A First Step toward Personalized Medicine in XXXX : Pharmacogenetics as Predictive Marker of Outcome after Chemotherapy-Based Treatment.

@entity1 @entity632 @entity522 @entity5322 @entity900 @entity22477 @entity4311 @entity12 @entity421
PURPOSE: Overall survival in @entity1 with @entity421 is only 60%. Poor response to chemotherapy is the dominant risk factor for poor survival. Pharmacogenetic research can offer possibilities to optimize treatment and improve outcome. We applied a pathway-based approach to evaluate the cumulative effect of genes involved in the metabolism of @entity900 and @entity632 in relationship to clinical outcome. EXPERIMENTAL DESIGN: We included 126 @entity1 with @entity421 . To comprehensively assess common genetic variation in the 54 genes selected, linkage disequilibrium (LD; r (2) = 0.8)-based tag-single nucleotide polymorphisms (SNP) strategy was used. A final set of 384 SNPs was typed using Illumina Beadarray platform. SNPs significantly associated with 5-year progression-free survival (PFS) were replicated in another 64 @entity1 with @entity421 . RESULTS: We identified five variants in @entity12 , @entity4311 , @entity22477 , @entity522 , and @entity5322 that were associated with 5-year PFS. Risk stratification based on the combined effects of the risk alleles showed a significant improvement of 5-year PFS. @entity1 that carried no or only one risk allele had a 5-year PFS of 100% compared with a 5-year PFS of 84.4% for carriers of two or three risk alleles, 66.7% PFS if a @entity1 carried four to five alleles, and a 5-year PFS of 41.8% for @entity1 with >5 risk alleles (P < 0.001). CONCLUSIONS: We identified several genes that showed association with PFS in @entity1 with @entity421 . These pharmacogenetic risk factors might be useful to predict treatment outcome and to stratify @entity1 immediately after diagnosis and offer the possibility to improve treatment and outcome. Clin Cancer Res; 1-6.   2015 AACR.
