorbonne Paris Cité, Paris, France.
  33. Department of Cell Systems and Anatomy, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
  34. Division of Oncology, Departments of Epidemiology & Population Health and of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  35. Department of Medicine and Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
  36. Division of Epidemiology, Department of Preventive Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA.
  37. Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
  38. Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  39. Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
  40. Center for Prostate Disease Research, Bethesda, MD, USA.
  41. Epidemiology and Biostatistics Unit, Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, QC, Canada.
  42. Department of Social and Preventive Medicine, School of Public Health, University of Montreal, Montreal, QC, Canada.
  43. The University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
  44. Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA.
  45. Center for Cancer Research and Cell Biology, Queen's University of Belfast, Belfast, UK.
  46. NORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway.
  47. Department of Radiology, University of California San Diego, La Jolla, CA, USA.
  48. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA. [email protected].
  49. Department of Radiology, University of California San Diego, La Jolla, CA, USA. [email protected].
  50. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. [email protected].

PMID: 34127801 PMCID: PMC8669040 DOI: 10.1038/s41391-021-00403-7

Abstract

BACKGROUND: We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ.

MATERIALS AND METHODS: Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC.

RESULTS: CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings.

CONCLUSION: We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.

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