IL8 polymorphisms and overall survival in pazopanib- or sunitinib-treated patients with renal cell carcinoma Journal Article
| Authors: | Xu, C. F.; Johnson, T.; Garcia-Donas, J.; Choueiri, T. K.; Sternberg, C. N.; Davis, I. D.; Bing, N.; Deen, K. C.; Xue, Z.; McCann, L.; Esteban, E.; Whittaker, J. C.; Spraggs, C. F.; Rodríguez-Antona, C.; Pandite, L. N.; Motzer, R. J. |
| Article Title: | IL8 polymorphisms and overall survival in pazopanib- or sunitinib-treated patients with renal cell carcinoma |
| Abstract: | Background: We evaluated germline single nucleotide polymorphisms (SNPs) for association with overall survival (OS) in pazopanib- or sunitinib-treated patients with advanced renal cell carcinoma (aRCC). Methods: The discovery analysis tested 27 SNPs within 13 genes from a phase III pazopanib trial (N=241, study 1). Suggestive associations were then pursued in two independent datasets: a phase III trial (COMPARZ) comparing pazopanib vs sunitinib (N=729, study 2) and an observational study of sunitinib-treated patients (N=89, study 3). Results: In study 1, four SNPs showed nominally significant association (P≤0.05) with OS; two of these SNPs (rs1126647, rs4073) in IL8 were associated (P≤0.05) with OS in study 2. Because rs1126647 and rs4073 were highly correlated, only rs1126647 was evaluated in study 3, which also showed association (P≤0.05). In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P=8.8×10-5; variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15-1.52), without evidence for heterogeneity of effects between studies or between pazopanib- and sunitinib-treated patients. Conclusions: Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC. These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies. © 2015 Cancer Research UK. All rights reserved. |
| Keywords: | adult; cancer chemotherapy; cancer survival; controlled study; protein expression; treatment outcome; aged; major clinical study; overall survival; single nucleotide polymorphism; sunitinib; cancer patient; follow up; neutrophil count; randomized controlled trial; interleukin 8; genetic association; genotype; gene frequency; hemoglobin; hemoglobin blood level; angiogenesis; renal cell carcinoma; kidney carcinoma; body mass; karnofsky performance status; pazopanib; lactate dehydrogenase; phase 3 clinical trial; pharmacogenetics; observational study; double blind procedure; lactate dehydrogenase blood level; human; male; female; priority journal; article; advanced renal cell carcinoma; il8 polymorphism |
| Journal Title: | British Journal of Cancer |
| Volume: | 112 |
| Issue: | 7 |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-03-31 |
| Start Page: | 1190 |
| End Page: | 1198 |
| Language: | English |
| DOI: | 10.1038/bjc.2015.64 |
| PROVIDER: | scopus |
| PMCID: | PMC4385958 |
| PUBMED: | 25695485 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
