Meta-analysis of IL-6 promoter polymorphisms and cancer risk in ethnicity 

Meta-analysis of IL-6 promoter polymorphisms and cancer risk in ethnicity 

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IL-6 is critical for tumorigenesis. However, previous studies on the association of IL-6 promoter polymorphisms with predisposition to different cancer types are somewhat contradictory. Therefore, we performed this meta-analysis regarding the relationship between IL-6 promoter single nucleotide polymorphisms and cancer susceptibility and prognosis....

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... results showed that rs1800795 was significantly associated with increased cancer risk in allelic, dominant, recessive and additive models (OR = 1.05, 95% CI: 1.01, 1.09, P = 0.007, allelic models respectively) ( Table 1). Subgroup analysis indicated that rs1800795 was associated with a significantly higher risk of cancer in Asia (OR = 1.05, 95% CI: 1.01, 1.10, P = 0.003, allelic models respectively) ( Table 2) and Caucasian (OR= 1.04, 95% CI: 1.02, 1.06, P < 0.001, allelic models respectively) ( Table 2) in all four gene model. Meanwhile, rs1800795 was significantly associated with increased risk of cervical cancer (OR = 1.13, 95% CI: 1.05, 1.21, P = 0.004, allelic models respectively) (Table 3), colorectal cancer (OR = 1.10, 95% CI: 1.02, 1.19, P = 0.014, allelic models respectively) (Table 3), breast cancer (OR = 1.08, 95% CI: 1.01, 1.19, P = 0.013, allelic models respectively) (Table 3), prostate cancer (OR = 1.08, 95% CI: 1.03, 1.13, P= 0.005, allelic models respectively) (Table 3), lung cancer(OR = 1.08, 95% CI: 1.02, 1.15, P = 0.003, allelic models respectively) (Table 3), glioma (OR = 1.28, 95% CI: 1.13, 1.46, P < 0.001, allelic models respectively) (Table 3), non- hodgkin's lymphoma (OR = 1.25, 95% CI: 1.01, 1.51, P = 0.049, allelic models respectively) ( Table 3) and hodgkin's lymphoma (OR = 1.22, ...
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... results showed that rs1800795 was significantly associated with increased cancer risk in allelic, dominant, recessive and additive models (OR = 1.05, 95% CI: 1.01, 1.09, P = 0.007, allelic models respectively) ( Table 1). Subgroup analysis indicated that rs1800795 was associated with a significantly higher risk of cancer in Asia (OR = 1.05, 95% CI: 1.01, 1.10, P = 0.003, allelic models respectively) ( Table 2) and Caucasian (OR= 1.04, 95% CI: 1.02, 1.06, P < 0.001, allelic models respectively) ( Table 2) in all four gene model. Meanwhile, rs1800795 was significantly associated with increased risk of cervical cancer (OR = 1.13, 95% CI: 1.05, 1.21, P = 0.004, allelic models respectively) (Table 3), colorectal cancer (OR = 1.10, 95% CI: 1.02, 1.19, P = 0.014, allelic models respectively) (Table 3), breast cancer (OR = 1.08, 95% CI: 1.01, 1.19, P = 0.013, allelic models respectively) (Table 3), prostate cancer (OR = 1.08, 95% CI: 1.03, 1.13, P= 0.005, allelic models respectively) (Table 3), lung cancer(OR = 1.08, 95% CI: 1.02, 1.15, P = 0.003, allelic models respectively) (Table 3), glioma (OR = 1.28, 95% CI: 1.13, 1.46, P < 0.001, allelic models respectively) (Table 3), non- hodgkin's lymphoma (OR = 1.25, 95% CI: 1.01, 1.51, P = 0.049, allelic models respectively) ( Table 3) and hodgkin's lymphoma (OR = 1.22, ...
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... analysis indicated that rs1800796 was significantly associated with increased risk of lung cancer (OR = 1.23, 95% CI: 1.11, 1.36, P = 0.002, allelic models respectively) (Table 4), prostate cancer (OR = 1.13, 95% CI: 1.04, 1.23, P = 0.002, allelic models respectively) ( Table 4) and colorectal cancer (OR = 1.07, 95% CI: 1.04, 1.23, P < 0.001, allelic models respectively) (Table 4) but not gastric cancer (OR = 1.03, 95% CI: 0.82, 1.29, P = 0.786, allelic models respectively) ( Table 4) in all four gene model. Furthermore, rs1800796 was associated with a significantly risk of cancer in Asia (OR = 1.08, 95% CI: 1.03, 1.14, P < 0.001, allelic models respectively) ( Table 2) and Caucasian (OR = 1.05, 95% CI: 1.01, 1.10, P-0.003, allelic models respectively) ( Table 2) in all four gene model. ...
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... analysis indicated that rs1800796 was significantly associated with increased risk of lung cancer (OR = 1.23, 95% CI: 1.11, 1.36, P = 0.002, allelic models respectively) (Table 4), prostate cancer (OR = 1.13, 95% CI: 1.04, 1.23, P = 0.002, allelic models respectively) ( Table 4) and colorectal cancer (OR = 1.07, 95% CI: 1.04, 1.23, P < 0.001, allelic models respectively) (Table 4) but not gastric cancer (OR = 1.03, 95% CI: 0.82, 1.29, P = 0.786, allelic models respectively) ( Table 4) in all four gene model. Furthermore, rs1800796 was associated with a significantly risk of cancer in Asia (OR = 1.08, 95% CI: 1.03, 1.14, P < 0.001, allelic models respectively) ( Table 2) and Caucasian (OR = 1.05, 95% CI: 1.01, 1.10, P-0.003, allelic models respectively) ( Table 2) in all four gene model. ...
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... analysis indicated that rs1800797 has significant association in breast cancer (OR = 1.14, 95% CI: 1.06, 1.23, P = 0.002, allelic models respectively) ( Table 5), non-Hodgkin's lymphoma (OR = 1.09, 95% CI: 1.03, 1.05, P = 0.006, allelic models respectively) ( Table 5), B-NHL (OR= 1.10, 95% CI: 1.03, 1.18, P = 0.006, allelic models respectively) ( Table 5) and DLCBL (OR = 1.10, 95% CI: 1.01, 1.20, P = 0.006, allelic models respectively) ( Table 5) but not gastric cancer (OR = 1.04, 95% CI: 0.93, 1.15, P = 0.530, allelic models respectively) ( Table 5) in all four gene model. Besides, rs1800797 was associated with a significantly higher risk of cancer in Caucasian (OR= 1.04, 95% CI: 1.01, 1.08, P = 0.041, allelic models respectively) ( Table 2) but not in Asia (OR = 1.23, 95% CI: 0.79, 2.04, P = 0.326, allelic models respectively) ( Table 2) in all four gene model. ...
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... analysis indicated that rs1800797 has significant association in breast cancer (OR = 1.14, 95% CI: 1.06, 1.23, P = 0.002, allelic models respectively) ( Table 5), non-Hodgkin's lymphoma (OR = 1.09, 95% CI: 1.03, 1.05, P = 0.006, allelic models respectively) ( Table 5), B-NHL (OR= 1.10, 95% CI: 1.03, 1.18, P = 0.006, allelic models respectively) ( Table 5) and DLCBL (OR = 1.10, 95% CI: 1.01, 1.20, P = 0.006, allelic models respectively) ( Table 5) but not gastric cancer (OR = 1.04, 95% CI: 0.93, 1.15, P = 0.530, allelic models respectively) ( Table 5) in all four gene model. Besides, rs1800797 was associated with a significantly higher risk of cancer in Caucasian (OR= 1.04, 95% CI: 1.01, 1.08, P = 0.041, allelic models respectively) ( Table 2) but not in Asia (OR = 1.23, 95% CI: 0.79, 2.04, P = 0.326, allelic models respectively) ( Table 2) in all four gene model. ...

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... The study revealed a significant difference in IL-6 (rs1800795) genotypes and alleles between cases and controls. In addition, a meta-analysis study has confirmed that the IL-6 rs1800795 has a significant linkage with elevated lung cancer incidence (P = 0.003, for alleles) and in Caucasian and Asian populations (P < 0.001, P = 0.003, for alleles, respectively) (Peng et al., 2018). ...
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Lung cancer is a serious health and life issue, with the highest rates of incidence and mortality in the world. It is now clear that inflammation is a key factor involved in all aspects of carcinogenesis, notably lung cancer development. Genetic changes, including polymorphisms in inflammatory genes, are supposed to play a significant role in increasing lung cancer risk. In this study, we aim to investigate the association of IL-6 rs1800795 and IL-1β rs16944 polymorphisms with non-small cell lung cancer (NSCLC) development in the Egyptian population. The study design was composed of 100 NSCLC cases and 100 controls, which were genotyped using the ARMS-PCR technique, electrophoresed on a 2.5% agarose gel, and visualized using ethidium bromide under ultraviolet illumination. The IL-1β rs16944 genotypes were significantly different in NSCLC patients as compared to healthy controls (p = 0.032). Whereas the genotypes and alleles of the IL-6 rs1800795 were not significantly linked to NSCLC incidence (p = 0.726; p = 0.822, respectively). To our best knowledge, this study aimed to uncover the great impact of IL-1β rs16944 genotypes on NSCLC development in the Egyptian population; thus, it may be a gateway for earlier NSCLC prevention.
... In addition, the -174G>C polymorphism showed an important factor in reducing endotoxin-induced IL-6 release. They reported that the polymorphisms at position -597 and -174 were associated with IL-6 levels in endotoxin-stimulated cells and that polymorphism at position -572 did not affect IL-6 levels in leukocytes 25 In the study of Boeta-Lopez et al., as correlated with our study; in subjects with plasma IL-6 levels compared, they found a significantly higher level of IL-6 in patients with -597A allele than those with G allele 27 . In our study, a statistically significant difference was found control group and patient group for -597G>A polymorphism. ...
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Purpose: This study aims to appraise IL-6 gene expression in pleural fluid samples and establish a connection between expression levels and promoter polymorphisms for more accurate pleural effusion classification. Materials and Methods: A total of 38 adult patients (transudate (19) and exudate (19)) with pleural fluid and 33 healthy controls were included in the study. For the IL-6 gene expression study, RNA was isolated from transudate and exudate pleural fluids, and expression levels were compared between the two groups. Then, -174G>C (rs1800795), -572G>C (rs1800796) and, -597G>A (rs1800797) polymorphisms were analyzed using LightCycler® 480 II with real-time polymerase chain reaction from genomic DNA of controls and patients. Results: IL-6 levels were 7.13-fold more expressed in the exudate group than in the transudate group. No significant difference was found between the transudate-exudate groups in terms of polymorphisms. However, when we compared the transudate-exudate patient groups with the control groups, -174 G>C polymorphism and -597 G>A polymorphism were statistically significant. Conclusion: Pleural effusion treatment initiates with fluid characterization. In challenging cases, the current parameters are inadequate. Our findings indicate that IL-6 is a robust biomarker, independently distinguishing exudative and transudative states, surpassing traditional criteria. IL-6 shows promise for precise pleural effusion characterization, offering insights into pathophysiology and enabling targeted therapeutic interventions.
... In recent decades, in the process of exploring new methods for the diagnosis and treatment of B-NHL, particularly DLBCL, the number of studies on IL-6, IL-10, TNF-α and IFN-γ has gradually increased. IL-6 is a potent cytokine that promotes the growth and differentiation of B lymphocytes, and is an essential component of the lymphoma microenvironment; it also induces angiogenesis in tumors, disrupts adhesion between tumor cells, and strongly counteracts antitumor actions in the body, thereby promoting the growth and proliferation of tumor cells, while inhibiting apoptosis, initiating a vicious cycle (17,18). Although IL-10 is known to possess antitumor effects mediated by CD8 + T-cell responses, in the presence of CD19 + tumor cells, IL-10 can potentially serve as a growth factor for tumorigenic B lymphocytes, and promote the immune escape of tumor cells (19,20). ...
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The objective of the present study was to assess the levels of circulating cytokines in patients with diffuse large B-cell lymphoma (DLBCL), and to examine the associations between the cytokine levels, clinicopathological manifestations and patient prognosis. The study enrolled 49 patients with DLBCL, 11 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and 67 healthy controls from Zhejiang Provincial People's Hospital (Hangzhou, China) between January 2017 and January 2020. The serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were measured using flow cytometry. The IL-6, IL-10 and IFN-γ levels were significantly raised in patients with DLBCL compared with those in the healthy controls (P<0.05). The levels of IL-10 were significantly higher in patients with raised levels of circulating lactate dehydrogenase (P<0.05), while increases in both IL-6 and IL-10 were associated with raised C-reactive protein (CRP) levels, with IL-6 levels positively associated with those of serum CRP (P<0.01; r=0.66). Additionally, International Prognostic Index (IPI) risk stratification of patients with DLBCL was strongly associated with circulating IL-6 and IL-10 levels. Raised IL-6, IL-10 and TNF-α levels were linked with worse short-term treatment efficacies (P<0.05). Moreover, the accuracy of the model predicting short-term treatment response in patients with DLBCL, obtained using the support vector machine algorithm, was 81.63%. It was also found that raised serum IL-6 and IL-10 levels, together with reduced levels of IL-17, were associated with survival of <1 year in patients with DLBCL (P<0.05), although no significant link was found between cytokine levels and long-term overall survival. In conclusion, the serum levels of IL-6, IL-10, IL-17, TNF-α and IFN-γ can potentially serve as biological indicators of DLBCL tumor immune status, and combined application with the IPI score can be a robust prognostic indicator in patients with DLBCL.
... In a metaanalysis of IL-6 promoter genetic variants in cancer risk and prognosis, rs1800797 was found to have a significant association in BC (OR = 1.14). 10 Another study discovered that postmenopausal women with the rs1800797 AA genotype were prone to develop BC, even if they had not been exposed to hormones. In addition, the genotyping model revealed a remarkable correlation between IL-6 rs1800797 genotypes and ER (p < 0.05) and PR (p < 0.05) status in a single-locus analysis. ...
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Background and Aims Breast cancer is one of the deadliest diseases affecting women in Bangladesh, and its prevalence is increasing year by year. Although several IL‐6 single nucleotide polymorphisms have been implicated in BC susceptibility and prognosis in various studies, no research has been done to investigate the relationship between breast cancer and IL‐6 in Bangladeshi women. This investigation aimed to explore the linkage between the rs1800797 variant of IL‐6 and the susceptibility to breast carcinoma among women in Bangladesh. Methods The IL‐6 rs1800797 variant was genotyped in 218 subjects (110 cases and 108 controls) using the tetra‐primer ARMS‐PCR method. The statistical analysis was applied utilizing the SPSS software version 24.0. UALCAN database was used for IL‐6 mRNA analysis, and genotype‐based gene expression was retrieved from GTEx Portal. Results This study found a significant link between IL‐6 rs1800797 variants and increased chance of breast cancer across different genetic inheritance models, including additive model 1 (AG vs. GG: OR = 2.16, p = 0.035); dominant model (AG + AA vs. GG: OR = 2.26, p < 0.05); overdominant model (AG vs. GG + AA: OR = 2.08, p < 0.05); and allelic model (A vs. G: OR = 2.15, p < 0.05). However, an insignificant association of breast cancer was found in both additive model 2 (AA vs. GG: OR = 2.91, p > 0.05) and the recessive model (AA vs. GG + AG: OR = 2.52, p > 0.05). Under the analysis of the probability of false positive reports, no significant values were found in different models when the OR was 1.5, and the prior probability was 0.25. Conclusions A significant relationship was found between the IL‐6 rs1800797 genetic variant and the risk of breast cancer. However, the findings of the study should be further investigated with a larger sample size to validate the correlation.
... Our results were consistent with Kaanane et al. (2022), who discovered that the IL-6-174G > C (CC) genotype could boost lung cancer possibility in their Moroccan carriers. A meta-analysis study has confirmed that IL-6-174G > C is an independent risk factor for lung cancer prevalence in Caucasian (OR 1.04, p < 0.001) and Asian populations (OR 1.05, P = 0.003) (Peng et al. 2018). ...
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Lung cancer is a serious health and life issue, with the fastest-growing incidence and fatality rates worldwide. It is now clear that inflammation is a key factor involved in all aspects of carcinogenesis, notably lung cancer development. Genetic changes, including polymorphisms in inflammatory genes, are supposed to be a significant cause of increased lung cancer risk. The main idea of this research was to disclose the linkage between both IL-6 rs1800795 and IL-1β rs16944 variants and susceptibility to non-small-cell lung cancer (NSCLC) in Egyptians. This case–control design was composed of 127 cases and 138 controls, which were genotyped using the ARMS-PCR technique. To examine the NSCLC susceptibility under various genetic models, the odds ratio (OR) and 95% confidence intervals (CIs) were determined by logistic regression. Rs1800795 of the IL-6 gene was linked to higher odds of NSCLC under the allele model (adjusted, OR 2.28; 95% CI 1.2–4.33; p = 0.011). In the genetic models, IL-6 rs1800795 elevated the odds of NSCLC, while IL-1β rs16944 decreased the odds of NSCLC. Stratification analysis showed that IL-6 rs1800795 greatly increased the NSCLC risk in females and adenocarcinoma subtypes, whereas IL-1β rs16944 largely decreased the NSCLC risk for males, patients aged < 55, and nonsmokers. Regarding clinical data, the IL-6 variant was remarkably correlated with tumor size. This work primarily established that IL-6 and IL-1β variants have a great impact on NSCLC development in the Egyptian population; thus, it may be a supportive guide for earlier NSCLC prevention.
... IL-6 is the main risk factor involved in tumorigenesis. Nevertheless, earlier studies on the relationships of polymorphisms in IL-6 promoter through predisposition to various cancers are rather contrary (8). Indeed, the IL-6 gene is recognized as a pro-inflammatory cytokine and has a significant function in the pathogenesis of numerous cancer types (8). ...
... Nevertheless, earlier studies on the relationships of polymorphisms in IL-6 promoter through predisposition to various cancers are rather contrary (8). Indeed, the IL-6 gene is recognized as a pro-inflammatory cytokine and has a significant function in the pathogenesis of numerous cancer types (8). ...
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Background & Objective Interleukin-6 (IL-6) is involved in inflammation and has a significant role in chronic lymphocytic leukemia (CLL) progression. Accordingly, IL-6 level may increase in CLL-affected patients compared to healthy individuals. The -174G>C single nucleotide polymorphism (SNP) in IL-6 promoter region has been related to differences in IL-6 transcription. Therefore, we investigated the possible association of IL-6 polymorphism with CLL. Methods We examined the -174G>C SNP in IL-6 gene and studied its possible relationship with CLL in affected patients and in healthy controls using Amplification Refractory Mutation System- polymerase chain reaction genotyping method. IL-6 plasma level was measured in both studied groups. Results According to the results, IL-6 mean plasma concentration was increased significantly in the CLL patients compared to the controls. However, 174G>C genotype of the IL-6 gene was not associated with CLL. Furthermore, there were no significant differences in the distribution of allele and genotype frequencies between the CLL-affected patients and the controls (P>0.05). Conclusion Our study showed that -174G>C SNP in promotor of IL-6 gene could not be considered a risk factor for CLL. Larger prospective studies should be performed to confirm our results.
... Many studies have reported the association of various IL6 haplotypes, including variant alleles of rs1800797, rs1800796, and rs1800795, with diseases such as type 2 diabetes mellitus (Saxena et al., 2014), renal dysfunction (Ng et al., 2008), obesity (Boeta-Lopez et al., 2017), asthma (Lajunen et al., 2018), etc., all of which are COVID-19 comorbidities. Additionally, these promoter polymorphisms are associated with various cancer risks and prognoses, such as cervical cancer, colorectal cancer, breast cancer, prostate cancer, lung cancer, glioma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, Bcell lymphoma, and diffuse large B-cell lymphoma (Peng et al., 2018). ...
... For example, one meta-analysis did not find rs1800797 to be a risk factor for cancer (Qian et al., 2017). In contrast, another meta-analysis reported that rs1800797 is associated with a higher risk of cancer in Caucasians (Peng et al., 2018). Second, the association between SNP and a particular disease may depend on ethnicity. ...
... Second, the association between SNP and a particular disease may depend on ethnicity. For example, rs1800795 and rs1800796 are associated with an elevated risk of cancer in Caucasians and Asians, but rs1800797 increases the risk of cancer only in Caucasians (Peng et al., 2018). Third, different alleles at the same SNP locus can increase the risk of diseases. ...
Article
The severity of the coronavirus disease 2019 (COVID-19) is linked to pro-inflammatory cytokine levels. There are still many unanswered questions regarding COVID-19 pathogenesis and prognosis. Significantly increased levels of pro-inflammatory cytokines characterize severe COVID-19 compared to those with a mild-to-moderate form of the disease. In this study, we used in silico tools to explore the variant allele frequency distributions of three important pro-inflammatory cytokine genes: interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNFA), as well as their linkage disequilibrium (LD) patterns in worldwide populations. These cytokines were chosen for their pro-inflammatory properties, importance in determining COVID-19 outcomes, and potential as disease treatment targets. Twenty-two of the variants correlate with altered cytokine expression levels, which may also influence the expression of several other mediators of immune responses. These variants also appear to be associated with several COVID-19 comorbidities, such as diabetes, asthma, obesity, and heart conditions. At least one variant (rs1800795 in IL6) is likely associated with an altered response to TNFA inhibitors, which are considered COVID-19 treatment options. The European super-population has high variant allele frequencies (VAF ≥ 0.2) at thirteen of these variant loci. High genetic heterogeneity at these loci is present in the admixed American populations, whereas the East Asian populations appear genetically more homogeneous. Interethnic differences are more pronounced at the IL6 SNP loci, which may cause variances in the expression level of a long non-coding RNA gene, IL6-AS1. Stronger and more extensive LD (R2 ≥ 0.8) exists among the IL6 and IL8 variants in the European super-population and among the TNFA variants in the East and South Asian populations. In general, the European super-population has higher frequencies of haplotypes with multiple variant alleles. Such interethnic differences may shed more light on the disparities in COVID-19 severities and the responses to treatments across ethnic groups. J. Bangladesh Acad. Sci. 47(1); 69-90: June 2023
... IL-6 is a potent cytokine that accelerates the growth and differentiation of B lymphocytes, and it is an essential component of the lymphoma microenvironment. It also induces tumor blood vessel formation, destroys adhesion between tumor cells, and strongly prevents the anti-tumor effect of the body, thereby promoting growth, differentiation, and anti-apoptosis of tumor cells, which initiates a vicious cycle [11,12]. Although IL-10 is known to possess antitumor effects mediated by CD8 + T cell responses, in the presence of CD19 + tumor cells, elevated IL-10 levels can potentially serve as a growth factor for tumorigenic B lymphocytes, and facilitate tumor cells to escape the immune system in an autocrine form [13,14]. ...
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Objective To assess the contents of circulating cytokines in patients with diffuse large B-cell lymphoma (DLBCL), and to examine their relationship with clinicopathological manifestations and prognosis. Method We recruited 72 DLBCL patients, 11 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients, and 56 healthy controls from our hospital between the period of January 2017 and January 2020, and measured 7 serum cytokine contents using Beckman Navios flow cytometry. The cytokine level was compared between DLBCL patients and healthy controls using one way ANOVA. Two-sided Spearman test was employed for relationship evaluation between circulating cytokine levels and clinicopathological characteristics, IPI score, and short-term treatment response within DLBCL patients. The inter-group comparison of cytokine levels employed the Mann Whitney test. The support vector machine (SVM) was utilized for the cytokine evaluation-based prediction of DLBCL patient short-term treatment response. Lastly, survival curves were used to assess correlation between the aforementioned cytokines and overall survival. Result The IL-6, IL-10, and IFN-γcontents were markedly enhanced among DLBCL patients, as opposed to healthy controls (P < 0.05). Patients with enhanced circulating LDH expressed elevated IL-10 level (P < 0.05), and patients with augmented CRP expressed upregulated IL-6 and IL-10 levels, and the rise in IL-6 levels was positively associated with serum CRP (P = 0.00, r = 0.66). Additionally, the international prognostic index (IPI) risk stratification of DLBCL patients was strongly associated with the circulating IL-6 and IL-10 contents. Enhanced IL-6, IL-10, and TNF-α levels often produced worse short-term treatment efficacies (P < 0.05). Moreover, the accuracy of short-term treatment response prediction model of DLBCL patients, obtained using SVM, was 81.63%. Using long-term follow-up, we further revealed that the DLBCL patients who expired within one year exhibited enhanced circulating IL-6 and IL-10 levels, compared to patients who survived, however, the IL-17 level was drastically reduced (P < 0.05). Despite the aforementioned evidences, we observed no marked association between the specified cytokines and overall survival (OS). Conclusion The IL-6, IL-10, IL-17, TNF-α, and IFN-γ contents can potentially serve as biological indicators of DLBCL tumor immune status, and a combined application with the IPI score can be a robust indicator for DLBCL patient prognosis. Our findings provide novel ideas for the clinical treatment of DLBCL patients.
... 8 Elevated levels of IL-6 have been found in tumor tissues [9][10][11] and several singlenucleotide polymorphisms (SNPs) in the IL-6 gene have been implicated with increased risk of cervical cancer. 6,[12][13][14] Two promoter polymorphisms, rs1800795 (−174G/C) and rs1800797 (−597A/G), the IL-6 gene have been associated with a wide variety of malignancies, 15,16 including cervical cancer. 14,17,18 These two SNPs are located in the 5′ flanking region (7p15.3) of the IL-6 gene promoter. ...
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Background and Aims Cervical cancer is characterized by abnormal cell growth in the lining of cervix and it is the second major cause of cancer‐related deaths among females in Bangladesh. Interleukin‐6 (IL‐6) is a multifunctional cytokine that has been heavily linked with cervical cancer. Our aim was to investigate the association of two promoter single‐nucleotide polymorphisms (SNPs) of IL‐6 (rs1800795 and rs1800797) with the susceptibility of cervical cancer in Bangladeshi women. Methods DNA was extracted from venous blood samples from cervical cancer patients (n = 126) and healthy controls (n = 120). Polymerase chain reaction‐restriction fragment length polymorphism was used for genotyping of the selected SNPs. Logistic regression was performed to calculate the odds ratio (OR) with 95% confidence interval (CI) and p values. Results We found a significant association between rs1800795 and rs1800797 polymorphisms and cervical cancer. For, rs1800795 (G > C) the GC heterozygous genotype (OR = 2.80, 95% CI = 1.55–5.07, p = 0.0007) and CC mutant homozygous genotype (OR = 3.5, 95% CI = 1.29–9.51, p = 0.014) conferred an increased risk of cervical cancer. In case of rs1800797 (G > A) polymorphism, the AG heterozygous genotype (OR = 6.94, 95% CI = 3.76–12.81, p < 0.0001) and AA mutant homozygous genotype (OR = 3.88, 95% CI = 1.12–13.51, p = 0.0332) also exhibited an elevated risk of cervical cancer. Use of contraceptives was found as risk factor and patients who smoke were carriers of both the risk alleles and thus had an increased risk of cervical cancer. Conclusion Our findings suggest that polymorphism of rs1800795 and rs1800797 of the IL‐6 gene play a significant role in cervical cancer susceptibility in Bangladeshi women.
... However, data on the association of the -174G/C polymorphism of the IL6 gene with the risk of developing malignant neoplasms remain controversial [26], and interpopulation differences in allele frequencies may be one of the reasons for the existing contradictions [27]. It has been shown that for people of Tatar ethnicity of postmenopausal age, the homozygous -174G/-174G genotype serves as a marker of a reduced risk of developing ovarian cancer [28], while in Caucasians with non-alcoholic steatohepatitis and hepatocarcinoma, the frequency of IL6 -174G is significantly lower than in healthy people [5,29,30]. ...
Article
The study of immune response and inflammation gene polymorphisms in a genogeographic context is relevant in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants -174G/C (rs1800795) and -572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of the -174G and -572C alleles, which determine increased inflammatory response and are also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in the European and East-Asian groups. We hypothesize an adaptive role of these IL6 genetic variants in human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and the increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is likely increased.