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.

Combined haplotype analysis of the interleukin-19 and -20 genes: relationship to plaque-type psoriasis

“…[21][22][23][24] The genes encoding IL-19 25,26 In psoriasis, certain HLA alleles with a protective effect have been identified. 27 Moreover, IL-10.G polymorphism from the IL-10 promoter region has been identified to be protecting against psoriasis.…”

Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance

“…24,25 The IL10 gene has been implicated in the response to a number of diseases such as hepatitis B, pulmonary tuberculosis, herpes zoster, cutaneous malignant melanoma, hepatocellular carcinoma fibrosis, gastric carcinoma, squamous cell carcinoma, inflammatory bowel disease, and HIV. [26][27][28][29][30][31][32][33][34] The genetic neighbors of IL10 consisting of IL19, IL20, and IL24 also modulate the TH1 and TH2 response, suggesting that these recently discovered loci could also be important in HCV clearance. 35 A number of studies have examined the IL10 promoter region SNPs and their associations with HCV susceptibility as well as resistance to antiviral therapy.…”

Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study

“…20,32,33 Indeed, this is in line with most other publications regarding IL-10 polymorphisms and melanoma. [22][23][24][26][27][28] In contrast, Nagano et al 34 reported that 'low-expression' IL-10 polymorphisms significantly protected from non-melanoma skin cancer. This may indicate that the effects of IL-10 differ in different skin cancer entities.…”

“…Similarly, Nikolova et al 23 reported that the low-producing haplotypes like ATA were significantly increased in melanoma cell lines compared with controls, suggesting an association with melanoma susceptibility. Finally, Howell et al 24 found that the IL-10 À1087AA lowexpression genotype was significantly increased among melanoma patients compared with controls. In addition, this genotype was a risk factor for poor disease outcome.…”

“…Only seven studies investigated the role of proximal IL-10 promoter polymorphisms in melanoma susceptibility and in the course of metastasized melanoma. [22][23][24][25][26][27][28] Martinez-Escribano et al 22 found that the abovementioned proximal IL-10 promoter genotypes (SNPs IL-10 À1087AG , IL-10 À824CT and IL-10 À597AC ) were not associated with melanoma susceptibility. However, IL-10 low-producing haplotypes like ACC/ATA were associated with a shorter survival time and greater tumour thickness.…”