Cytokine Gene Polymorphisms, Cancer Susceptibility, and Prognosis ,

Abstract

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 IL10 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.

Interleukin-6 and Interleukin-10 Gene Promoter Polymorphisms and Risk of Endemic Burkitt Lymphoma

“…Thus, the observations are conflicting. 12 At a biological level, it seems plausible that variability of IL-10 expression levels could contribute to lymphoma genesis, but we did not identify any significant evidence to link selected IL-10 promoter SNPs (-1082A/G, -819C/T, and -592C/A) and eBL risk.…”

“…37 A number of case-control studies have found associations between IL-10 promoter polymorphisms and the risk of cancers, including B-cell lymphoma. 12,38,39 Other investigations have failed to implicate IL-10 promoter polymorphisms in susceptibility. Thus, the observations are conflicting.…”

“…2,8,9 Although the precise pathogenic mechanisms for eBL have not been fully elucidated, genetic susceptibility has been found to play an important role in the development and progression of BL. 10,11 Polymorphisms in cytokine genes can influence inflammation and immune response to infection and may be related to risk of eBL, 12,13 but they have yet to be well-investigated within the context of epidemiologic studies.…”

Impact of Allogenic and Autologous Transfusion on Immune Function in Patients with Tumors

“…IL-10 is an important anti-inflammatory cytokine and can inhibit anti-tumor immunity of the body: on the one hand, it can inhibit Th1 differentiation and the corresponding cytokine synthesis through the antigen-presenting cells. On the other hand, it can inhibit cytotoxicity of effector cells such as cytotoxic T cells, NK cells and γδT (Howell et al, 2007;Kourea et al, 2008). Increase of IL-10 can cause differentiation of Th0 to shift to Th2, resulting in a poor prognosis in tumor patients.…”

Interleukin 10 rs1800872 T>G Polymorphism was Associated with an Increased Risk of Esophageal Cancer in a Chinese Population

“…The IL10 gene is located on chromosome 1q31-32. Studies have shown that IL10 may be involved in the pathogenesis of many types of cancers (Howell et al, 2007). The maturation of Th1 cells from the naive CD4+ T cell pool is regulated by IL12 (Trinchieri et al, 2003), IL12 exhibits an immunoregulatory impact on T and NK cells by inducing IFN-γ biosynthesis from both cell types, augmenting their proliferation and cytotoxicity (Trinchieri et al, 2003).…”