Association of single nucleotide polymorphisms in IL8 and IL13 with sunitinib-induced toxicity in patients with metastatic renal cell carcinoma

Eur J Clin Pharmacol. 2015 Dec;71(12):1477-84. doi: 10.1007/s00228-015-1935-7. Epub 2015 Sep 21.


Purpose: Earlier, the association of single nucleotide polymorphisms (SNPs) with toxicity and efficacy of sunitinib has been explored in patients with metastatic renal cell carcinoma (mRCC). Recently, additional SNPs have been suggested as potential biomarkers. We investigated these novel SNPs for association with sunitinib treatment outcome in mRCC patients.

Methods: In this exploratory study, we selected SNPs in genes CYP3A4, NR1I2, POR, IL8, IL13, IL4-R, HIF1A and MET that might possibly be associated with sunitinib treatment outcome. Each SNP was tested for association with progression-free survival (PFS) and overall survival (OS) by Cox-regression analysis and for clinical response and toxicity using logistic regression.

Results: We included 374 patients for toxicity analyses, of which 38 patients with non-clear cell renal cell cancer were excluded from efficacy analyses. The risk for hypertension was increased in the presence of the T allele in IL8 rs1126647 (OR = 1.69, 95 % CI = 1.07-2.67, P = 0.024). The T allele in IL13 rs1800925 was associated with an increase in the risk of leukopenia (OR = 6.76, 95 % CI = 1.35-33.9, P = 0.020) and increased prevalence of any toxicity > grade 2 (OR = 1.75, 95 % CI = 1.06-2.88, P = 0.028). No significant associations were found with PFS, OS or clinical response.

Conclusions: We show that polymorphisms in IL8 rs1126647 and IL13 rs1800925 are associated with sunitinib-induced toxicities. Validation in an independent cohort is required.

Keywords: Metastatic renal cell carcinoma; Progression-free survival; Single nucleotide polymorphism; Sunitinib; Toxicity; Tyrosine kinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Indoles / adverse effects*
  • Indoles / therapeutic use
  • Interleukin-13 / genetics*
  • Interleukin-8 / genetics*
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology
  • Logistic Models
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Polymorphism, Single Nucleotide
  • Pyrroles / adverse effects*
  • Pyrroles / therapeutic use
  • Sunitinib
  • Survival Rate


  • Antineoplastic Agents
  • Indoles
  • Interleukin-13
  • Interleukin-8
  • Pyrroles
  • Sunitinib