Abstract
Inherited promoter polymorphisms of the interleukin (IL)-10 gene resulting in altered IL-10 production may contribute to a genetic susceptibility for melanoma. We investigated the role of a haplotype from distal as well as proximal polymorphic sites [−7400InDel, −6752AT (rs6676671), −3538AT (rs1800890), −1087AG (rs1800896), −597AC (rs1800872)] of the IL-10 5′-flanking region in a hospital-based case–control study of 165 Caucasian patients with cutaneous melanoma from Germany in comparison with 162 healthy cancer-free Caucasian control participants from the same area matched by age. Using multivariate analysis for the number of nevi and skin type, the IL-10 ‘higher producing’ haplotype ITAGC was found to be significantly associated with a reduced risk of developing melanoma (adjusted P=0.02). Although our findings need to be confirmed by independent and larger multicenter studies, we have described for the first time the association of distal gene variants of the IL-10 gene as an independent risk factor for melanoma.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Lens MB, Dawes M . Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma. Br J Dermatol 2004; 150: 179–185.
Baccarelli A, Calista D, Minghetti P, Marinelli B, Albetti B, Tseng T et al. XPD gene polymorphism and host characteristics in the association with cutaneous malignant melanoma risk. Br J Cancer 2004; 90: 497–502.
Shen H, Liu Z, Strom SS, Spitz MR, Lee JE, Gershenwald JE et al. p53 codon 72 Arg homozygotes are associated with an increased risk of cutaneous melanoma. J Invest Dermatol 2003; 121: 1510–1514.
American Cancer Society. Cancer Facts & Figures. American Cancer Society, Inc.: Atlanta, 2008, pp 1–70.
Gilchrest BA, Eller MS, Geller AC, Yaar M . The pathogenesis of melanoma induced by ultraviolet radiation. N Engl J Med 1999; 340: 1341–1348.
IARC. Solar and Ultraviolet Radiation. International Agency for Research on Cancer: Lyon, 1992.
Blankenburg S, Konig IR, Moessner R, Laspe P, Thoms KM, Krueger U et al. Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: a case-control study. Carcinogenesis 2005; 26: 1085–1090.
Mossner R, Anders N, Konig IR, Kruger U, Schmidt D, Berking C et al. Variations of the melanocortin-1 receptor and the glutathione-S transferase T1 and M1 genes in cutaneous malignant melanoma. Arch Dermatol Res 2007; 298: 371–379.
Mossner R, Meyer P, Jankowski F, Konig IR, Kruger U, Kammerer S et al. Variations in the peroxisome proliferator-activated receptor-gamma gene and melanoma risk. Cancer Lett 2007; 246: 218–223.
Kanetsky PA, Holmes R, Walker A, Najarian D, Swoyer J, Guerry D et al. Interaction of glutathione S-transferase M1 and T1 genotypes and malignant melanoma. Cancer Epidemiol Biomarkers Prev 2001; 10: 509–513.
Moore KW, de Waal MR, Coffman RL, O'Garra A . Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683–765.
Mocellin S, Marincola FM, Young HA . Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol 2005; 78: 1043–1051.
Mocellin S, Panelli MC, Wang E, Nagorsen D, Marincola FM . The dual role of IL-10. Trends Immunol 2003; 24: 36–43.
Fortis C, Foppoli M, Gianotti L, Galli L, Citterio G, Consogno G et al. Increased interleukin-10 serum levels in patients with solid tumours. Cancer Lett 1996; 104: 1–5.
Huang S, Ullrich SE, Bar-Eli M . Regulation of tumor growth and metastasis by interleukin-10: the melanoma experience. J Interferon Cytokine Res 1999; 19: 697–703.
Yue FY, Dummer R, Geertsen R, Hofbauer G, Laine E, Manolio S et al. Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules. Int J Cancer 1997; 71: 630–637.
Kube D, Hua TD, von Bonin F, Schoof N, Zeynalova S, Kloss M et al. Effect of interleukin-10 gene polymorphisms on clinical outcome of patients with aggressive non-Hodgkin's lymphoma: an exploratory study. Clin Cancer Res 2008; 14: 3777–3784.
Perrey C, Pravica V, Sinnott PJ, Hutchinson IV . Genotyping for polymorphisms in interferon-gamma, interleukin-10, transforming growth factor-beta 1 and tumour necrosis factor-alpha genes: a technical report. Transpl Immunol 1998; 6: 193–197.
Gibson AW, Edberg JC, Wu J, Westendorp RG, Huizinga TW, Kimberly RP . Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus. J Immunol 2001; 166: 3915–3922.
Mormann M, Rieth H, Hua TD, Assohou C, Roupelieva M, Hu SL et al. Mosaics of gene variations in the Interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used. Genes Immun 2004; 5: 246–255.
Howell WM, Rose-Zerilli MJ . Interleukin-10 polymorphisms, cancer susceptibility and prognosis. Fam Cancer 2006; 5: 143–149.
Martinez-Escribano JA, Moya-Quiles MR, Muro M, Montes-Ares O, Hernandez-Caselles T, Frias JF et al. Interleukin-10, interleukin-6 and interferon-gamma gene polymorphisms in melanoma patients. Melanoma Res 2002; 12: 465–469.
Nikolova PN, Pawelec GP, Mihailova SM, Ivanova MI, Myhailova AP, Baltadjieva DN et al. Association of cytokine gene polymorphisms with malignant melanoma in Caucasian population. Cancer Immunol Immunother 2007; 56: 371–379.
Howell WM, Turner SJ, Bateman AC, Theaker JM . IL-10 promoter polymorphisms influence tumour development in cutaneous malignant melanoma. Genes Immun 2001; 2: 25–31.
Liu D, O'Day SJ, Yang D, Boasberg P, Milford R, Kristedja T et al. Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. Clin Cancer Res 2005; 11: 1237–1246.
Alonso R, Suarez A, Castro P, Lacave AJ, Gutierrez C . Influence of interleukin-10 genetic polymorphism on survival rates in melanoma patients with advanced disease. Melanoma Res 2005; 15: 53–60.
Vuoristo MS . The polymorphisms of interleukin-10 gene influence the prognosis of patients with advanced melanoma. Cancer Genet Cytogenet 2007; 176: 54–57.
von Euw EM, Barrio MM, Furman D, Levy EM, Bianchini M, Peguillet I et al. A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10 -1082 promoter genotype as predictor of disease progression. J Transl Med 2008; 6: 1–14.
Wellek S . Tests for establishing compatibility of an observed genotype distribution with Hardy-Weinberg equilibrium in the case of a biallelic locus. Biometrics 2004; 60: 694–703.
Lake SL, Lyon H, Tantisira K, Silverman EK, Weiss ST, Laird NM et al. Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Hum Hered 2003; 55: 56–65.
Blankenburg S, Konig IR, Moessner R, Laspe P, Thoms KM, Krueger U et al. No association between three xeroderma pigmentosum group C and one group G gene polymorphisms and risk of cutaneous melanoma. Eur J Hum Genet 2005; 13: 253–255.
Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV . An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24: 1–8.
Crawley E, Kay R, Sillibourne J, Patel P, Hutchinson I, Woo P . Polymorphic haplotypes of the interleukin-10 5′ flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum 1999; 42: 1101–1108.
Nagano T, Kunisada M, Yu X, Masaki T, Nishigori C . Involvement of interleukin-10 promoter polymorphisms in nonmelanoma skin cancers-a case study in non-Caucasian skin cancer patients. Photochem Photobiol 2008; 84: 63–66.
Jordan WJ, Eskdale J, Boniotto M, Lennon GP, Peat J, Campbell JD et al. Human IL-19 regulates immunity through auto-induction of IL-19 and production of IL-10. Eur J Immunol 2005; 35: 1576–1582.
Sabat R, Wallace E, Endesfelder S, Wolk K . IL-19 and IL-20: two novel cytokines with importance in inflammatory diseases. Expert Opin Ther Targets 2007; 11: 601–612.
Kreis S, Philippidou D, Margue C, Behrmann I . IL-24: a classic cytokine and/or a potential cure for cancer? J Cell Mol Med 2008; 12: 2505–2510.
Acknowledgements
We are grateful to the Deutsche Forschungsgemeinschaft DFG (Graduate College 1034, www.gcpg.de) for supporting this work and the colleagues of the GRK1034 for helpful discussions.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schoof, N., von Bonin, F., König, I. et al. Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study. Genes Immun 10, 586–590 (2009). https://doi.org/10.1038/gene.2009.40
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/gene.2009.40
Keywords
This article is cited by
-
No association of vitamin D metabolism-related polymorphisms and melanoma risk as well as melanoma prognosis: a case–control study
Archives of Dermatological Research (2012)