Genetically Predicted Circulating Levels of Cytokines and the Risk of Cancer

Song, Jié; Li, Aole; Yu, Qian; Liu, Bin; Lv, Linshuoshuo; Ye, Ding; Sun, Xiaohui; Mao, Yingying

doi:10.3389/fimmu.2022.886144

Cited by 18 publications

(11 citation statements)

References 43 publications

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“…Inverse variance weighted (IVW) analysis was used as the main MR analysis. The Cocrane’s Q test was used to determine whether SNPs were heterogeneous ( Song et al, 2022 ). In complementary analyses, weighted median and MR-Egger regression methods were used ( Larsson et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study

Wang

Zhu²,

Lin³

et al. 2023

Front. Cell Dev. Biol.

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Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is a causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate the causal relationship between systemic inflammatory regulators and ACLF. The study analyzed 41 cytokines and growth factors from 8,293 individuals extracted from a genome-wide association study (GWAS) meta-analysis database involving 253 ACLF cases and 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, lower basic fibroblast growth factor (bFGF) levels and higher Interleukin-13 (IL-13) levels were associated with an increased risk of ACLF (OR = 0.486, 95% CI = 0.264–0.892, p = 0.020; OR = 0.323, 95% CI = 0.107–0.972, p = 0.044; OR = 1.492, 95% CI = 1.111–2.004, p = 0.008, respectively). In addition, genetically predicted ACLF did not affect the expression of systemic inflammatory regulators. Our results indicate that cytokines play a crucial role in the pathogenesis of ACLF. Further studies are needed to determine whether these biomarkers can be used to prevent and treat ACLF.

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Section: Methodsmentioning

confidence: 99%

Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study

Wang

Zhu²,

Lin³

et al. 2023

Front. Cell Dev. Biol.

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“…Over-expression of IL-18 in serum has been reported to serve as a good marker for solid cancers, such as lung cancer (27); however, whether the serum level of IL-18 is a good marker for ALL is still unknow. There is evidence that high circulating levels of IL-18 associate with a decreased risk of AML (36). Dynamic alterations of IL-18 protein make it difficult to conclude whether IL-18 protein can serve as a good marker for ALL.…”

Section: Discussionmentioning

confidence: 99%

“…In 2022, high circulating levels of IL-18 were suggested as a potential predictor for decreased risk of acute myeloid leukemia (AML) (36). In 2017, IL-18 rs1946518 genotypes were reported to associate with prognosis and survival of AML (37), but to the best of our knowledge, there has been no study on IL-18 genotypes in association with ALL.…”

mentioning

confidence: 99%

Significant Contribution of Interleukin-18 Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwanese

Chen¹,

Tzeng²,

Kuo³

et al. 2022

Anticancer Res

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Background/Aim: Evidence has shown that has both antitumor and pro-tumor effects in various types of leukemia. The current study aimed at investigating the contribution of IL-18 polymorphisms to the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan. Materials and Methods: IL-18 promoter -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 266 childhood ALL cases and 266 controls were determined by polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The distributions of genotypic and allelic frequencies of IL-18 rs1946519, rs1946518 or rs187238, were not significantly different between childhood ALL cases and controls (all p>0.05). However, in the stratification analysis among the cases, IL-18 rs187238 GC and CC genotypes were associated with increased childhood ALL risk and shorter survival (OR=4. 19 and 2.93, p=0.0001 and 0.0250, respectively). No association was found with rs1946519 and rs1946518 (all p>0.05). Conclusion: IL-18 rs187238 GC and CC genotypes can serve as predictors for childhood ALL prognosis among Taiwanese. Validation in larger and various populations can greatly extend the feasibility of this novel predictor.Acute lymphoblastic leukemia (ALL) is a disease that arises from the uncontrolled proliferation of lymphoid progenitors (1, 2). Typically, ALL is the most prevailing pediatric hematologic malignancy and mainly attacks children aged 2-5 years old (3-5). Although the pathogenesis and etiology of childhood ALL remain largely unknown, it is widely believed that childhood ALL is caused by genetic variations and environmental factors (6, 7). Recently, lots of studies reported that subtle alterations in the inherited genome, single nucleotide polymorphisms (SNPs), may play a critical role in determining the personal susceptibility to childhood ALL (8-13). The genetic factors associated with childhood ALL are largely undefined, and further explorations of the roles of these factors in relation to childhood ALL are beneficial for early detection and prediction of the disease. Interleukin-18 (IL-18) was originally found in 1999 as a member of IL-1 cytokine family (14). It is secreted by various cells including T and B lymphocytes, monocytes, 5283

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“…To evaluate heterogeneity, we employed Cochran’s Q statistic, where a significant result is indicated by a p -value less than 0.05. This statistical test allows us to determine if there is substantial heterogeneity among the studies included in our analysis [ 27 ]. Additionally, we employed the MR-Egger regression to appraise horizontal pleiotropy, and considered a P value less than 0.05 to be significant [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Causal relationship of interleukin-6 and its receptor on sarcopenia traits using mendelian randomization

Chen,

Li,

Lin

et al. 2024

Nutr J

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Background Previous research has extensively examined the role of interleukin 6 (IL-6) in sarcopenia. However, the presence of a causal relationship between IL-6, its receptor (IL-6R), and sarcopenia remains unclear. Method In this study, we utilized summary-level data from genome-wide association studies (GWAS) focused on appendicular lean mass (ALM), hand grip strength, and walking pace. Single nucleotide polymorphisms (SNPs) were employed as genetic instruments for IL-6 and IL-6R to estimate the causal effect of sarcopenia traits. We adopted the Mendelian randomization (MR) approach to investigate these associations using the inverse variance weighted (IVW) method as the primary analytical approach. Additionally, we performed sensitivity analyses to validate the reliability of the MR results. Result This study revealed a significant negative association between main IL-6R and eQTL IL-6R on the left grip strength were − 0.013 (SE = 0.004, p < 0.001) and -0.029 (SE = 0.007, p < 0.001), respectively. While for the right grip strength, the estimates were − 0.011 (SE = 0.001, p < 0.001) and − 0.021 (SE = 0.008, p = 0.005). However, no evidence of an association for IL-6R with ALM and walking pace. In addition, IL-6 did not affect sarcopenia traits. Conclusion Our study findings suggest a negative association between IL-6R and hand grip strength. Additionally, targeting IL-6R may hold potential value as a therapeutic approach for the treatment of hand grip-related issues.

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Genetically Predicted Circulating Levels of Cytokines and the Risk of Cancer

Cited by 18 publications

References 43 publications

Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study

Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study

Significant Contribution of Interleukin-18 Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwanese

Causal relationship of interleukin-6 and its receptor on sarcopenia traits using mendelian randomization

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