Association of IL4 , IL13 , and IL4R polymorphisms with gastrointestinal cancer risk: A meta-analysis

Cho, Young Ae; Kim, Jeongseon

doi:10.1016/j.je.2016.06.002

Cited by 27 publications

(14 citation statements)

References 41 publications

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“…We found that IL-4 rs2070874 T>C polymorphism seemed to be a protective factor for ESCC development. Our findings were similar to a previous meta-analysis that suggested that the IL-4 rs2070874 C allele could be associated with a decreased susceptibility of gastrointestinal cancer [ 14 ]. A functional study indicated that the IL-4 rs2070874 allele C could promote a higher level of IL-4 in plasma [ 49 ].…”

Section: Discussionsupporting

confidence: 92%

Investigation ofIL-4, IL-10, andHVEMpolymorphisms with esophageal squamous cell carcinoma: a case–control study involving 1929 participants

et al. 2020

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It is believed that an individual’s hereditary factors may be involved in the development of esophageal cancer (EC). The present study recruited 721 esophageal squamous cell carcinoma (ESCC) cases and 1,208 controls and explored the roles of single nucleotide polymorphisms (SNPs) in the interleukin-4 (IL-4), Il-10, and herpesvirus entry mediator (HVEM) genes in contributing to ESCC risk. IL-4, Il-10, and HVEM SNPs were analyzed by employing a SNPscan method. After adjustment for BMI, smoking, drinking, age and gender, we identified that the rs2070874 T>C locus in IL-4 gene decreased the risk of ESCC (CC vs. TT: P=0.008; CC vs. TT/TC: P=0.010). After a stratified analysis, we suggested that the IL-4 rs2070874 T>C variants might be a protective factor for ESCC in in male, ≥63 years old, never smoking, drinking and BMI2 subgroups. In addition, we identified that the rs2243263 G>C polymorphism in IL-4 gene was a risk factor for ESCC development in the BMI≥24 kg/m2 subgroup (GC vs. GG: P=0.030 and GC/CC vs. GG: P=0.018). We identified an association of the IL-4 rs2070874 T>C SNP with the decreased susceptibility of ESCC in stage I/II subgroup. Finally, we found an association of the IL-10 rs1800872 T>G SNP with a worse differentiation (TG vs. TT: P=0.048 and GG/TG vs. TT: P=0.032). In conclusion, the findings indicate a potential importance of IL-4 rs2070874 T>C, IL-4 rs2243263 G>C and IL-10 rs1800872 T>G SNPs in the development of ESCC.

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Section: Discussionsupporting

confidence: 92%

Investigation ofIL-4, IL-10, andHVEMpolymorphisms with esophageal squamous cell carcinoma: a case–control study involving 1929 participants

et al. 2020

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“…IL4 is also involved in radiation-induced aggressive tumor behavior in human cancer cells [ 30 ]. Clinical-based studies suggest that polymorphisms of IL4 and IL4R can affect susceptibility to gastrointestinal cancer [ 31 ]. Moreover, IL4 promotes M2 macrophage activation, which further induces cancer metastasis [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

PKN2 in colon cancer cells inhibits M2 phenotype polarization of tumor-associated macrophages via regulating DUSP6-Erk1/2 pathway

et al. 2018

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BackgroundProtein kinase N2 (PKN2) is a PKC-related serine/threonine-protein kinase. PKN2 is required for tumor cell migration, invasion and apoptosis. However, the functional role of PKN2 in regulating tumor associated macrophages (TAMs) polarization in colon cancer has never been reported.MethodsPKN2 expression in human colon cancer tissues was examined with immunohistochemistry (IHC). M1/M2 macrophage signatures were evaluated by RT-PCR, IHC and flow cytometry. The effects of PKN2 on tumor growth and TAM polarization were investigated both in vitro and in vivo. PKN2 targeted cytokines/pathway were analyzed by gene expression analysis and further confirmed by PCR, luciferase assay or western blot. Correlations between PKN2 and transcriptional factors for IL4 and IL10 were confirmed by ChIP-qPCR. The catalytic activities of PKN2 and DUSP6 were determined by kinase activity assay. Interactions between PKN2 and DUSP6 were confirmed by Co-IP.ResultsThe expression of PKN2 in colon cancer cells predicted a favorable prognosis and was associated with low M2 macrophage content in human colon cancer tissues. PKN2 inhibited tumor growth in mice xenograft model and inhibited M2 phenotype polarization both in vitro and in vivo. Mechanistically, PKN2 suppresses the expression of IL4 and IL10 from colon cancer cells by inhibiting Erk1/2 phosphorylation, which is required for phosphorylation and binding of CREB and Elk-1 to the promoters of IL4 and IL10. DUSP6, which is phosphorylated and activated through direct association with PKN2, suppresses Erk1/2 activation.ConclusionsThe expression of PKN2 in colon cancer cells suppresses tumor associated M2 macrophage polarization and tumor growth. Targeting PKN2 signaling pathway may provide a potential therapeutic strategy for colon cancer.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0747-z) contains supplementary material, which is available to authorized users.

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“…There are several previous meta-analyses also concerned about IL-4R and tumorigenesis. Cho et al 50 demonstrated a reduced risk of GC for rs1801275, but they mixed the gastric cancer, esophageal cancer, pancreatic cancer and colorectal cancer, without any subgroup analysis of cancer type. Wang et al 51 performed a meta-analysis about IL-4R and cancer risk on rs1801275, rs1805010 and rs1805015, however, they only enrolled 36 studies, and didn't adjust the P value of Q-test, which might lead to statistical error.…”

Section: Discussionmentioning

confidence: 99%

Genetic Association between Interleukin-4 Receptor Polymorphisms and Cancer Susceptibility: A Meta-Analysis Based on 53 Case-Control Studies

Zeng

Fan

et al. 2019

J. Cancer

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Polymorphisms in interleukin-4 receptor (IL-4R) gene have been reported susceptible to a variety of cancer types, nevertheless, data from these publications remained inconsistent and controversial. We further performed a comprehensive meta-analysis to present a precise estimation of its relationship. Extensive retrieve was performed in PubMed, Google Scholar and Web of Science up to May 25, 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were conducted to evaluate the overall strength of the associations in five genetic models, as well as in subgroup analyses, stratified by ethnicity, cancer type or source of control. Q-test, Egger's test and Begg's funnel plot were applied to evaluate the heterogeneity and publication bias. In-silico analysis was managed to demonstrate the relationship of IL-4R expression correlated with cancer tissues. Finally, 31 publications including 53 case-control studies were enrolled, with 24,452 cases and 24,971 controls. After a comprehensive analysis, no significant evidence was revealed for the association between four IL-4R polymorphisms (rs1801275, rs1805010, rs1805015, rs2057768) and cancer susceptibility in the overall population, as well as the subgroup analysis stratified by ethnicity, cancer type, the genotyping method or the source of control. To sum up, no evidence was identified between IL-4R polymorphisms and overall cancer susceptibility. Further well-designed studies with large sample sizes will be continued on this issue of interest.

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Association of IL4 , IL13 , and IL4R polymorphisms with gastrointestinal cancer risk: A meta-analysis

Cited by 27 publications

References 41 publications

Investigation ofIL-4, IL-10, andHVEMpolymorphisms with esophageal squamous cell carcinoma: a case–control study involving 1929 participants

Investigation ofIL-4, IL-10, andHVEMpolymorphisms with esophageal squamous cell carcinoma: a case–control study involving 1929 participants

PKN2 in colon cancer cells inhibits M2 phenotype polarization of tumor-associated macrophages via regulating DUSP6-Erk1/2 pathway

Genetic Association between Interleukin-4 Receptor Polymorphisms and Cancer Susceptibility: A Meta-Analysis Based on 53 Case-Control Studies

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