@article{2c219be377f049e38c76a5108d77ae0b,
title = "African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer",
abstract = "Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.",
keywords = "African, genome wide association study, genomics, genotypic ancestry, health disparities, polygenic risk, prostate cancer",
author = "{UKGPCS Collaborators} and {The PRACTICAL Consortium} and Karunamuni, {Roshan A.} and Huynh-Le, {Minh Phuong} and Fan, {Chun C.} and Wesley Thompson and Eeles, {Rosalind A.} and Zsofia Kote-Jarai and Kenneth Muir and Artitaya Lophatananon and Tangen, {Catherine M.} and Goodman, {Phyllis J.} and Thompson, {Ian M.} and Blot, {William J.} and Wei Zheng and Kibel, {Adam S.} and Drake, {Bettina F.} and Olivier Cussenot and G{\'e}raldine Cancel-Tassin and Florence Menegaux and Th{\'e}r{\`e}se Truong and Park, {Jong Y.} and Lin, {Hui Yi} and Bensen, {Jeannette T.} and Fontham, {Elizabeth T.H.} and Mohler, {James L.} and Taylor, {Jack A.} and Luc Multigner and Pascal Blanchet and Laurent Brureau and Marc Romana and Leach, {Robin J.} and John, {Esther M.} and Jay Fowke and Bush, {William S.} and Melinda Aldrich and Crawford, {Dana C.} and Shiv Srivastava and Cullen, {Jennifer C.} and Gyorgy Petrovics and Parent, {Marie {\'E}lise} and Hu, {Jennifer J.} and Maureen Sanderson and Mills, {Ian G.} and Andreassen, {Ole A.} and Dale, {Anders M.} and Seibert, {Tyler M.}",
note = "Funding Information: All authors declare no personal or financial conflicts of interest for the submitted work except as follows. CCF is a scientific consultant for CorTechs Labs, Inc. RE reports honorarium as a speaker for GU-ASCO meeting in San Francisco Jan 2016, support from Janssen, and honorarium as speaker for RMH-FR meeting Nov 2017. She reports honorarium as a speaker at the University of Chicago invited talk May 2018, and an educational honorarium by Bayer & Ipsen to attend GU Connect “Treatment sequencing for mCRPC patients within the changing landscape of mHSPC” at ESMO Barcelona, September 2019. She reports member of external Expert Committee on the Prostate Dx Advisory Panel. OAA received speaker's honorarium from Lundbeck, and is a consultant for Healthlytix. AMD reports that he was a founder and holds equity in CorTechs Labs Inc., and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc., and the Mohn Medical Imaging and Visualization Centre. He received funding through research grants from GE Healthcare to UCSD. The terms of these arrangements have been reviewed by and approved by UCSD in accordance with its conflict of interest policies. TMS reports honoraria, outside of the present work, from: University of Rochester, Varian Medical Systems, Multimodal Imaging Servcies Corporation; and WebMD. He reports research funding from NIH/NBIB, U.S. Department of Defense, Radiological Society of North America, American Society for Radiation Oncology, and Varian Medical Systems. Funding Information: All authors declare no personal or financial conflicts of interest for the submitted work except as follows. CCF is a scientific consultant for CorTechs Labs, Inc. RE reports honorarium as a speaker for GU‐ASCO meeting in San Francisco Jan 2016, support from Janssen, and honorarium as speaker for RMH‐FR meeting Nov 2017. She reports honorarium as a speaker at the University of Chicago invited talk May 2018, and an educational honorarium by Bayer & Ipsen to attend GU Connect “Treatment sequencing for mCRPC patients within the changing landscape of mHSPC” at ESMO Barcelona, September 2019. She reports member of external Expert Committee on the Prostate Dx Advisory Panel. OAA received speaker's honorarium from Lundbeck, and is a consultant for Healthlytix. AMD reports that he was a founder and holds equity in CorTechs Labs Inc., and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc., and the Mohn Medical Imaging and Visualization Centre. He received funding through research grants from GE Healthcare to UCSD. The terms of these arrangements have been reviewed by and approved by UCSD in accordance with its conflict of interest policies. TMS reports honoraria, outside of the present work, from: University of Rochester, Varian Medical Systems, Multimodal Imaging Servcies Corporation; and WebMD. He reports research funding from NIH/NBIB, U.S. Department of Defense, Radiological Society of North America, American Society for Radiation Oncology, and Varian Medical Systems. Publisher Copyright: {\textcopyright} 2020 Union for International Cancer Control",
year = "2021",
month = jan,
day = "1",
doi = "10.1002/ijc.33282",
language = "English",
volume = "148",
pages = "99--105",
journal = "International Journal of Cancer",
issn = "0020-7136",
number = "1",
}