Abstract
Interleukin-4 receptor (IL-4R) gene single nucleotide polymorphisms (SNPs) are implicated in cancer development. However, results from the published reports have remained inconclusive. The objective of this study was to conduct a meta-analysis investigating the association between polymorphisms in IL-4R gene and cancer risk. Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) were searched for case- control studies published up to October 30, 2012 that investigated IL-4R polymorphisms and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of any associations. Three IL-4R polymorphisms (Q576R, rs1801275; I75V, rs1805010; S503P, rs1805015) in 21 case-control studies were analyzed. Our meta-analysis indicated that these three polymorphisms are not associated with cancer risk when all studies were pooled together. In the subgroup analysis by tumor site, the results showed that Q576R G allele carriers were associated with a significantly decreased cervical cancer risk (recessive model: OR = 0.77, 95%CI = 0.60-0.98; homozygote comparison: OR = 0.76, 95%CI = 0.58-0.98). I75V G allele carriers were associated with a decreased risk of renal cancer (dominant model = 0.71, 95%CI = 0.57-0.89, heterozygote comparison: OR = 0.69, 95%CI = 0.55-0.87). When stratified by ethnicity, Q576R G allele carriers were associated with a decreased cancer risk in Caucasians (dominant model: OR = 0.90, 95%CI = 0.83-0.98; heterozygote comparison: OR = 0.89, 95%CI = 0.82-0.98). I75V G allele carriers were associated with a decreased cancer risk in Asians (heterozygote comparison: OR = 0.76, 95%CI = 0.62-0.94). S503P C allele carriers were also associated with a decreased cancer risk in Asians (CC VS TT: OR = 0.29, 95%CI = 0.08-0.99). Our results suggest that Q576R, I75V and S503P may be associated with a decreased cancer risk for certain types of cancers and in some specific ethnic groups. Future case-control studies with large sample size are needed to evaluate these associations in detail.
Highlights
Cancer is a multifactorial disease which has a strong genetic predisposition (Hamajima et al, 2001; Engle et al, 2006)
Our results suggest that Q576R, I75V and S503P may be associated with a decreased cancer risk for certain types of cancers and in some specific ethnic groups
Two studies were subjected to the mixed group for Statistical Analysis Odds ratios (ORs) [odds ratio] and 95% confidence intervals (CIs) were used to estimate the strength of association between the Interleukin-4 receptor (IL-4R) polymorphisms
Summary
Cancer is a multifactorial disease which has a strong genetic predisposition (Hamajima et al, 2001; Engle et al, 2006). The etiology of cancer hasn’t been totally illuminated (Hanahan et al, 2000), evidence shows that the development of cancer depends on immune conditions (de Visser et al, 2006). It has been estimated that cancer is preceded by chronic inflammation in up to a third of all case (Ames et al, 1995), in which cytokines play a crucial role such as tumor necrosis factor alpha, IL-10 and IL-4 (Sheu et al, 2008; Ali et al, 2012; Sim et al, 2012). There is evidence to suggest that Il-4R may be associated with carcinogenesis progress. IL-4 level was higher in higher-stage tumor tissues compare with tissues from lower-stage patient (Onishi et al, 1999). IL-4 can inhibit the differentiation of Th1 lymphocytes and down-regulate the immune response of immune cells against malignant cells, promote tumor cells escape from immune surveillance (Grivennikov et al, 2010)
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