| Literature DB >> 32930425 |
Roshan A Karunamuni1, Minh-Phuong Huynh-Le1, Chun C Fan2, Wesley Thompson3, Rosalind A Eeles4,5, Zsofia Kote-Jarai4, Kenneth Muir6,7, Artitaya Lophatananon6, Catherine M Tangen8, Phyllis J Goodman8, Ian M Thompson9, William J Blot10,11, Wei Zheng10, Adam S Kibel12, Bettina F Drake13, Olivier Cussenot14,15, Géraldine Cancel-Tassin14,15, Florence Menegaux16, Thérèse Truong16, Jong Y Park17, Hui-Yi Lin18, Jeannette T Bensen19,20, Elizabeth T H Fontham18, James L Mohler20,21, Jack A Taylor22,23, Luc Multigner24, Pascal Blanchet25, Laurent Brureau25, Marc Romana26, Robin J Leach27, Esther M John28, Jay Fowke29,30, William S Bush31, Melinda Aldrich32, Dana C Crawford31, Shiv Srivastava33,34, Jennifer C Cullen33,34, Gyorgy Petrovics33,34, Marie-Élise Parent35,36, Jennifer J Hu37, Maureen Sanderson38, Ian G Mills39, Ole A Andreassen40, Anders M Dale41, Tyler M Seibert1,41.
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.Entities:
Keywords: African; genome wide association study; genomics; genotypic ancestry; health disparities; polygenic risk; prostate cancer
Mesh：
Year: 2020 PMID： 32930425 PMCID： PMC8135907 DOI： 10.1002/ijc.33282
Source DB: PubMed Journal: Int J Cancer ISSN： 0020-7136 Impact factor: 7.396