RT Journal Article
SR Electronic
T1 A polygenic risk score for breast cancer in U.S. Latinas and Latin-American women
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 598730
DO 10.1101/598730
A1 Yiwey Shieh
A1 Laura Fejerman
A1 Paul C. Lott
A1 Katie Marker
A1 Sarah D. Sawyer
A1 Donglei Hu
A1 Scott Huntsman
A1 Javier Torres
A1 Magdalena Echeverry
A1 Mabel E. Bohorquez
A1 Juan Carlos Martínez-Chéquer
A1 Guadalupe Polanco-Echeverry
A1 Ana P. Estrada-Florez
A1 Christopher A. Haiman
A1 Esther M. John
A1 Lawrence H. Kushi
A1 Gabriela Torres-Mejía
A1 Tatianna Vidaurre
A1 Jeffrey N. Weitzel
A1 Sandro Casavilca Zambrano
A1 Luis G. Carvajal-Carmona
A1 Elad Ziv
A1 Susan L. Neuhausen
YR 2019
UL http://biorxiv.org/content/early/2019/04/12/598730.abstract
AB Background Over 180 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified; these SNPs can be combined into polygenic risk scores (PRS) to predict breast cancer risk. Since most SNPs were identified in predominantly European populations, little is known about the performance of PRS in non-Europeans. We tested the performance of a 180-SNP PRS in Latinas, a large ethnic group with variable levels of Indigenous American, European, and African ancestry.Methods We conducted a pooled case-control analysis of U.S. Latinas and Latin-American women (4,658 cases, 7,629 controls). We constructed a 180-SNP PRS consisting of SNPs associated with breast cancer risk (p < 5 x 10−8). We evaluated the association between the PRS and breast cancer risk using multivariable logistic regression and assessed discrimination using area under the receiver operating characteristic curve (AUROC). We also assessed PRS performance across quartiles of Indigenous American genetic ancestry.Results Of 180 SNPs tested, 140 showed directionally consistent associations compared with European populations, and 43 were nominally significant (p < 0.05). The PRS was associated with breast cancer risk, with an odds ratio (OR) per standard deviation increment of 1.58 (95% CI 1.52-1.64) and AUCROC of 0.63 (95% CI 0.62 to 0.64). The discrimination of the PRS was similar between the top and bottom quartiles of Indigenous American ancestry.Conclusions The 180-SNP PRS predicts breast cancer risk in Latinas, with similar performance as reported for Europeans. The performance of the PRS did not vary substantially according to Indigenous American ancestry.