Interleukin-10 Promoter Polymorphisms and Susceptibility to Skin Squamous Cell Carcinoma After Renal Transplantation

Abstract

After organ transplantation, susceptibility to cancer is multifactorial, especially for skin carcinomas. Risk factors may include genetic susceptibilities, such as the control of cytokine production. Interleukin-10 is a cytokine that is implicated in tumorigenesis, and it has been shown that polymorphisms in its gene promoter correlate with differential amounts of production. The aim of this study was to investigate a possible association between interleukin-10 gene promoter polymorphisms and the occurrence of skin carcinomas after renal transplantation. Seventy kidney transplant recipients who developed a squamous cell carcinoma or a basal cell carcinoma were examined for polymorphisms in the interleukin-10 gene promoter using polymerase chain reaction based methods. Single base pair mutations were studied at positions -1082, -819, and -592. These patients were compared to 70 healthy controls and to 70 matched renal transplant recipients without cancer. The interleukin-10 secretion capability was tested in a subgroup of 40 of these patients by in vitro stimulation of peripheral mononuclear cells. Interleukin-10 genotypes and haplotypes were differently distributed in kidney transplant recipients who developed a skin carcinoma, but especially a squamous cell carcinoma, with an increased frequency of the GCC haplotype and a decreased frequency of the ATA haplotype. Subsequently, we found a shift in the predicted phenotypes from the low production phenotype to the high production phenotype. Secretion of interleukin-10 was strongly correlated to the production predicted phenotype, and tended to be higher in patients who developed a squamous cell carcinoma than in the others. These results indicate that interleukin-10 gene polymorphisms and interleukin-10 production capability may contribute to the development of skin squamous cell carcinomas after renal transplantation.

IL-10 gene promoter and intron polymorphisms as genetic biomarkers of cervical cancer susceptibility among Tunisians

“…Therefore, we hypothesized that IL-10 expression in CC can be associated with HPV infection, and this could produce an immunosuppressive microenvironment and accelerates tumor growth. has been reported that several important polymorphic sites in the IL-10 gene, appears to be responsible with modulated levels of IL-10 [11][12][13]. The association of IL-10 promoter SNPs with CC has been reported by several studies, but with inconclusive findings [14][15][16][17][18].…”

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.…”

Molecular Signatures Linked With Aggressive Behavior in Basal Cell Carcinoma: A Report of 6 Cases

“…This observation complements the preference of a proinflammatory environment for the development of aggressive BCC. When studying squamous and BCCs Alamartine et al 19 reported that high levels of IL-10 and the corresponding promoter polymorphism were associated with SCC and not with BCC. Our pilot study, albeit a small number of aggressive BCC, has shown that a cytokine genetic profile corresponding to a proinflammatory environment with increased TNF-a concomitant with a decrease in antiinflammatory IL-10 is more prevalent in aggressive BCC.…”

“…Earlier studies on BCC have investigated the role of the TNF-308 G à A polymorphism and the IL-10 gene. 19 These studies reported that the TNF allele haplotype a2b4d5 associated with increased transcription significantly influenced the number of BCC tumors in an individual. 17 In an effort to link the LOH at 9q22 and the presence of TNF-a 2308 and IL-10 21082 polymorphisms to aggressive BCCs, we examined the DNA from 15 nonaggressive and 6 discerningly chosen, aggressive BCCs that were microdissected from formalin-fixed paraffin-embedded tissue sections.…”

“…[15][16][17][18] Likewise, interleukin 10 has been shown to be associated with the development of squamous cell carcinoma and malignant melanoma. 19,20 Several reports have shown that the 2308 G à A SNP in the promoter region of the TNF-a gene is associated with upregulation of transcription and increased level of TNFa protein. 21 Similar studies have indicated that the 21082 G à A SNP in IL-10 correlates with decreased amount of the functional IL-10 protein.…”