Interleukin and interleukin receptor gene polymorphisms and susceptibility to melanoma

Department of aEpidemiology, Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Melanoma research (Impact Factor: 2.28). 11/2008; 18(5):330-5. DOI: 10.1097/CMR.0b013e32830658b2
Source: PubMed


Genetic variation in immune-regulating components such as cytokines may lead to interindividual differences in immunosuppression response and susceptibility to melanoma. We evaluated the associations between genetic variants in five interleukins (IL) and IL receptor genes (IL-4, IL-4R, IL-6, IL-6R, and IL-10) and the risk of melanoma. Twenty-five single nucleotide polymorphisms (SNPs) were selected that are functionally relevant or tagging SNPs of each gene. We conducted a nested case-control study of 219 female patients and 219 matched controls within the Nurses' Health Study. We observed that in the IL-6R gene, four SNPs in linkage disequilibrium were associated with an increased risk of melanoma. Three are located in introns (rs6684439, rs4845618, and rs4845622), and one is a nonsynonymous SNP in exon 9 [rs8192284 (Asp358Ala)]. An elevated risk of melanoma was observed in the heterozygous groups of these SNPs with odds ratio of 1.74 [(95% confidence interval, 1.07, 2.81) for rs6684439, 1.72 (1.04, 2.84) for rs4845618, 1.69 (1.03, 2.75) for rs4845622, and 1.68 (1.04, 2.73) for rs8192284]. But these associations were not observed in the homozygous variant group with odds ratios ranging from 0.93 to 1.03. We did not find significant results for the SNPs in the other four genes. These data suggest the involvement of IL-6R in melanoma development. Further studies are needed to confirm these findings.

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    • "Specifically, IL-6R +48892 AA genotype significantly increased CCA risk but not advanced periductal fibrosis (unpublished). As a surrogate susceptibility gene, several studies suggested that this polymorphic variant is associated with many diseases including metabolic syndromes (Esteve et al., 2006; Jiang et al., 2010), inflammatory diseases (Lamas et al., 2010; Marinou et al., 2010) as well as malignancy (Gu et al., 2008). All these reports speculate a high risk is associated with the lower allele frequency of allele C or the higher allele frequency of allele A. Similarly, our results showed that the allele C carrier reduced risk of CCA (OR=0.27; "
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    • "In IL-6 polymorphisms, females with the CC genotype of IL-6 -174 G/C have an earlier onset of type 1 diabetes when compared with IL-6 -174G allele females and all males [24]. Of studies focused on IL-6R polymorphisms, some have analyzed females (in relation to IL-6 levels, CRP levels, bone mineral density, obesity, hyperandrogenism, preterm birth, type 2 diabetes, and melanoma) [25-32], and another concentrated on males (studying the relationship between IL-6R polymorphisms and obesity) [33]. Most analyses of IL-6R SNPs have not investigated (or at least have not reported) gender differences. "
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