Journal Article

Influence of interleukin-8 and interleukin-10 on sporadic colon cancer development and progression

Tamara Čačev, Senka Radošević, Šimun Križanac and Sanja Kapitanović

in Carcinogenesis

Volume 29, issue 8, pages 1572-1580
Published in print August 2008 | ISSN: 0143-3334
Published online July 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn164
Influence of interleukin-8 and interleukin-10 on sporadic colon cancer development and progression

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Cytokines produced in the tumour microenvironment have an important role in cancer pathogenesis. Altered cytokine expression may result in increased susceptibility to and/or poor prognosis in certain cancers. Therefore, the aim of this study was to investigate the influence of interleukin (IL)-8 and IL-10 on sporadic colon cancer development and progression. In our study, a statistically significant increase in IL-8 messenger RNA (mRNA) expression and decrease in IL-10 mRNA expression in tumour tissue compared with normal mucous tissue was observed (P = 0.003; P = 1.3 × 10−9). No association was found between IL-8 −251 A/T genotypes and IL-8 mRNA expression in tumour and corresponding normal mucous tissue, as well as susceptibility to sporadic colon cancer. Positive immunohistochemical IL-8 staining was more frequent in moderately and poorly differentiated tumours compared with well-differentiated tumours (P = 0.024). Finally, IL-8 significantly stimulated invasion of HT-29 cells in vitro (P = 0.000172). Significant association of IL-10 −1082 A/G, −819 T/C and −592 A/C genotypes and IL-10 mRNA expression in tumour tissue was observed (P = 0.022; P = 0.013; P = 0.02). Significant association of −819 T/C and −592 A/C genotypes and IL-10 mRNA expression in corresponding normal mucous tissue was observed (P = 0.01; P = 0.04) as well. IL-10 single-nucleotide polymorphism (SNP) promoter genotypes associated with low IL-10 mRNA expression (−819 TT; −592 AA) were also associated with increased risk of sporadic colon cancer compared with high-expression genotypes [odds ratio, 5.53; 95% confidence interval (CI), 1.53–20.1; odds ratio, 4.07; 95% CI, 1.28–12.96]. Positive IL-10 immunohistochemical reaction was more frequent in well-differentiated and moderately differentiated tumours compared with poorly differentiated tumours (P = 0.036). In Dukes’ C tumours, positive IL-10 immunohistochemical reaction was less frequent compared with Dukes’ A and B tumours (P = 0.023). Taken together, our results point to possible tumour promoting role of IL-8 and potential protective role of IL-10 in sporadic colon cancer.

Journal Article.  5932 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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