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IL-10 promoter polymorphisms influence tumour development in cutaneous malignant melanoma

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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.

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Correspondence to WM Howell.

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This work was supported by a grant from the Association for International Cancer Research, St Andrews, Scotland (No. 99–121).

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Howell, W., Turner, S., Bateman, A. et al. IL-10 promoter polymorphisms influence tumour development in cutaneous malignant melanoma. Genes Immun 2, 25–31 (2001). https://doi.org/10.1038/sj.gene.6363726

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  • DOI: https://doi.org/10.1038/sj.gene.6363726

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