Interleukin-10, interleukin-6 and interferon-γ gene polymorphisms in melanoma patients

Abstract

The immune response against melanoma can be influenced by cytokines with potentially opposite effects on tumour cell growth, such as interleukin-10 (IL10), interleukin-6 (IL6) and interferon-gamma (IFNgamma). Our objective in this study was to investigate whether polymorphisms in the regulatory regions of IL10, IL6 and IFNgamma genes are associated with the development of primary cutaneous melanoma and/or the prognosis of this tumour. We studied genotypic variations at positions -1082, -819 and -592 in the IL10 promoter, -174 in the IL6 promoter and +874 in the IFNgamma intron 1 in 42 melanoma patients and 48 healthy controls. These two populations showed very similar genotypic frequencies for IL10, IL6 and IFNgamma gene polymorphisms. There was a significant increase in the prevalence of IL10 low expression genotypes, specially the ACC/ATA genotype, among patients with a poorer prognosis. In contrast, IL6 promoter and IFNgamma intron 1 gene polymorphisms did not correlate with melanoma prognosis. These data indicate that investigation of polymorphisms in the regulatory regions of IL10, IL6 and INFgamma genes does not seem to be useful for predicting the risk of development of primary cutaneous melanoma. However, IL10 low expression genotypes may be associated with a poorer outcome in melanoma patients.

Prognostic Importance of Single-Nucleotide Polymorphisms in IL-6, IL-10, TGF-β1, IFN-γ, and TNF-α Genes in Chronic Phase Chronic Myeloid Leukemia

“…2). Previous studies indicate that IL-10 could be a preferred survival marker, and our results support this fact (Hempel et al, 1997;Martinez-Escribano et al, 2003;Amirzargar et al, 2005).…”

“…IL-6 is associated with poor prognosis in various malignancies (Deans et al, 2007;DeMichele et al, 2009). Nevertheless, it was reported that this cytokine was not associated with multiple myeloma or primary cutaneous melanoma (Martinez-Escribano et al, 2003;Duch et al, 2007). No data are available on a possible association with CML.…”

The −174 G/C gene polymorphism in interleukin-6 is associated with an aggressive breast cancer phenotype

“…This polymorphism has been implicated in a number of chronic disease conditions including arthritis, coronary heart disease and diabetes (Fishman et al, 1998;Fernandez-Real et al, 2000;Yudkin et al, 2000). In human cancer, the À174 G/C IL-6 polymorphism does not appear to be a risk factor for the development of multiple myeloma or melanoma (Zheng et al, 2000;Martinez-Escribano et al, 2002). Recent data, however, suggest that the C allele is associated with an increased risk of colorectal cancer (Landi et al, 2003).…”

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.…”

“…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.…”