The correlation between TNF-α-308 gene polymorphism and susceptibility to cervical cancer

Li, Liping; Liu, Jie; Liu, Chunjing; Lu, Xianghui

doi:10.3892/ol.2018.8246

Cited by 12 publications

(11 citation statements)

References 23 publications

(21 reference statements)

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“…SNPs are the substitution of a single base pair for another and play a key role in the evaluation of disease susceptibility, drug efficacy, and adverse drug reactions 118 . Some investigators have analyzed the TNF‐α G>A rs1800629 SNP 119‐121 . According to Duarte et al, 119 the TNF‐α GA genotype showed a modest but statistically significant difference in genotype distribution (16.4% in controls vs 25.6% in patients with cervical cancer; n = 439; P = .012).…”

Section: Discussionmentioning

confidence: 99%

Blood‐based biomarkers of human papillomavirus–associated cancers: A systematic review and meta‐analysis

Balachandra¹,

Kusin²,

Lee

et al. 2020

Cancer

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Background Despite the significant societal burden of human papillomavirus (HPV)–associated cancers, clinical screening interventions for HPV‐associated noncervical cancers are not available. Blood‐based biomarkers may help close this gap in care. Methods Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full‐text review. Eligibility criteria included the assessment of a blood‐based biomarker within a cohort or case‐control study. Results One hundred thirty‐seven studies were included. Among all biomarkers assessed, HPV‐16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV‐associated cancers in comparison with cancer‐free controls. In most scenarios, HPV‐16 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40‐298.21; cOR for HPV‐unspecified OPC, 25.41; 95% CI, 8.71‐74.06; cOR for prediagnostic HPV‐unspecified OPC, 59.00; 95% CI, 15.39‐226.25; cOR for HPV‐unspecified cervical cancer, 12.05; 95% CI, 3.23‐44.97; cOR for HPV‐unspecified anal cancer, 73.60; 95% CI, 19.68‐275.33; cOR for HPV‐unspecified penile cancer, 16.25; 95% CI, 2.83‐93.48). Circulating HPV‐16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41‐72.57). In 3 cervical cancer case‐control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid. Conclusions HPV‐16 E6 antibodies and circulating HPV‐16 DNA are the most robustly analyzed and most promising blood‐based biomarkers for HPV‐associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type–specific, high‐risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high‐risk HPV types. Further investigation of blood‐based microRNA expression profiling appears indicated.

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Section: Discussionmentioning

confidence: 99%

Blood‐based biomarkers of human papillomavirus–associated cancers: A systematic review and meta‐analysis

Balachandra¹,

Kusin²,

Lee

et al. 2020

Cancer

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“…Al igual que nuestros resultados, no encontraron diferencias significativas en las frecuencias genotípicas y alélicas entre el grupo de pacientes con cáncer de cuello uterino y el grupo control; sin embargo, observaron que el genotipo A/A pudiera estar asociado con el incremento del riesgo de desarrollar cáncer de cuello uterino en 1,46 veces, con un intervalo de confianza del 95% de 0,32 a 6,67. Además, encontraron que pacientes con el alelo A tuvieron cáncer cervical de alto grado de malignidad (32).…”

Section: Discussionunclassified

“…Li y col. (32), también correlacionaron 5 polimorfismos en la región promotora del gen TNFα (rs361525, rs1800629, rs1800750, rs1799964, and rs673) con la susceptibilidad a desarrollar cáncer de cuello uterino, en 946 muestras de sangre periférica de mujeres de la etnia Han de la provincia de Shandong, de las cuales 452 fueron diagnosticadas con carcinoma cervical de células escamosas y 492 pacientes controles. Las muestras fueron analizadas empleando PCR SNP`s utilizando el método de la sonda TaqMan.…”

Section: Discussionunclassified

Polimorfismo -308 del gen TNFa y su expresión local en lesiones preinvasivas y cáncer de cuello uterino en el estado Zulia, Venezuela

Barrios¹,

Govea²,

Castillo³

et al. 2020

Invest Clin

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El Factor de Necrosis Tumoral Alfa (TNFα), es una citocina proinfla¬matoria; su expresión es regulada a nivel transcripcional y se han asociado algunos polimorfismos con la progresión de cáncer de cuello uterino (CCU). El objetivo de este estudio fue caracterizar el polimorfismo -308 del gen TNFa y su expresión local en lesiones preinvasivas y CCU. Se analizaron muestras de ADN de sangre periféri¬ca y biopsias de cuello uterino de 8 mujeres sanas y 33 con lesiones cervicales; el ADN se genotipificó mediante PCR-RFLP, empleando enzimas de restricción (NcoI) y, para su expresión en tejidos, se utilizó marcaje inmunohistoquímico. El polimor¬fismo -308 del gen TNFa se encontró en Equilibrio de Hardy-Weimberg tanto en casos como en controles. El genotipo más frecuente fue el A/A (60,6%), mientras el genotipo A/G representó el 39,4% del total de pacientes con lesión y no se detec¬tó genotipo G/G; así mismo, se encontró con mayor frecuencia el alelo A, 80,3%, mientras que el alelo G presentó una frecuencia del 19,7%. La expresión de TNFα por número de células positivas en tejidos fue heterogénea, observándose diferen¬cias estadísticamente significativas entre el grupo inflamatorio y NIC II (p<0,045). No existe asociación estadísticamente significativa entre el alelo A del polimorfismo -308 del gen TNFa (OR= 1,53; p = 0,585) con el CCU, así como entre el genotipo A/A y el CCU, pero para aclarar su papel en la carcinogénesis se necesitan realizar más estudios cuyo tamaño de la muestra sea mayor.

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“…TNF-α is a well-established driver of inflammation that may promote the growth and progression of cancer [27]. 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].…”

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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The correlation between TNF-α-308 gene polymorphism and susceptibility to cervical cancer

Cited by 12 publications

References 23 publications

Blood‐based biomarkers of human papillomavirus–associated cancers: A systematic review and meta‐analysis

Blood‐based biomarkers of human papillomavirus–associated cancers: A systematic review and meta‐analysis

Polimorfismo -308 del gen TNFa y su expresión local en lesiones preinvasivas y cáncer de cuello uterino en el estado Zulia, Venezuela

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

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