The IL-23/IL-17 axis may be important in obesity-associated cancer by way of the activation of multiple signal pathways

Chen, Jiezhong

doi:10.1038/ijo.2010.29

Cited by 9 publications

(13 citation statements)

References 9 publications

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“…Adipose tissue is now recognized as an immune organ that secretes numerous immunomodulatory factors (cytokines) and seems to be a significant source of inflammatory signals known to cause insulin resistance (58). Therefore, obese patients have the systemic inflammatory responses, which are associated with increases in serum levels of C reactive protein (CRP) and different cytokines including several interleukins (IL-6, IL-8 and IL-11) and TNF-α (59)(60)(61)(62)(63). CRP is the most recognized biologic marker of chronic systematic inflammation, and it is conceivable that the CRP gene may work together with obesity in the development of endometrial cancer (64).…”

Section: Mechanisms Of Obesity-associated Endometrial Cancermentioning

confidence: 99%

Obesity-associated endometrial and cervical cancers

Chen²,

Zhao³

2013

Front Biosci

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Epidemiological studies have indicated that obesity (body mass index-BMI>30) and overweight (BMI>25) directly associated with risk of many cancers. The association of obesity with cancer risks may be explained by the alterations in the metabolism of endogenous hormones, production of specific proteins and cytokines, adipose related inflammatory reactions, and genetic factors. This review aims to illustrate the link between obesity and occurrence and prognosis of endometrial and cervical cancers. Convincing scientific evidence shows that nutrition and lifestyle factors initiate the development of obesity with excessive adipose tissues, which trigger production of hormones, cytokines and other factors to promote growth of cancer cells. Obese women with either endometrial or cervical cancer, especially in postmenopausal period, have shown a significantly higher mortality. This is mainly due to that the obese women are more vulnerable in cancer occurrence and they are more likely to miss routine cancer screening, putting them at a greater risk for delayed diagnosis of these cancers and deteriorate prognosis. Thus, healthcare providers should pay particular attention to this more vulnerable group of women.

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Section: Mechanisms Of Obesity-associated Endometrial Cancermentioning

confidence: 99%

Obesity-associated endometrial and cervical cancers

Chen²,

Zhao³

2013

Front Biosci

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“…The IL-23/IL-17 axis, therefore, is one of the main cytokine axes driving the pathogenesis of cancers [7], [8]. The receptor for IL-23 is composed of interleukin-12 receptor β1 (IL-12Rβ1), a common subunit shared with IL-12R, and a unique IL-23 receptor (IL23R) [9].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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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.

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“…In searching the cause of obesity‐increased cancer incidence, epidemiological studies identified many cancer risk factors. They include increased blood levels of insulin, insulin‐like growth factor‐1 (IGF‐1), oestrogen, cytokines interleukin (IL)‐1, IL‐6, IL‐17, tumour necrosis factor (TNF)‐alpha, adipokine leptin and other inflammatory markers (18–22). Decreased blood levels of adiponectin in obesity have also been demonstrated to be a critical alteration which is linked to cancer.…”

Section: Alterations Of Cancer Risk Factors In Obesitymentioning

confidence: 99%

Multiple signal pathways in obesity-associated cancer

2011

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Obesity is increasing worldwide and reaches to a large proportion of the population in developed countries. Thus, obesity-associated cancer has become a major health problem. Multiple cancer risk factors in obesity have been identified including insulin/insulin-like growth factor axis, adipokines and cytokines; and multiple intracellular signal pathways have been studied. However, the role of each signal pathway in obesity-associated cancer is controversial. In this review, the recent studies on signal pathways in obesity-associated cancer are summarized and a unified explanation is provided. Multiple risk factors could initially activate phosphoinositide 3-kinase (PI3K/Akt), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) pathways. With increased severity of obesity, mammalian target of rapamycin (mTOR), which is down-stream of both PI3K/Akt and MAPK, is highly activated. Activated mTOR in turn inhibits the PI3K/Akt pathway and further activates the STAT3 pathway. This may explain the activation of the PI3K/Akt pathway at the early stage of obesity and its inhibition at the later stage. mTOR inhibition may be used for cancer therapy, but it may be necessary to be combined with the PI3K/Akt inhibitor as decreased mTOR activity will release its feedback inhibition on the PI3K/Akt pathway, which is under the influence of multiple cancer risk factors in obesity. Thus, dual inhibitors of PI3K and mTOR may provide a novel approach.

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The IL-23/IL-17 axis may be important in obesity-associated cancer by way of the activation of multiple signal pathways

Cited by 9 publications

References 9 publications

Obesity-associated endometrial and cervical cancers

Obesity-associated endometrial and cervical cancers

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

Multiple signal pathways in obesity-associated cancer

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