Evaluating the association of multiple single nucleotide polymorphisms with response to gemcitabine and platinum combination chemotherapy in urothelial carcinoma of the bladder Journal Article


Authors: Alanee, S. R.; Shah, S.; Zabor, E. C.; Vijai, J.; Ostrovnaya, I.; Garcia-Grossman, I. R.; Pendse, D. V.; Littman, J.; Regazzi, A. M.; Offit, K.; Bajorin, D. F.
Article Title: Evaluating the association of multiple single nucleotide polymorphisms with response to gemcitabine and platinum combination chemotherapy in urothelial carcinoma of the bladder
Abstract: Objective: To examine germline single nucleotide polymorphisms (SNPs) as markers of response to gemcitabine platinum (GP) combination chemotherapy in urothelial carcinoma (UC). Methods: Saliva or blood was prospectively collected from 216 patients treated with GP for UC of the bladder between 1991 and 2011. Based on reported associations with gemcitabine and cisplatin response or putative mechanisms of gemcitabine or cisplatin/carboplatin activity, we selected SNPs of interest and were able to genotype 59 SNPs (using the SequenomMass ARRAYiPLEX platform) in 261 patients randomly split 2/3 into a training set (n = 174) and 1/3 into a test set (n = 87). Logistic regression was used to test the association between response to GP and SNPs. Results: The median age at diagnosis was 64 years (range: 28 -85) for the discovery set and 67 years (range: 30 -84) for the validation set. Males composed 76% and 69%, and white non-Hispanics composed 88% and 91% of the training and test validation sets, respectively. Three SNPs on GALNTL4 (rs7937567, rs12278731, and rs9988868) and one intergenic SNP (rs1321391) were significantly associated with response to GP in the training set and were used to build a SNP score. However, when assessed in the test set, the SNP score was not significantly associated with response. Conclusion: Multiple SNPs selected from previous studies failed to predict response to GP in this cohort. Larger studies capable of accounting for population-based allele frequency heterogeneity may be required for replication of genetic alterations important to pharmacogenomics.
Keywords: cisplatin; bladder cancer; single nucleotide polymorphisms; radical cystectomy; p53; phase-iii; transitional-cell-carcinoma; prognostic value; pharmacogenomics; genetic-variants; tract tumors; cancer; m-vac chemotherapy
Journal Title: International Journal of Clinical Pharmacology and Therapeutics
Volume: 55
Issue: 3
ISSN: 0946-1965
Publisher: Dustri-Verlag Dr. Karl Feistle  
Date Published: 2017-03-01
Start Page: 203
End Page: 209
Language: English
ACCESSION: WOS:000397939800002
DOI: 10.5414/cp202856
PROVIDER: wos
PUBMED: 28177276
Notes: Article -- Source: Wos
Altmetric Score
MSK Authors
  1. Dean Bajorin
    416 Bajorin
  2. Kenneth Offit
    519 Offit
  3. Emily Craig Zabor
    131 Zabor
  4. Vijai Joseph
    120 Joseph
  5. Sohela Shah
    15 Shah
  6. Ashley Regazzi
    35 Regazzi
  7. Deepa Pendse
    3 Pendse