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African‐specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer
Author(s) -
Karunamuni Roshan A.,
HuynhLe MinhPhuong,
Fan Chun C.,
Thompson Wesley,
Eeles Rosalind A.,
KoteJarai Zsofia,
Muir Kenneth,
Lophatana Artitaya,
Tangen Catherine M.,
Goodman Phyllis J.,
Thompson Ian M.,
Blot William J.,
Zheng Wei,
Kibel Adam S.,
Drake Bettina F.,
Cussenot Olivier,
CancelTassin Géraldine,
Menegaux Florence,
Truong Thérèse,
Park Jong Y.,
Lin HuiYi,
Bensen Jeannette T.,
Fontham Elizabeth T. H.,
Mohler James L.,
Taylor Jack A.,
Multigner Luc,
Blanchet Pascal,
Brureau Laurent,
Romana Marc,
Leach Robin J.,
John Esther M.,
Fowke Jay,
Bush William S.,
Aldrich Melinda,
Crawford Dana C.,
Srivastava Shiv,
Cullen Jennifer C.,
Petrovics Gyorgy,
Parent MarieÉlise,
Hu Jennifer J.,
Sanderson Maureen,
Mills Ian G.,
Andreassen Ole A.,
Dale Anders M.,
Seibert Tyler M.
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33282
Subject(s) - single nucleotide polymorphism , prostate cancer , hazard ratio , proportional hazards model , medicine , population , oncology , cancer , demography , genotype , biology , genetics , gene , environmental health , confidence interval , sociology
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.