A miRNA Binding Site Single-Nucleotide Polymorphism in the 3′-UTR Region of the IL23R Gene Is Associated with Breast Cancer

Abstract

BackgroundResearch into the etiology of breast cancer has recently focused on the role of the immunity and inflammation. Interleukin-23 and its receptor (IL23R) guide T cells towards the Th17 phenotype. IL23R single nucleotide polymorphisms (SNPs) have been shown to be associated with digestive system cancers. To evaluate the influences of IL23R gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in Chinese Han women.Methodology and Principal FindingsWe genotyped two tag SNPs (rs10889677 in the 3′-UTR region and nonsynonymous variants rs1884444 in exon 2) in IL23R gene of 491 breast cancer patients and 502 matched healthy controls. The genotypes were determined using the SNaPshot technique. The differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed with the Chi-square test for trends. For rs10889677 in IL23R, the frequencies of the AA genotype and the A allele were statistical significant higher in breast cancer patients than in controls (P = 0.0084 and P = 0.0171, respectively), whereas the C allele was associated with an earlier age of breast cancer onset (50.6 years for AA, 48.7 years for AC and 46.0 years for CC (P = 0.0114)) in case-only study. The clinical features analysis demonstrated significant associations between rs1884444 in IL23R and human epidermal growth factor receptor 2 (Her-2) and tumor size status.Conclusions and SignificanceOur results suggest that a miRNA binding site SNP in the 3′-UTR region of the IL23R gene may be associated with the risk of breast cancer and contribute to the early development of breast cancer in Chinese women.

Genetic polymorphisms in miRNAs targeting the estrogen receptor and their effect on breast cancer risk

“…Previous work by our laboratory and others has shown that SNPs in micro-RNAs and their binding sites on genes have influence on breast cancer risk ( Kontorovich et al, 2010 , Pastrello et al, 2010 , Smith et al, 2012 ; Wang et al, 2012; Zhang et al, 2011 , Zheng et al, 2011 ). This includes both sporadic and familial forms, where polymorphisms in miRNAs have been found to alter the age of onset of tumors ( Pastrello et al, 2010 ).…”

Differential Expression of MicroRNAs in Breast Cancers from Four Different Ethnicities

“…Numerous studies are beginning to elucidate their potential as diagnostic, prognostic, and predictive biomarkers [9, 10]. Evidence is building to show that polymorphisms in some miRs are associated with breast cancer susceptibility [11]. More recently, elevated plasma levels of miR-21 and miR-146a were identified in women with breast cancer [12].…”

Bioinformatic Prediction of SNPs within miRNA Binding Sites of Inflammatory Genes Associated with Gastric Cancer

“…Variants in 3'UTR of some genes were reported to have relation with higher susceptibility to certain type of cancers (Lheureux et al, 2011;Wang et al, 2012;Iuliano et al, 2013;Skeeles et al, 2013). SNPs within the miRNA binding sites have been shown to affect the ability of miRNAs and target genes binding, resulting in abnormal mRNA and protein expression (Kertesz et al, 2007;Wang et al, 2008;Skeeles et al, 2013), which will influence the susceptibility risk of certain cancers.…”