Interleukin-10 polymorphisms, cancer susceptibility and prognosis.

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.