Association of cytokine gene polymorphisms with malignant melanoma in Caucasian population

Abstract

It has been hypothesized that polymorphisms expected to result in functional changes in cytokine genes may influence susceptibility to cancer, including malignant melanoma (MM). Here, we have screened 24 potentially functional polymorphisms in five cytokine genes by PCR-SBT and PCR-SSP methods in 122 MM cell lines derived from Caucasian patients. The polymorphic positions studied were: TNFA -1031, -863, -857, -851, -574, -376, -308, -238, +488; TGFB1 -988, -800, -509, +869, +915, +652, +673, +713, +788; IL10 -1082, -819, -592; IL6 -174; IFNG -333, +874. The frequencies of cytokine genotypes of melanoma tumours were compared with those published for healthy Caucasians. It was found that TNFA -238 GA, TGFB1 -509 CT, -800 GG, IFNG +874 AT, IL6 -174 GG, IL10 -1082 GA genotypes were significantly decreased, while TNFA -238 AA, -857 CC, TGFB1 -509 TT, IFNG +874 AA, IL6 -174 CC, IL10 -1082 AA, -819 TT, -592 AA genotypes were significantly increased, in MM. This suggests that genotypes provisionally associated with low expression of pro-inflammatory and immunomodulatory TNF-alpha, IFN-gamma and IL-6 and anti-inflammatory IL-10 and TGF-beta1 could be involved in the mechanisms of cancer progression and escape from immunosurveillance.

Transforming Growth Factor Beta-1 C-509T Polymorphism and Cancer Risk: A Meta-analysis of 55 Case-control Studies

“…Characteristics of the included studies were shown in Table 1. With the exception of 5 studies (Nikolova et al, 2007;Li et al, 2008;Saltzman et al, 2008;Guan et al, 2009;Guo et al, 2011), the distribution of genotypes for the C-509T polymorphism in the controls of all studies was consistent with Hardy-Weinberg equilibrium. Quantitative Data Synthesis Overall, there was no association between TGF-β1 C-509T polymorphism and cancer risk in all genetic models (T vs. C: OR=1.01, 95%CI=0.94-1.07; TT vs. CC: OR=1.01, 95%CI=0.89-1.15; CT vs. CC: OR=0.98, 95%CI=0.90-1.06; CT+TT vs. CC: OR=0.98, 95%CI=0.88-1.08; TT vs. CT+CC: OR=1.00, 95%CI=0.91-1.10; Table 2).…”

IL-10 polymorphisms and prostate cancer risk: a meta-analysis

“…9 Previous reports showed that reduced levels of IL10 have been associated with the presence of the IL10 À1082G/À819T/À592A haplotype on the IL-10 gene promoter 10,11 as well as with increased risk of cancer in several populations. 12,13,14 Hence, in recent studies, three common polymorphisms in the promoter of the IL-10 gene, À1082 (rs1800896) A4G, À819 (rs1800871) C4T and À592(rs1800872) C4A, have been extensively studied in PCa. 15 However, results of studies that examined the association of the three singlenucleotide polymorphisms (SNPs) to the incidence of PCa have been contradictory.…”

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.…”

“…However, IL-10 low-producing haplotypes like ACC/ATA were associated with a shorter survival time and greater tumour thickness. 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.…”

“…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.…”