Ontology highlight
ABSTRACT: Purpose
Taxane-induced peripheral neuropathy (TIPN) is an important survivorship issue for many cancer patients. Currently, there are no clinically implemented biomarkers to predict which patients might be at increased risk for TIPN. We present a comprehensive approach to identification of genetic variants to predict TIPN.Experimental design
We performed a genome-wide association study (GWAS) in 3,431 patients from the phase III adjuvant breast cancer trial, ECOG-5103 to compare genotypes with TIPN. We performed candidate validation of top SNPs for TIPN in another phase III adjuvant breast cancer trial, ECOG-1199.Results
When evaluating for grade 3-4 TIPN, 120 SNPs had a P value of <10(-4) from patients of European descent (EA) in ECOG-5103. Thirty candidate SNPs were subsequently tested in ECOG-1199 and SNP rs3125923 was found to be significantly associated with grade 3-4 TIPN (P = 1.7 × 10(-3); OR, 1.8). Race was also a major predictor of TIPN, with patients of African descent (AA) experiencing increased risk of grade 2-4 TIPN (HR, 2.1; P = 5.6 × 10(-16)) and grade 3-4 TIPN (HR, 2.6; P = 1.1 × 10(-11)) compared with others. An SNP in FCAMR, rs1856746, had a trend toward an association with grade 2-4 TIPN in AA patients from the GWAS in ECOG-5103 (OR, 5.5; P = 1.6 × 10(-7)).Conclusions
rs3125923 represents a validated SNP to predict grade 3-4 TIPN. Genetically determined AA race represents the most significant predictor of TIPN.
SUBMITTER: Schneider BP
PROVIDER: S-EPMC4717479 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Schneider Bryan P BP Li Lang L Radovich Milan M Shen Fei F Miller Kathy D KD Flockhart David A DA Jiang Guanglong G Vance Gail G Gardner Laura L Vatta Matteo M Bai Shaochun S Lai Dongbing D Koller Daniel D Zhao Fengmin F O'Neill Anne A Smith Mary Lou ML Railey Elda E White Carol C Partridge Ann A Sparano Joseph J Davidson Nancy E NE Foroud Tatiana T Sledge George W GW
Clinical cancer research : an official journal of the American Association for Cancer Research 20150702 22
<h4>Purpose</h4>Taxane-induced peripheral neuropathy (TIPN) is an important survivorship issue for many cancer patients. Currently, there are no clinically implemented biomarkers to predict which patients might be at increased risk for TIPN. We present a comprehensive approach to identification of genetic variants to predict TIPN.<h4>Experimental design</h4>We performed a genome-wide association study (GWAS) in 3,431 patients from the phase III adjuvant breast cancer trial, ECOG-5103 to compare ...[more]