PURPOSE: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In @entity2 , the use of @entity136 and @entity3003 induces grade 3 or 4 myelosuppression in about a quarter of the @entity1 , while an equal fraction of @entity1 is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for @entity136 / @entity3003 -induced myelosuppression. EXPERIMENTAL DESIGN: We exome sequenced 32 @entity1 that suffered extremely high @entity1398 and @entity882 (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy-Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of @entity137 datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis. RESULTS: A total of 53 genetic variants that differed among these groups were validated in an additional 291 @entity1 and were correlated to the @entity1 ' myelosuppression. In the validation, we identified @entity68905 in @entity68906 (P = 0.0008; OR, 5.2; 95% CI, 1.8-18) as a marker for @entity136 / @entity3003 -induced @entity1398 and @entity68907 in @entity8877 (P = 0.0015; OR, 0.36; 95% CI, 0.17-0.71) as a marker for @entity882 . @entity1 homozygous for the minor allele of @entity68905 had a higher risk of @entity1398 , and for @entity68907 the minor allele was associated with a lower risk for @entity882 . CONCLUSIONS: We have identified two new genetic markers with the potential to predict myelosuppression induced by @entity136 / @entity3003 chemotherapy. Clin Cancer Res; 22(2); 366-73.   2015 AACR.

Using Whole-Exome Sequencing to Identify Genetic Markers for @entity3003 and XXXX -Induced @entity137 .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity8877 :: ('168400', 'Gene') :: ['DDX53'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity882 :: ('MESH:D013921', 'Disease') :: ['thrombocytopenia'] @entity68906 :: ('219983', 'Gene') :: ['OR4D6'] @entity3003 :: ('MESH:D016190', 'Chemical') :: ['carboplatin'] @entity2 :: ('MESH:D008175', 'Disease') :: ['lung cancer'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia'] @entity68905 :: ('rs1453542', 'SNP') :: ['rs1453542'] @entity68907 :: ('rs5925720', 'SNP') :: ['rs5925720'] @entity136 :: ('MESH:C056507', 'Chemical') :: ['gemcitabine']
@entity136 :: (MESH:C056507,Chemical) :: ['Gemcitabine']
