Cytokine gene polymorphisms, cancer susceptibility, and prognosis

IL-10 is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions and may have both tumor-promoting and -inhibiting properties. A large number of polymorphisms (primarily single-nucleotide polymorphisms) have been identified in the IL10 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 was obtained, and a number of studies investigated associations between IL10 polymorphisms and cancer susceptibility and prognosis. The results from 22 studies in 13 different malignancies are reviewed. In 17 of these studies, positive associations between IL10 genotype or haplotype and disease susceptibility, progression, or both were reported. In some of these cancers genotypes associated with low IL-10 expression were a risk factor for disease or disease progression, whereas 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 indicate that larger studies are required in a number of cancers to confirm initial results, extend studies to include more detailed genotype and 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.