AI Article Synopsis

  • Taxane-induced peripheral neuropathy (TIPN) is a significant concern for cancer patients, and researchers aimed to identify genetic markers that could help predict which patients are at higher risk for developing this condition.
  • A genome-wide association study involving 3,431 patients focused on identifying single nucleotide polymorphisms (SNPs) associated with TIPN, with subsequent validation in another group of patients.
  • The study found that the SNP rs3125923 is significantly linked to severe TIPN, while race, particularly being of African descent, was the most prominent predictor for increased risk of developing TIPN.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717479PMC
http://dx.doi.org/10.1158/1078-0432.CCR-15-0586DOI Listing

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