ArticleCarcinogenesis2013
Reduced type II interleukin-4 receptor signalling drives initiation, but not progression, of colorectal carcinogenesis: evidence from transgenic mouse models and human case-control epidemiological observations.
Article in Carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Potential Risks Related to Modulating Interleukin-13 and Interleukin-4 Signalling: A Systematic Review.Drug safety · 2018Pooled it
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- Managing Atopic Dermatitis with Dupilumab in Special Populations: A Case Series Study.Clinical, cosmetic and investigational dermatology · 2025Article
- The dichotomy of regulatory B cells in cancer versus allergic disease.Molecular carcinogenesis · 2024Review
- Asthma is associated with a lower incidence of metastatic colorectal cancer in a US patient cohort.Frontiers in oncology · 2023Article
- Recruitment of M1 Macrophages May Not Be Critical for Protection against Colitis-Associated Tumorigenesis.International journal of molecular sciences · 2021Article
- The Impact of Monoclonal Antibodies on Airway Smooth Muscle Contractility in Asthma: A Systematic Review.Biomedicines · 2021Review
- Possible Roles of Interleukin-4 and -13 and Their Receptors in Gastric and Colon Cancer.International journal of molecular sciences · 2021Review
- Review
- Expression of IL4Rα and IL13Rα1 are associated with poor prognosis of soft-tissue sarcoma of the extremities, superficial trunk, and retroperitoneum.Diagnostic pathology · 2021Article
- Increased Th17-Related Cytokine Serum Levels in Patients With Multiple Polyps of Unexplained Origin.Clinical and translational gastroenterology · 2020Observational
- Article
- Genetic Association between Interleukin-4 Receptor Polymorphisms and Cancer Susceptibility: A Meta-Analysis Based on 53 Case-Control Studies.Journal of Cancer · 2019Article
- Profiles of alternative splicing in colorectal cancer and their clinical significance: A study based on large-scale sequencing data.EBioMedicine · 2018Article
- Cytokine-Induced Modulation of Colorectal Cancer.Frontiers in oncology · 2016Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
We investigated the role of interleukin (IL)-4 receptor (IL-4R) signalling during mouse carcinogen-induced colorectal carcinogenesis and in a case-control genetic epidemiological study of IL-4Rα single nucleotide polymorphisms (SNPs). Azoxymethane-induced aberrant crypt focus (ACF; 6 weeks) and tumours (32 weeks) were analysed in wild-type (WT) BALB/c mice, as well as in IL-4Rα (-) (/-) , IL-13 (-/-) and 'double-knockout' (DKO) animals. Colorectal cancer (CRC) cases (1502) and controls (584) were genotyped for six coding IL-4Rα SNPs. The association with CRC risk and CRC-specific mortality was analysed by logistic regression. Lack of IL-4Rα expression was associated with increased ACFs [median 8.5 ACFs per mouse (IL-4Rα (-/-) ) versus 3 (WT); P = 0.007], but no difference in the number of colorectal tumours [mean 1.4 per mouse (IL-4Rα (-/-) ) versus 2 (WT)], which were smaller and demonstrated reduced nuclear/cytoplasmic β-catenin translocation compared with WT tumours. Tumour-bearing IL-4Rα (-/-) mice had fewer CD11b(+)/Gr1(+) myeloid-derived suppressor splenocytes than WT animals. IL-13 (-/-) mice developed a similar number of ACFs to IL-4Rα (-/-) and DKO mice. There was a significant increase in CRC risk associated with the functional SNP Q576R [odds ratio 1.54 (95% confidence interval 0.94-2.54), P trend 0.03 for the minor G allele]. There was no effect of IL-4Rα genotype on either CRC-specific or all-cause mortality. These combined pre-clinical and human data together demonstrate that reduced IL-4R signalling has stage-specific effects on colorectal carcinogenesis (increased CRC initiation and risk but reduced tumour progression and no effect on CRC mortality). These results should prompt evaluation of the effect of pharmacological manipulation of IL-4R signalling on future CRC risk and for CRC treatment.
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