Tumor Necrosis Factor Alpha rs1800629 Polymorphism and Risk of Cervical Lesions: A Meta-Analysis

Li, Min; Han, Ying; Wang, Tingting; Feng, Yichen; Wang, Hongbo

doi:10.1371/journal.pone.0069201

Cited by 14 publications

(9 citation statements)

References 37 publications

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“…TNF-α is a highly pleiotropic cytokine with an important role in immune homeostasis, inflammation, and host defense (19). It is also involved in the defense against HPV infection by modifying viral replication (8), but unfortunately tumors can become TNF-α resistant. In fact, some malignant tumors are able to escape from TNF-α-induced cell death, suggesting that HPV-mediated TNF resistance is a key event in the multistep process leading to cervical cancer (19-20-21).…”

Section: Discussionmentioning

confidence: 99%

“…Tumor necrosis factors alpha (TNF-α) and beta (TNF-β) play a central role in the adaptive immune response. They are mainly secreted by activated macrophages and are able to promote the host's defense mechanism by activating inflammatory processes (8). Although a moderate TNF level is necessary to maintain cell protected and prevent certain diseases through regulation of the immune response, excessive TNF secretion due to pathological conditions is associated with autoimmune diseases, infectious diseases and malignant tumors (9).…”

Section: Introductionmentioning

confidence: 99%

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Association between Toll-like Receptor and Tumor Necrosis Factor Immunological Pathways in Uterine Cervical Neoplasms

Matos

Cândido

Vidigal

et al. 2016

Tumori

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Introduction The immune system plays a critical role in the defense against human papillomavirus (HPV) infection and its persistence. Toll-like receptors (TLRs) are membrane receptors responsible for activation of the innate immune response, and an association between TLR expression and uterine cervical cancer has been shown. Tumor necrosis factors (TNFs) are among the main mediators of skin and mucosa inﬂammation. The aim of this study was to demonstrate the association between TLR and TNF immune expression and cervical cancer and premalignant cervical lesions. Methods A total of 64 embedded tissues were obtained from gynecological procedures, including 35 specimens with cervical intraepithelial neoplasia (CIN) and 10 specimens with cervical squamous cell carcinoma (CSCC) as well as 19 normal cervical samples. The expression of TLR2, TLR3, TLR4, TNF-α and TNF-β was measured by immunohistochemistry and graded into low and high levels of expression. Results There was an association between the expression levels of TLR2 and those of TNF-α and TNF-β (p = 0.01 and p = 0.021, respectively) in the cervical cancer and CIN groups. TLR4 expression was associated with TNF-α and TNF-β expression (p = 0.016 and p = 0.025, respectively) in these 2 groups. By contrast, TLR3 was not statistically associated with TNF-α or TNF-β in any of the groups. Conclusions There might be an association of the TLR2 and TLR4 pathways with the immunological response of TNF-α and TNF-β in cervical cancer. These markers are also expressed at higher levels in cervical cancer and premalignant lesions compared to normal controls.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association between Toll-like Receptor and Tumor Necrosis Factor Immunological Pathways in Uterine Cervical Neoplasms

Matos

Cândido

Vidigal

et al. 2016

Tumori

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“…The two most commonly studied SNPs are in the promoter region of TNF , two G versus A transitions at positions −238 and −308; these have been shown to influence the expression of TNF-α [28,29]. A large number of studies have investigated the associations of TNF -238 G/A and/or −308G/A variants with cervical cancer risk, but results are contradictory [30,31]. Our data showed that −238 GG/GA and −308 AA genotypes in TNF were associated with increased cervical cancer risk.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms in tumor necrosis factor alpha and interleukin-10 are associated with an increased risk of cervical cancer

Wang

Richards

et al. 2019

International Immunopharmacology

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Most cases of cervical cancer are the result of infection with specific high-risk types of human papillomavirus (HPV). Investigating the genetic basis of the host immune response, particularly cytokine function, could help further characterize the progression of cervical HPV infection into neoplasia. Prior studies have demonstrated a correlation between genetic variants of tumor necrosis factor alpha (TNF-α, TNF gene) and/or interleukin-10 (IL-10, IL10 gene) and cervical cancer susceptibility. However, some of the results have been contradictory. We sought to resolve these discrepancies by carrying out our study in a large cohort of Chinese women. In order to assess the association of TNF and IL10 genotypes with cervical cancer susceptibility, the polymorphisms in TNF (−238 G/A, −308 G/A) and IL10 (−592 C/A, −819 C/T, −1082 A/G) were genotyped and odds ratios for the genotype and allele frequencies between cervical cancer patients and healthy controls were calculated. Also, the functional relevance of these polymorphisms was evaluated using enzyme-linked immunosorbent assays (ELISAs) and in vitro lymphocyte proliferation assays. The TNF-238 AA genotype frequency was lower in patients than in controls (p < 0.05). TNF-308 AA, IL10-592 CA/AA, and IL10-819 CC/CT genotype frequencies were higher in cervical cancer patients than in controls (p < 0.05). The frequency of the TNF-238 A allele was significantly lower in patients, while the frequency of the −308 A allele was significantly higher (p < 0.05). No significant differences between patients and controls were found in the genotype or allele frequencies of IL10-1082 A/G (p > 0.05). Furthermore, the combinations of TNF-238 GA or GG and IL10-592 CC; TNF-238 GA or GG and IL10-592 CA or AA; TNF-308 AA and IL10-592 CC; and TNF-308 AA and IL10-592 CA or AA in cervical cancer patients were statistically significant (p < 0.0167). Upon stimulation with PHA, peripheral blood mononuclear cells (PBMCs) with the TNF-308AA genotype exhibited significantly higher proliferation rates, elevated IL-4, TGF-β levels, and lower IL-2 levels (p < 0.05). For IL10-592C/A, the AA and CA genotypes were significantly associated with higher proliferation rates, elevated IL-4 and IL-10 levels (p < 0.05). We also found that for TNF-308 G/A or IL10-592 C/A variants, the combination of TNF-308 GG or GA with IL10 CA or AA had an association with the severity of cervical cancer. Taken together, these results suggest that TNF-308 AA and IL10-592 CA/AA genotypes may increase susceptibility to cervical cancer by altering the immune response of an individual.

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“…Common SNPs in the TNF-a promoter region have the ability to regulate the transcriptional activity. Such functional polymorphisms include TNF-a 308 and TNF-a -238G/A, and these have been associated with cervical cancer (Duarte et al, 2005;Li et al, 2013Li et al, , 2016Liu et al, 2012;Rotar et al, 2014).…”

Section: Tumor Necrosis Factor Alphamentioning

confidence: 99%

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

Kuguyo

Tsikai

Thomford

et al. 2018

OMICS: A Journal of Integrative Biology

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Human papillomavirus (HPV) is an essential but not a sufficient cervical cancer etiological factor. Cancer promoters, such as host genetic mutations, significantly modulate therapeutic responses and susceptibility. In cervical cancer, of interest have been viral clearing genes and HPV oncoprotein targets, for which conflicting data have been reported among different populations. This expert analysis evaluates cervical cancer genetic susceptibility biomarkers studied in African populations. Notably, the past decade has seen Africa as a hotbed of biomarker and precision medicine innovations, thus potentially informing worldwide biomarker development strategies. We conducted a critical literature search in PubMed/MEDLINE, Google Scholar, and Scopus databases for case-control studies reporting on cervical cancer genetic polymorphisms among Africans. We found that seven African countries conducted cervical cancer molecular epidemiology studies in one of Casp8, p53, CCR2, FASL, HLA, IL10, TGF-beta, and TNF-alpha genes. This analysis reveals a remarkable gap in cervical cancer molecular epidemiology among Africans, whereas cervical cancer continues to disproportionately have an impact on African populations. Genome-wide association, whole exome-and whole-genome sequencing studies confirmed the contribution of candidate genes in cervical cancer. With such advances and omics technologies, the role of genetic susceptibility biomarkers can be exploited to develop novel interventions to improve current screening, diagnostic and prognostic methods worldwide. Exploring these genetic variations is crucial because African populations are genetically diverse and some variants or their combined effects are yet to be discovered and translated into tangible clinical applications. Thus, translational medicine and flourishing system sciences in Africa warrant further emphasis in the coming decade.

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Tumor Necrosis Factor Alpha rs1800629 Polymorphism and Risk of Cervical Lesions: A Meta-Analysis

Cited by 14 publications

References 37 publications

Association between Toll-like Receptor and Tumor Necrosis Factor Immunological Pathways in Uterine Cervical Neoplasms

Association between Toll-like Receptor and Tumor Necrosis Factor Immunological Pathways in Uterine Cervical Neoplasms

Genetic polymorphisms in tumor necrosis factor alpha and interleukin-10 are associated with an increased risk of cervical cancer

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

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