Interleukin-10 Polymorphisms, Cancer Susceptibility and Prognosis

Abstract

Interleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and anti-angiogenic functions and may have both tumour-promoting and -inhibiting properties. A large number of polymorphisms (primarily single nucleotide polymorphisms (SNPs)) have been identified in the IL-10 gene promoter. Convincing evidence that certain of these polymorphisms are associated with differential expression of IL-10 in vitro and in some cases in vivo has been obtained and a number of studies have investigated associations between IL-10 polymorphisms and cancer susceptibility/prognosis. The results from 22 studies in 13 different malignancies are reviewed. In 17 of these studies, positive associations between IL-10 genotype or haplotype and disease susceptibility and/or progression were reported. In some of these cancers genotypes associated with low IL-10 expression were a risk factor for disease or disease progression, while in others genotypes associated with high IL-10 expression were a risk factor. Published findings in breast cancer are as yet conflicting. Most, but not all of the studies reviewed are based on small sample sizes and a limited number of IL-10 polymorphisms. However, the preliminary data obtained thus far indicate that larger studies are required in a number of cancers, in order to confirm initial results, extend studies to include more detailed genotype/haplotype analysis and combine genotype and gene expression studies in the same subjects. Such studies will contribute significantly to our understanding of the biological role of IL-10 in cancer development.

The paradox of IL-10-mediated modulation in cervical cancer

“…Previous studies suggested that increased IL-10 levels may control inflammatory responses and cancer development (8) and constitute a risk factor for carcinogenesis. However, in certain types of cancer, low IL-10 expression may constitute a risk factor for disease or disease progression (9). For example, certain studies have demonstrated that IL-10 has the ability to inhibit tumor growth and metastasis in several types of cancer (10)(11)(12).…”

IL-10 polymorphisms and prostate cancer risk: a meta-analysis

“…12,13,14 Hence, in recent studies, three common polymorphisms in the promoter of the IL-10 gene, À1082 (rs1800896) A4G, À819 (rs1800871) C4T and À592(rs1800872) C4A, have been extensively studied in PCa. 15 However, results of studies that examined the association of the three singlenucleotide polymorphisms (SNPs) to the incidence of PCa have been contradictory. Some studies have found that IL-10 À1082 A4G polymorphism increases the risk of PCa, whereas others failed to confirm this observation.…”

The polymorphism IL-1β T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT

“…Several studies have shown a link between polymorphisms in IL-1b, IL-6, IL-10, COX-2, NF-kB and PPARg and cancer risk. [4][5][6][7][8] They may also be central to the pathogenesis of MM. New treatment strategies directed against these targets are being developed, and inborn variations in these genes may therefore become essential for the effect of such targeted therapy.…”