Interleukin-4 and interleukin-4 receptor polymorphisms and colorectal cancer risk

Stefano Landi, Fabio Bottari, Federica Gemignani, Lydie Gioia-Patricola, Elisabeth Guino, Alfonso Osorio, Javier de Oca, Gabriel Capella, Federico Canzian, Victor Moreno

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Abstract

Interleukin-4 (IL-4) and interleukin-4 receptor (IL-4R) modulate inflammation and are associated with the colorectal adenoma-carcinoma progression and the metastatic capacity. IL-4 also causes a dose-dependent reduction of proliferation in colorectal cancer cells. The aim of the study was to evaluate whether genetic variants within IL4 and IL4R could affect the individual risk to develop colorectal cancer. We genotyped all the polymorphisms coding for an aminoacidic change in IL4R and we used a haplotype-tagging SNP approach for IL4. We carried out a case-control association study by genotyping, with the 5′ nuclease assay, two common SNPs within IL4 (-588C > T, Ex1-168G > A) and five SNPs within IL4R (I75V, C431R, S436L, S503P, Q576R) in 377 cases of colorectal cancer and 326 controls from Spain. No statistically significant association between the SNPs investigated and colorectal cancer risk was found, as main effects. When the sub-analyses were carried out, the homozygotes for IL4 -588C > T or for Ex1-168G > A showed an increased risk for colon cancer only, with the odds ratios of 4 (95% CI 0.97-16.6; P-interaction = 0.016 and 4.66 (95% CI 1.16-18.77; P-interaction = 0.023), respectively. Moreover, women showed a significant increased risk associated to the IL4 rare alleles and this was clearly greater than that in men (for Ex1-168G > A: OR = 1.96; 95% CI = 1.11-3.47; P-interaction = 0.006). However, when sub-groups are analysed, the findings should be taken with caution for the weakening of the statistical power.

Original languageEnglish
Pages (from-to)762-768
Number of pages7
JournalEuropean Journal of Cancer
Volume43
Issue number4
DOIs
Publication statusPublished - Mar 2007

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Keywords

  • Colorectal cancer
  • Inflammation
  • Polymorphisms

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Landi, S., Bottari, F., Gemignani, F., Gioia-Patricola, L., Guino, E., Osorio, A., Oca, J. D., Capella, G., Canzian, F., & Moreno, V. (2007). Interleukin-4 and interleukin-4 receptor polymorphisms and colorectal cancer risk. European Journal of Cancer, 43(4), 762-768. https://doi.org/10.1016/j.ejca.2006.10.024