Association of IL‐1 polymorphisms and IL‐1 serum levels with susceptibility to nasopharyngeal carcinoma
ABSTRACT Previous studies demonstrated that the polymorphism of interleukin-1 (IL-1) produce alterations of the protein expression and may contribute to oncogenetic processes. The aim of this study was to investigate the relationship between IL-1A gene polymorphisms and NPC susceptibility and the influence of on IL-1α serum levels in cases versus controls. To test whether the genetic variants of IL-1A gene modify the risk of nasopharyngeal carcinoma (NPC), we compared the −889C/T and rs3783553 polymorphisms between 248 patients with NPC and 296 healthy controls using polymerase chain reaction–restriction fragment length polymorphism. Serum IL-1α levels were measured by enzyme-linked immunosorbent assay. The rs3783553 (TTCA insertion or deletion) polymorphism of the IL-1A gene was significantly associated with the susceptibility to NPC. The variant homozygote genotype +/+ was associated with a significantly reduced risk of NPC as compared with the wild homozygote −/− genotype, and the serum IL-1α levels were significantly lower in individuals with homozygous +/+ genotypes. No association was found between the −889C/T polymorphisms and risk of NPC, and no statistically significant differences were found between rs3783553 polymorphism and clinical pathology indices. The IL-1A rs3783553 polymorphism might contribute to a risk of developing NPC by affecting the serum IL-1α secretion in the Chinese population. Mol. Carcinog. © 2010 Wiley-Liss, Inc.
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ABSTRACT: Acute splenic sequestration (ASS) and chronic hypersplenism are common features of homozygous sickle cell (SS) disease in the first 5 years of life affecting one-third of subjects in the Jamaican Cohort Study. The risk factors are largely unknown and the current study explores a possible role of genetic factors. We have explored these in subjects who received splenectomy in the management of ASS (n=8) or chronic hypersplenism (n=9) along with age, gender, and genotype matched controls using Luminex Technology to assess 42 human cytokines/chemokines, including IL-1α and CXCL10 (IP-10). Levels of IL-1α (p=0.008) and CXCL10 (p=0.009) were significantly elevated in patients treated by splenectomy compared with the control group. Levels of IL-1α were significantly higher in those with a history of ASS compared with matched normal controls (p=0.028) but not in those treated for hypersplenism (p=0.093). Furthermore, several significant differences were found in the median ratios of some cytokine biomarkers between the splenectomized group and the normal controls. These observations are consistent with acute splenic sequestration having a distinct phenotype which may be helpful in predicting those at risk of this complication and suggest that the mechanism of these differences merit further study.Disease markers 01/2012; 32(5):295-300. · 2.14 Impact Factor
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ABSTRACT: While infection with Epstein-Barr virus (EBV) is known to be an essential risk factor for the development of nasopharyngeal carcinoma (NPC), other co-factors including genetic factors are thought to play an important role. In this review, we summarize association studies conducted over the past decade to evaluate the role of genetic polymorphisms in NPC development. A review of the literature identified close to 100 studies, including 3 genome-wide association studies (GWAS), since 2000 that evaluated genetic polymorphisms and NPC risk in at least 100 NPC cases and 100 controls. Consistent evidence for associations were reported for a handful of genes, including immune-related HLA Class I genes, DNA repair gene RAD51L1, cell cycle control genes MDM2 and TP53, and cell adhesion/migration gene MMP2. However, for most of the genes evaluated, there was no effort to replicate findings and studies were largely modest in size, typically consisting of no more than a few hundred cases and controls. The small size of most studies, and the lack of attempts at replication have limited progress in understanding the genetics of NPC. Moving forward, if we are to advance our understanding of genetic factors involved in the development of NPC, and of the impact of gene-gene and gene-environment interations in the development of this disease, consortial efforts that pool across multiple, well-designed and coordinated efforts will most likely be required.Seminars in Cancer Biology 04/2012; 22(2):107-16. · 7.44 Impact Factor