title: IL-10 promoter polymorphisms influence tumour development in cutaneous malignant melanoma.
abstract: Cutaneous malignant melanoma (CMM) is the most serious cutaneous malignancy. CMM patients often develop an immune response to their tumours. Conflicting evidence suggests that IL-10 may contribute to tumour escape from the immune response, but may also have an anti-tumour effect. To distinguish between these models and to determine whether genotypes associated with differential IL-10 expression confer susceptibility to and/or influence prognosis in CMM, 165 CMM patients and 158 controls were genotyped for IL-10 promoter SNPs by ARMS-PCR. The IL-10--1082 AA low expression genotype was increased in incidence among CMM patients (P = 0.04). In addition, IL-10 genotypes showed significant associations with three of four prognostic indicators examined; IL-10--1082 GG (P = 0.02) and -1082, -819 and -592 compound high expression (P = 0.03) genotypes were associated with horizontal (non-invasive) tumour growth; IL-10--1082 AA low expression genotype was associated with more advanced (Stage II-IV) disease (P = 0.04); finally, the IL-10--1082 AA (P = 0.005) and compound low expression (P = 0.009) genotypes were significantly increased in frequency among patients with thicker primary Vertical growth phase tumours. These results indicate that genotypes associated with high levels of IL-10 expression in vitro are protective in CMM, while low expression genotypes are a risk factor for more advanced/poorer prognosis disease and may confer susceptibility to CMM. Although the influence of IL-10 on melanoma development is likely to be complex, these results support recent findings that IL-10 has an anti-tumour effect in CMM, possibly via inhibition of angiogenesis.
authors: Department of Human Genetics, University of Southampton, UK. wmhl@soton.ac.uk
authors: W M
authors: WM
authors: Howell
authors: S J
authors: SJ
authors: Turner
authors: A C
authors: AC
authors: Bateman
authors: J M
authors: JM
authors: Theaker
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008545:Melanoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D017931:DNA Primers; D016753:Interleukin-10