|Gene:||IL23R; interleukin 23 receptor|
|Summary:||The protein encoded by this gene is a subunit of the receptor for IL23A/IL23. This protein pairs with the receptor molecule IL12RB1/IL12Rbeta1, and both are required for IL23A signaling. This protein associates constitutively with Janus kinase 2 (JAK2), and also binds to transcription activator STAT3 in a ligand-dependent manner. [provided by RefSeq, Jul 2008]|
|Databases:||OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene|
|Updated:||12 December, 2014|
What does this gene/protein do?
What pathways are this gene/protein implicaed in?
- Cytokine-cytokine receptor interaction
- Jak-STAT signaling pathway
Data from KEGG and BioCarta [BIOCARTA terms] via CGAP
Graph generated 12 December 2014 using data from PubMed using criteria.
Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic. Tag cloud generated 12 December, 2014 using data from PubMed, MeSH and CancerIndex
Scope includes mutations and abnormal protein expression.
Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).
OMIM, Johns Hopkin University
Referenced article focusing on the relationship between phenotype and genotype.
International Cancer Genome Consortium.
Summary of gene and mutations by cancer type from ICGC
Cancer Genome Anatomy Project, NCI
COSMIC, Sanger Institute
Somatic mutation information and related details
Search the Epigenomics database and view relevant gene tracks of samples.
Latest Publications: IL23R (cancer-related)
Recent studies have suggested that Th17 cells may play a role in the pathogenesis of acute myeloid leukemia (AML). This subset of CD4+ cells is characterized by interleukin (IL)-17A and IL-17F production, which share strong homology, and surface expression of the IL-23 receptor (IL-23R). The present study aimed to determine the association between the polymorphic features located within the IL-17A, IL-17F and IL-23R genes and disease susceptibility, progression and response to therapy. In addition, the relationship between the polymorphic variants and the plasma IL-17 levels in patients was analyzed.METHODS:
For this purpose, 187 individuals of Polish origin including 62 AML patients and 125 healthy controls were typed for IL-17A (rs2275913; G-197A), IL-17F (rs763780; A7488G; His161Arg) and IL-23R (rs11209026, G1142A; Arg381Gln) alleles.RESULTS:
The rs763780 IL-17F polymorphism appeared to be associated with susceptibility to the disease. The presence of the minor (G) variant (RR = 4.76, p < 0.001) and its homozygosity (RR = 23.02, p < 0.005) was more frequent among patients than healthy individuals. No significant association was observed for either other polymorphisms studied or IL-17 levels.CONCLUSIONS:
Thus, the rs763780 IL-17F polymorphism was found to be associated with predisposition to AML in the Polish population.Related: Acute Myeloid Leukemia (AML) Polymorphisms
As a key element in the T-helper 17 (Th17) cell-mediated inflammatory process, interleukin-23 receptor (IL-23R) plays a crucial role in the pathogenesis of cancer. Single nucleotide polymorphisms (SNPs) in IL-23R have been frequently studied in several previous case-control cancer studies, but its association with esophageal squamous cell carcinoma (ESCC) in Chinese population has not been investigated. This study examined whether genetic polymorphisms in IL-23R were associated with ESCC susceptibility.METHODS:
A hospital-based case-control study of 684 ESCC patients and 1064 healthy controls was performed to assess the association between four previous reported IL-23R genotypes (rs6682925, rs6683039, rs1884444 and rs10889677) and ESCC risk. The results revealed that the C allele of the rs10889677A>C polymorphism in the 3'UTR of IL-23R gene was inversely associated with the risk of ESCC.RESULTS:
The rs10889677AC genotype had significantly decreased cancer risk (odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.69-1.01) compared to subjects homozygous carriers of rs10889677AA, the risk decreased even further in those carrying rs10889677CC genotype (OR = 0.64, 95% CI = 0.44-0.93). No significant association was found between the other three polymorphisms and the risk of ESCC.CONCLUSION:
These findings indicated that rs10889677A>C polymorphism in IL-23R may play a protective role in mediating the risk of ESCC.Related: Cancer of the Esophagus Esophageal Cancer
Interleukin-23 receptor (IL23R) can interact with IL-23 and, thus, is involved in the T-helper 17 (Th17) cell-mediated inflammatory process as well as tumorigenesis. Recently, a functional single nucleotide polymorphism (SNP) rs10889677 has been identified in the 3'-untranslated region of IL-23R. It has been showed that the rs10889677AC SNP could increase the binding affinity of microRNA let-7f and downregulate IL-23R expression. Several case-control studies have examined the association between this SNP and genetic susceptibility of multiple solid tumors. However, the conclusions are conflicting. Therefore, we conducted this meta-analysis to systematically study the role of this functional IL-23R SNP in development of multiple solid tumors. There are a total of 5 studies are eligible (6731 cases and 7296 healthy controls). Either fixed-effect model or random-effect model was used to calculate pooled odds ratios (ORs) and the 95% confidence interval (95% CI). Significant association between this functional rs10889677 genetic variant and risk of multiple solid tumors were observed (CC genotype vs. AA genotype: OR = 0.59, 95% CI = 0.53-0.66, P < 0.001). These findings demonstrated that the IL-23R rs10889677 genetic variant might play an important part during malignant transformation of multiple solid tumors.Related: Cancer Prevention and Risk Reduction
Yao J, Liu L, Yang MInterleukin-23 receptor genetic variants contribute to susceptibility of multiple cancers.
Gene. 2014; 533(1):21-5 [PubMed
] Related Publications
Interleukin-23 (IL-23) and IL-23 receptor (IL23R) play an important role during the T-helper 17 (Th17) cell-mediated inflammatory process as well as pathogenesis of multiple cancers. Several IL-23R single nucleotide polymorphisms (SNPs), especially rs6682925, rs10889677 and rs1884444 polymorphisms, are considered to have significant impacts on susceptibility of multiple cancers. A number of case-control studies have explored the role these genetic polymorphisms in development of carcinogenesis, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically investigate the associations between the three genetic variants and multiple cancer risk.METHODS:
A total of ten studies are eligible (12,211 patients and 14,650 controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were appropriately calculated using either fixed-effect model or random-effect model.RESULTS:
Significant associations between rs6682925 or rs10889677 polymorphism and cancer risk were found (OR=1.11, 95% CI=1.03-1.21, P=0.007; or OR=0.85, 95% CI=0.71-0.92, P=0.001). However, there was no such association between rs1884444 genotypes and cancer susceptibility (P>0.05).CONCLUSION:
These findings reveal that the IL-23R rs6682925 and rs10889677 genetic variants play a more important part in pathogenesis of multiple cancers.Related: Cancer Prevention and Risk Reduction
Peng Q, Qin Y, Chen Z, et al.Correlation between interleukin‑23 receptor gene polymorphisms and risk of hepatitis B virus infection in patients.
Mol Med Rep. 2013; 8(2):613-20 [PubMed
] Related Publications
There is an increasing amount of evidence supporting the hypothesis that the pathological stage from hepatitis to hepatocellular carcinoma (HCC) is a chronic inflammatory process. Interleukin‑23 (IL‑23) is an important mediator and modulator of inflammation. Specific polymorphisms in the genes encoding subunits of the IL‑23 receptor (IL‑23R) have been consistently observed to be associated with chronic immune‑mediated diseases. In the current study, these variants were hypothesized to affect the risk of hepatitis B virus infection in patients. Three polymorphisms in the IL‑23R gene (rs10889677, rs1884444 and rs11465817) were examined in 84 cases of chronic hepatitis B (HBV), 67 cases of HBV‑related liver cirrhosis, 89 cases of HBV‑related HCC and 94 healthy controls using the polymerase chain reaction (PCR)‑restriction fragment length polymorphism method and DNA sequencing. The results revealed that subjects with the TG genotype of rs1884444 appeared to have higher susceptibility to HCC compared with the TT genotype (adjusted odds ratio (OR), 2.86; 95% confidence interval (CI), 1.39‑5.85; P=0.00). The rs1884444 G allele was associated with a significantly increased risk of HCC compared with the T allele (adjusted OR, 1.58; 95% CI, 0.96‑2.60; P=0.07). The rs11465817 and rs10889677 polymorphisms of the IL‑23R gene were not observed as being relevant to liver disease. These observations indicate that the genetic variants in the IL‑23R gene may contribute to HCC development. Additional studies with larger sample sizes must be conducted to confirm the current observations.Related: Liver Cancer Polymorphisms
To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis.METHODS:
Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p-STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting.RESULTS:
Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:
IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.Related: Colorectal (Bowel) Cancer Signal Transduction
Li J, Zhang L, Zhang J, et al.Interleukin 23 regulates proliferation of lung cancer cells in a concentration-dependent way in association with the interleukin-23 receptor.
Carcinogenesis. 2013; 34(3):658-66 [PubMed
] Related Publications
Research 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 FINDINGS:
We 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 SIGNIFICANCE:
Our 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.Related: Breast Cancer
Carlsson E, Krohn K, Ovaska K, et al.Neuron navigator 3 alterations in nervous system tumors associate with tumor malignancy grade and prognosis.
Genes Chromosomes Cancer. 2013; 52(2):191-201 [PubMed
] Related Publications
Copy number changes or reduced expression of the Neuron navigator 3 (NAV3) gene occurs in neuroblastomas and malignancies of epithelial or lymphoid origin. To elucidate whether NAV3 has a role in the tumorigenesis of nervous system tumors in general, we studied central and peripheral nervous system tumors for NAV3 copy number changes. In search for common tumorigenic denominators, we analyzed 113 central and peripheral nervous system tumors, including glial tumors (grades I-IV gliomas), medulloblastomas, and neuroblastomas. NAV3 copy number changes were studied by fluorescence in situ hybridization and correlated to survival analyses. To identify target genes of NAV3 deletion, NAV3 was silenced by siRNA in glioblastoma cell lines and gene expression profiles were analyzed by Agilent 4×44k dual-color microarrays. Selected upregulations were confirmed by immunohistochemistry and quantitative polymerase chain reaction. We found NAV3 amplifications to dominate in neuronally differentiated tumors, whereas glial tumors showed almost equal proportions of NAV3 deletion and amplification. However, Grade IV gliomas had more frequent NAV3 deletions than grades I-III gliomas. Silencing of NAV3 in glioma cell lines led to the upregulation of receptor genes associated with gonadotropin-releasing hormone and Jak-Stat signaling pathways. Kaplan-Meier analysis of the entire clinical tumor material showed association between NAV3 amplifications and favorable prognosis, as well as NAV3 deletions and unfavorable prognosis. With Cox regression model, a hazard ratio of 0.51 was observed for NAV3 amplifications and 1.36 for NAV3 deletions. We conclude that NAV3 may be a potential new prognostic biomarker and a potential therapeutic target.Related: CGH FISH Childhood Medulloblastoma / PNET Neuroblastoma
Zheng J, Jiang L, Zhang L, et al.Functional genetic variations in the IL-23 receptor gene are associated with risk of breast, lung and nasopharyngeal cancer in Chinese populations.
Carcinogenesis. 2012; 33(12):2409-16 [PubMed
] Related Publications
Xu Y, Liu Y, Pan S, et al.IL-23R polymorphisms, HBV infection, and risk of hepatocellular carcinoma in a high-risk Chinese population.
J Gastroenterol. 2013; 48(1):125-31 [PubMed
] Related Publications
The interleukin-23 receptor (IL-23R) plays an important role in the T-helper 17 cell-mediated inflammatory process and is also involved in tumor immune surveillance, which may be linked to carcinogenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). In this study, we hypothesized that potentially functional genetic variants of the IL-23R gene may modify HCC risk.METHODS:
We genotyped two single-nucleotide polymorphisms (SNPs) of IL-23R, rs6682925 and rs1884444, in a case-control study of 837 HCC cases, 899 HBV surface antigen (HBsAg)-positive controls, and 743 HBsAg-negative controls. A reporter gene assay was performed to evaluate the functional relevance of the rs6682925 SNP located at the promoter region of the IL-23R gene.RESULTS:
We found that the two SNPs were associated with the risk of HCC when compared with both the HBsAg-positive and -negative controls. When compared with all controls, IL-23R rs6682925 and rs1884444 both increased the HCC risk in a recessive genetic model [rs6682925 CC vs. TT/TC: odds ratio (OR) 1.35, 95 % confidence interval (CI) 1.07-1.70; rs1884444 GG vs. TT/TG: OR 1.36, 95 % CI 1.05-1.77]. Furthermore, the variant C allele of rs6682925 in the promoter region of IL-23R was associated with increased reporter gene activity.CONCLUSIONS:
These findings indicate that genetic variants in IL-23R may contribute to HCC development.Related: Liver Cancer
The recently described navigator proteins have a multifaceted role in cytoskeletal dynamics. We report here on the relevance of one of them, navigator 3 (NAV3), in colorectal cancer (CRC).METHODS:
We analysed changes in chromosome 12 and NAV3 copy number in CRC/adenoma samples of 59 patients and in 6 CRC cell lines, using fluorescence in situ hybridisation, loss of heterozygosity, and array-CGH. NAV3 target genes were identified by siRNA depletion, expression arrays, and immunohistochemistry.RESULTS:
NAV3 deletion and chromosome 12 polysomy were detected in 30 and 70% of microsatellite stability (MSS) carcinomas, in 23 and 30% of adenomas and in four of six CRC cell lines. NAV3 amplification was found in 25% of MSS samples. NAV3 alterations correlated with lymph node metastasis. In normal colon cells, NAV3 silencing induced upregulation of interleukin 23 receptor (IL23R) and gonadotropin releasing hormone receptor. In MSS and microsatellite instability tumours, IL23R immunoreactivity correlated with Dukes' staging and lymph node metastases, whereas nuclear beta-catenin correlated with lymph node metastases only.CONCLUSION:
NAV3 copy number changes are frequent in CRC and in adenomas, and upregulation of IL23R, following NAV3 silencing, strongly correlates with Dukes' staging and lymph node metastases. This suggests that NAV3 has a role in linking tissue inflammation to cancer development in the colon.Related: Chromosome 12 Colorectal (Bowel) Cancer FISH
Broen K, van der Waart AB, Greupink-Draaisma A, et al.Polymorphisms in CCR6 are associated with chronic graft-versus-host disease and invasive fungal disease in matched-related hematopoietic stem cell transplantation.
Biol Blood Marrow Transplant. 2011; 17(10):1443-9 [PubMed
] Related Publications
Graft-versus-host disease (GVHD) and fungal infections are frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT). Single nucleotide polymorphisms (SNPs) in genes of the immune system can influence the inflammatory cascade and T cell-driven alloimmune reactions after HSCT, and thus increasing the incidence of GVHD and infectious complications. Here, we investigated the effect of SNPs in IL-23R and CCR6 on posttransplantation outcome in 161 recipients of partially T cell-depleted HSCT. Remarkably, IL-23R SNPs were not associated with clinical outcome, but we found that disparities in the CCR6 tagSNP rs2301436 and SNP rs3093023 are independently associated with the occurrence of chronic GVHD (cGVHD) and invasive fungal disease. In multivariate analysis, patients receiving a transplant from a homozygous rs2301436 G allele donor showed less cGVHD (odds ratio [OR]: 0.16; P = .002), as was the case for a homozygous donor rs3093023 G allele (OR: 0.24; P = .005). In parallel, the GG genotype at rs2301436 in donors was associated with a higher incidence of invasive fungal disease at day 100 after HSCT (OR: 3.59; P = .008). This study shows that CCR6 SNPs can be used to predict clinical outcome, and that polymorphisms in the CCR6 gene may influence T cell-mediated immune reactions after HSCT.Related: Haematological Malignancies & Realted Disorders
Chien MH, Hsin CH, Chou LS, et al.Interleukin-23 receptor polymorphism as a risk factor for oral cancer susceptibility.
Head Neck. 2012; 34(4):551-6 [PubMed
] Related Publications
The purpose of this study was to evaluate the influence of genetic polymorphisms of interleukin (IL)-23 and the IL-23 receptor (IL-23R) on the susceptibility to oral cancer.METHODS:
Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure polymorphisms of these genes in 240 controls and 240 patients with oral cancer.RESULTS:
Individuals with at least 1 varied C allele of rs10889677 (IL-23R polymorphism) had a 1.553-fold risk (95% confidence interval [CI], 1.073-2.241) of developing oral cancer compared with patients with the wild-type A/A homozygote. Patients with oral cancer with at least 1 varied C allele of rs10889677 had a 1.931-fold risk of tumor lymph node metastasis compared with patients with the C/C homozygote.CONCLUSION:
The varied C allele of the IL-23R gene may be considered a factor contributing to increased susceptibility and may be a predictive factor for tumor lymph node metastasis in Taiwanese with oral cancer.Related: Oral Cancer Polymorphisms
Lan F, Zhang L, Wu J, et al.IL-23/IL-23R: potential mediator of intestinal tumor progression from adenomatous polyps to colorectal carcinoma.
Int J Colorectal Dis. 2011; 26(12):1511-8 [PubMed
] Related Publications
Interleukin 23 (IL-23) affects tumor growth by regulating Th cells and plays a vital role in immunosuppression in tumor tissues. However, whether tumor cells are IL-23R positive or whether IL-23 has the potential to influence the growth of cancer cells directly remains unclear. The aim of this study was to clarify the molecular expression patterns of IL-23, IL-23R, and Forkhead box P3 (FOXP3) in normal tissues adjacent to cancer, in intestinal polyps (IP), and in colorectal carcinoma (CRC), and to infer the relationship between the expression patterns of these three molecules and the progress of intestinal tumors from adenomatous polyps to colorectal cancer.METHODS:
The levels of IL-23A, IL-23R, and FOXP3 were evaluated in normal tissues adjacent to cancer (NT, n = 13), IP (n = 26), and CRC (n = 13) using real-time PCR, ELISA, western blotting, immunohistochemistry, and immunocytochemistry.RESULTS:
The expression of IL-23 and FOXP3 increased progressively from NT through to CRC. Immunohistochemistry staining showed that IL-23R was highly positive in carcinoma cells of the CRC group, whereas it was partially positive in cells of other groups. In addition, the human CRC cell line SW-480 exhibited weak IL-23R immunocytochemical positivity.CONCLUSIONS:
We propose that the IL-23/IL-23R pathway is a potential route to facilitate the malignant progression of cancers. The relationship between IL-23 and FOXP3 in the microenvironment of carcinoma led us to deduce that these two molecules may interact with each other. Although the exact mechanism underlying this interaction remains a mystery, we are convinced that these two molecules are relevant in cancer progression and that IL-23 could be a potential target for cancer immunotherapy.Related: Colorectal (Bowel) Cancer FOXP3
Dai J, Hu Z, Dong J, et al.Host immune gene polymorphisms were associated with the prognosis of non-small-cell lung cancer in Chinese.
Int J Cancer. 2012; 130(3):671-6 [PubMed
] Related Publications
Laboratory-based studies showed that host immune genes could influence the prognosis of non-small-cell lung cancer (NSCLC). Therefore, genetic polymorphisms in host immune genes may serve as predictors for NSCLC clinical outcome. To test the hypothesis that functional single nucleotide polymorphisms (SNPs) in host immune genes are associated with the prognosis of NSCLC, we systematically performed a genotyping analysis for a total of 178 SNPs from 52 immune genes in a prospective case cohort of 568 NSCLC patients. Among the 178 SNPs, 24 were significantly associated with NSCLC prognosis in different genetic models and four of them were remained in the final predictive model after multivariate stepwise Cox regression, including IL-5R rs11713419 (5'-untranslated region, 5'-UTR) (P = 0.001), IL23R rs6682925 (5'-flanking region, 5'-FR) (P = 0.017), TLR1 rs5743551 (5'-FR) (P = 0.02) and TLR3 rs3775291 (Leu412Phe) (P = 0.01). We then put the above four SNPs together, and found that the risk of death was significantly increased by 124% (HR = 2.24, 95% CI: 1.33-3.75) for the patients carrying "1" unfavorable locus and by 175% (HR = 2.75, 95% CI: 1.67-4.51) for those carrying "2-4" unfavorable loci. The risk score model and time-dependent ROC analyses further support the four SNPs and clinical risk score model. The area under curve (AUC) at year 5 increased from 0.484 to 0.831 after combining the four SNPs risk score with clinical risk score. These findings indicate that potentially functional polymorphisms in immune genes may serve as prognostic markers of clinical outcome of NSCLC.Related: Non-Small Cell Lung Cancer Lung Cancer
Chronic inflammation is commonly present in gastrointestinal mucosal sites at increased risk for cancer, such as in inflammatory bowel disease (IBD) or chronic gastritis caused by Helicobacter pylori infection. Why some patients have more mucosal inflammation than others, and why certain individuals with chronic inflammation develop cancer, are problems that have not been solved. Unlike the case for the syndromic forms of familial colorectal cancer (CRC), the risks for IBD and other forms of chronic inflammation have not been linked to highly penetrant single gene mutations. Single nucleotide polymorphisms (SNP) are variations in DNA sequence that can be linked to any phenotype (cancer, chronic inflammation, etc.) in genome-wide association studies (GWAS). CRC has been linked to several highly penetrant single gene loci, as well as multiple SNP. The propensity to develop IBD has not been linked to single gene mutations in most instances, but has been linked to SNP in the NOD2 locus (which appear to create hypomorphic alleles for this bacterial response gene), the IL23R locus, the autophagy gene ATG16L1 and a wide range of other loci including the Toll-like receptors, JAK2 and STAT3, and perhaps 70 more. At present, the problem in predicting risk for chronic inflammation is that there are many genetic polymorphisms with relatively modest individual effects. Our challenge is to understand how the SNPs that are linked to variations in the inflammatory response interact with one another (i.e. to understand the 'epistasis' involved), and to integrate this with the variety of individual environmental exposures. This represents an opportunity for informatics science to help personalize our approach to chronic inflammatory diseases of the gut and identify those at greatest risk for cancer.Related: Colorectal (Bowel) Cancer Polymorphisms
Chen B, Zeng Z, Xu L, et al.IL23R +2199A/C polymorphism is associated with decreased risk of certain subtypes of gastric cancer in Chinese: a case-control study.
Cancer Epidemiol. 2011; 35(2):165-9 [PubMed
] Related Publications
Today, the causal relationship between inflammation and gastric cancer is more widely accepted. Genetic variations in inflammation-related genes especially cytokines and their receptors, were thought to partly determine the outcome of Helicobacter pylori (H. pylori) infection and progression of gastric lesions. Interleukin 23 receptor (IL23R), as a key cytokine receptor gene in the important inflammatory IL-17/IL-23 axis, may contribute to gastric cancer predisposition. Up till now, the associations of IL23R gene polymorphisms with subtypes of gastric cancer are largely unknown.AIMS:
We investigated whether the association between IL23R +2199 rs10889677 and gastric cancer risk varies by clinical characteristics and the prognostic value of the polymorphism in a case-control study.METHODS:
A population-based case-control study was conducted in Guangdong. 1010 gastric cancer patients and 800 healthy controls were enrolled. Polymorphism in IL23R was analyzed by PCR-RFLP.RESULTS:
Compared with AA, CC carriers of IL23R +2199 polymorphism were associated with protection against gastric cancer (OR=0.47, 95% CI=0.31-0.71). In stratified analyses, CC genotype was significantly associated with decreased risk of intestinal type (OR=0.44, 95% CI=0.27-0.70), but not with diffuse or mix type of gastric cancer. CC genotype was found to be associated with poorly differentiated (OR=0.43, 95% CI=0.26-0.70), but not with moderately or well differentiated gastric cancer. Multivariate analysis showed IL23R +2199A/C variant was not an independent prognostic factor for gastric cancer patients.CONCLUSION:
IL23R polymorphism influences certain subtypes of gastric cancer according to clinical and pathological features. Understanding the etiologic heterogeneity of gastric cancer may result in improvements in controlling this disorder.Related: Polymorphisms Stomach Cancer Gastric Cancer
Elmaagacli AH, Steckel N, Ditschkowski M, et al.Toll-like receptor 9, NOD2 and IL23R gene polymorphisms influenced outcome in AML patients transplanted from HLA-identical sibling donors.
Bone Marrow Transplant. 2011; 46(5):702-8 [PubMed
] Related Publications
We evaluated the influence of gene polymorphisms of TLR9 (T1237C; T1486C), IL23R (A1142G), and NOD2 SNP8 (R702W), SNP12 (G908R) and SNP13 (1007fs) on outcome of hematopoietic SCT in a homogenous group of 142 AML patients after non-T-cell-depleted myeloablative transplantation from HLA-identical sibling donors. In our retrospective study, we found that TLR9 gene variant at 1486 influenced transplant outcome. Estimated 5-year OS in patients with the CC gene variant of TLR9 was 70.2% compared with 44.8% (P<0.027) in patients with TC/TT of TLR9 gene. No significant influences on 5-year OS were found for gene polymorphisms of NOD2 or IL23R (A1142G) in this study group. The 5-year treatment-related mortality was lowest in patients with CC gene variant of TLR9 (7.8 vs 23.1%; NS). Acute GVHD grade III-IV was higher in patients with NOD2 gene variants (28 vs 12.8%; P=0.065). In contrast, patients transplanted from donors with the gene variant of IL23R had no occurrence of severe acute GVHD grade III-IV (0 vs 18.4%; P<0.048). However, multivariate analysis confirmed the influence of NOD2 gene variants on the occurrence of acute GVHD grade II-IV after transplant. These results suggest that the gene variants of TLR9, NOD2 and Il23R had influence on the outcome of transplant.Related: Acute Myeloid Leukemia (AML) Polymorphisms
Chen J, Lu Y, Zhang H, et al.A nonsynonymous polymorphism in IL23R gene is associated with risk of gastric cancer in a Chinese population.
Mol Carcinog. 2010; 49(10):862-8 [PubMed
] Related Publications
Interleukin-23 receptor (IL-23R) is a key element in T helper (Th)17 cell-mediated inflammatory process, which plays an important role in pathogenesis of gastric cancer. Genetic variants of IL-23R have been identified as the predisposing factors for immunopathologic process. In this study, we hypothesized that the functional genetic variants of IL-23R gene may modify the risk of gastric cancer. To test this hypothesis, we conducted a case-control study including 1043 gastric cancer patients and 1089 controls in a Chinese population to assess the association between two potentially functional single nucleotide polymorphisms (SNPs) rs6682925 T>C and rs1884444 T>G of IL-23R and risk of gastric cancer. We found that the variant allele (G) of rs1884444 T>G, with amino acid His substituted by Gln at codon 3, was significantly associated with a decreased risk of gastric cancer [adjusted allelic odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.68-0.88]. In the stratified analysis, we found that this protective effect of rs1884444 G allele was mainly evident in intestinal-type gastric cancer (adjusted allelic OR = 0.75, 95% CI = 0.65-0.87) other than in diffuse-type gastric cancer (adjusted allelic OR = 0.96, 95% CI = 0.76-1.22). However, we did not find any significant association of rs6682925 T>C with gastric cancer risk. These findings indicate, for the first time, that the nonsynonymous variant rs1884444 T>G of IL-23R may contribute to gastric cancer susceptibility, especially in intestinal-type gastric cancer, in Chinese population.Related: Stomach Cancer Gastric Cancer
Nguyen Y, Al-Lehibi A, Gorbe E, et al.Insufficient evidence for association of NOD2/CARD15 or other inflammatory bowel disease-associated markers on GVHD incidence or other adverse outcomes in T-replete, unrelated donor transplantation.
Blood. 2010; 115(17):3625-31 [PubMed
] Free Access to Full Article Related Publications
Previous European studies suggest NOD2/CARD15 and interleukin-23 receptor (IL-23R) donor or recipient variants are associated with adverse clinical outcomes in allogeneic hematopoietic stem cell transplantation. We reexamined these findings as well as the role of another inflammatory bowel disease (IBD) susceptibility gene (immunity-related GTPase family, M [IRGM]) on transplantation outcomes in 390 US patients and their matched unrelated donors, accrued between 1995 and 2004. Patients received T-replete grafts with mostly myeloablative conditioning regimens. Multivariate analyses were performed for overall survival, disease-free survival, transplantation-related mortality, relapse, and acute and chronic graft-versus-host disease. Of 390 pairs, NOD2/CARD15 variant single nucleotide polymorphisms (SNPs) were found in 14% of donors and 17% of recipients. In 3% both donor and recipient had a mutant SNP. Thirteen percent of donors and 16% of recipients had variant IL23R SNPs, with 3% having both donor and recipient variants. Twenty-three percent of both donors and recipients had variant IRGM SNPs. None of the 3 IBD-associated alleles showed a statistically significant association with any adverse clinical outcomes. Our results do not support an association between the 3 IBD-associated SNPs and adverse outcomes after matched unrelated donor hematopoietic cell transplantations in US patients.Related: Haematological Malignancies & Realted Disorders USA
Zhang Z, Zhou B, Zhang J, et al.Association of interleukin-23 receptor gene polymorphisms with risk of ovarian cancer.
Cancer Genet Cytogenet. 2010; 196(2):146-52 [PubMed
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Among gynecological malignancies, ovarian cancer is the leading cause of death. The overall 5-year survival rate remains poor, and the pathogenesis is unknown. The interleukin-23 receptor (IL23R) is known to be critically involved in the carcinogenesis of different malignant tumors. To assess the role of IL23R in ovarian cancer, we conducted a study to investigate the polymorphisms of the IL23R gene in 96 Han Chinese women with histologically proven ovarian cancer. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. In all three single nucleotide polymorphisms of IL23R studied, the distribution of genotype and allele frequencies of rs10889677 differed significantly between patients and controls. The frequency of allele C of rs10889677 was significantly increased in cases compared with controls (0.281 vs. 0.183, odds ratio OR=1.752, 95% confidence interval CI=1.107-2.772). Furthermore, when stratified by tumor stage, we found that the allele frequencies of rs11465817 differed significantly between FIGO stage I+II and III+IV. The higher frequency of allele A was significantly associated with advanced ovarian cancer (P=0.027, OR=2.087, 95% CI=1.083-4.023). These findings indicate that IL23R polymorphisms may play an important role in the susceptibility and prognosis of ovarian cancer in the Chinese population.Related: Ovarian Cancer
Büning C, Schmidt HH, Molnar T, et al.Heterozygosity for IL23R p.Arg381Gln confers a protective effect not only against Crohn's disease but also ulcerative colitis.
Aliment Pharmacol Ther. 2007; 26(7):1025-33 [PubMed
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BACKGROUND: A recent study reported that a non-synonymous single nucleotide polymorphism (rs11209026, p.Arg381Gln) located in the IL23R gene is a protective marker for inflammatory bowel disease.
AIM: To analyse the frequency of p.Arg381Gln in three independent European inflammatory bowel disease cohorts and to evaluate how this variant influences disease behaviour.
METHODS: We assessed a European cohort of 919 inflammatory bowel disease patients and compared the IL23R p.Arg381Gln genotype frequency with 845 healthy controls. Inflammatory bowel disease patients originated from Germany [Crohn's disease (CD): n = 318; ulcerative colitis (UC): n = 178], Hungary (CD: n = 148; UC: n = 118) and the Netherlands (CD: n = 157). Ethnically matched controls were included. We performed subtyping analysis in respect to CARD15 alterations and clinical characteristics.
RESULTS: The frequency of the glutamine allele of p.Arg381Gln was significantly lower in inflammatory bowel disease patients compared with controls in a pooled analysis of all three cohorts (P < 0.000001) as well as in the individual cohorts (Germany: P = 0.001, Hungary: P = 0.02 and the Netherlands: P = 0.0002). The p.Arg381Gln genotype distribution was similar between CD and UC. We did not observe either statistical interactions between p.Arg381Gln and CARD15 variants or any significant associations between p.Arg381Gln genotype and subphenotypes.
CONCLUSIONS: The p.Arg381Gln IL23R variant confers a protective effect against both CD and UC, but does not determine disease phenotype.