Joint Effects of Epstein-Barr Virus and Polymorphisms in Interleukin-10 and Interferon-γ on Breast Cancer Risk

He, Jianxing; Chen, Lijuan; Su, Yi; Cen, Yu-Ling; Tang, Lu-Ying; Yu, Dandan; Chen, Weiqing; Wang, Shenming; Song, Erwei; Ren, Ze-Fang

doi:10.1093/infdis/jir710

Cited by 23 publications

(17 citation statements)

References 45 publications

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“…In this study, we uncovered a new significance of the peripheral and tumoral global EBV load, which appeared to represent not only a harmless passenger, as suggested by others [12], but also a contributory function to the body’s immune reaction against the tumor. Interestingly, a recent report noted that the EBV may contribute to the risk of BC, and that this contribution may be modified by genetic variations in IFN-γ [42]. In our study, the most critical results were the frequency of interferon-γ producing PBMCs in non-relapsing patients with detectable EBV in blood and tumor tissue.…”

Section: Discussionmentioning

confidence: 59%

Epstein-Barr virus infection and clinical outcome in breast cancer patients correlate with immune cell TNF-α/IFN-γ response

Marrão

Habib

Paiva³

et al. 2014

BMC Cancer

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BackgroundFor nearly two decades now, various studies have reported detecting the Epstein-Barr virus (EBV) in breast cancer (BC) cases. Yet the results are unconvincing, and their interpretation has remained a matter of debate. We have now presented prospective data on the effect of EBV infection combined with survival in patients enrolled in a prospective study.MethodsWe assessed 85 BC patients over an 87-month follow-up period to determine whether EBV infection, evaluated by qPCR in both peripheral blood mononuclear cells (PBMCs) and tumor biopsies, interacted with host cell components that modulate the evolution parameters of BC. We also examined the EBV replicating form by the titration of serum anti-ZEBRA antibodies. Immunological studies were performed on a series of 35 patients randomly selected from the second half of the survey, involving IFN-γ and TNF-α intracellular immunostaining tests performed via flow cytometry analysis in peripheral NK and T cells, in parallel with EBV signature. The effect of the EBV load in the blood or tumor tissue on patient survival was analyzed using univariate and multivariate analyses, combined with an analysis of covariance.ResultsOur study represents the first ever report of the impact of EBV on the clinical outcome of BC patients, regardless of tumor histology or treatment regimen. No correlation was found between: (i) EBV detection in tumor or PBMCs and tumor characteristics; (ii) EBV and other prognostic factors. Notably, patients exhibiting anti-ZEBRA antibodies at high titers experienced poorer overall survival (p = 0.002). Those who recovered from their disease were found to have a measurable EBV DNA load, together with a high frequency of IFN-γ and TNF-α producing PBMCs (p = 0.04), which indicates the existence of a Th1-type polarized immune response in both the tumor and its surrounding tissue.ConclusionsThe replicative form of EBV, as investigated using anti-ZEBRA titers, correlated with poorer outcomes, whereas the latent form of the virus that was measured and quantified using the EBV tumor DNA conferred a survival advantage to BC patients, which could occur through the activation of non-specific anti-tumoral immune responses.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-665) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 59%

Epstein-Barr virus infection and clinical outcome in breast cancer patients correlate with immune cell TNF-α/IFN-γ response

Marrão

Habib

Paiva³

et al. 2014

BMC Cancer

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“…This result suggests that EBV may be a risk factor and its contribution is further modulated by genetic variations in the IFNG and IL10 genes. 16 Recent profiling of the IFNG genotypes showed correlation with imatinib therapy in chronic myeloid leukemia (CML) and predicts cytogenetic and molecular response to the disease. This suggests a probable contribution of the IFN-γ signaling pathway in the mechanism of action of imatinib in CML.…”

Section: Association With Human Diseasesmentioning

confidence: 99%

Cytokines of the Immune System

Dembić

2015

The Cytokines of the Immune System

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“…Aunque el rs2069705 en el gen IFNG se ha asociado previamente con las diferencias en el IFN-γ como reacción a una infección viral (52), no se halló evidencia de la asociación entre sus variantes y tales niveles, lo cual puede deberse a que la proteína NS1, como en el caso de otros flavivirus, puede haber inhibido la producción de IFN-γ, impidiendo una efectiva reacción antiviral (53).…”

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“…Las frecuencias del alelo -308 A y del haplotipo -238 TNFA/LTA fueron mayores en los casos de dengue hemorrágico (24) en población venezolana y tailandesa, respectivamente (18,20). Localizado en el cromosoma 12, el gen IFNG codifica la citocina IFN-γ, fundamental en la defensa contra el virus (25). La variante -1615 C/T en la región promotora, se asoció con niveles séricos altos de IFN-γ, y la variante T/T del polimorfismo llamado rs2430561 (reference sequence, rs), fue más frecuente en los casos de dengue hemorrágico (26).…”

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Variants in the TNFA, IL6 and IFNG genes are associated with the dengue severity in a sample from Colombian population

et al. 2017

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Introducción. La composición genética del huésped determina, entre otros aspectos, el perfil clínico del dengue, lo cual se debería al efecto de variantes en los genes que codifican citocinas proinflamatorias.Objetivo. Evaluar la asociación entre las variantes de tres polimorfismos en los genes candidatos TNFA, IL6 e IFNG con la gravedad del dengue en una población colombiana.Materiales y métodos. Se evaluaron los polimorfismos rs1800750, rs2069843 y rs2069705 de los genes TNFA, IL6 e IFNG, respectivamente, en 226 pacientes con dengue. Los genotipos se tipificaron usando la reacción en cadena de la polimerasa (PCR) y los polimorfismos de la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Para determinar el riesgo de diferentes fenotipos del dengue, se compararon las frecuencias alélicas con la prueba de ji al cuadrado, y los genotipos y los haplotipos, con regresión logística. Por último, los análisis se ajustaron utilizando datos de autoidentificación o del componente genético ancestral.Resultados. El alelo A del rs2069843, ajustado por autoidentificación, se asoció con casos de dengue hemorrágico en afrocolombianos. En la muestra completa, dicho polimorfismo, ajustado por componente genético ancestral, fue reproducible. Además, hubo asociaciones significativas entre las combinaciones alélicas GGT y GAC de los rs1800750, rs2069843 y rs2069705 en pacientes con dengue hemorrágico, con ajuste por componente genético ancestral y sin él. Además, la combinación alélica AGC produjo 58,03 pg/ml más de interleucina 6 que la GGC, independientemente de los componentes genéticos europeo, amerindio y africano.Conclusión. Las variantes de los polimorfismos GGT y GAC de los rs1800750, rs2069843 y rs2069705 en los genes TNFA, IL6 e IFNG, respectivamente, se correlacionaron con la gravedad del dengue en esta muestra de población colombiana.

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Joint Effects of Epstein-Barr Virus and Polymorphisms in Interleukin-10 and Interferon-γ on Breast Cancer Risk

Abstract: These results suggest that EBV may contribute to the risk of BC and that this contribution may be modified by genetic variations in IFN-γ.

Cited by 23 publications

References 45 publications

Epstein-Barr virus infection and clinical outcome in breast cancer patients correlate with immune cell TNF-α/IFN-γ response

Epstein-Barr virus infection and clinical outcome in breast cancer patients correlate with immune cell TNF-α/IFN-γ response

Cytokines of the Immune System

Variants in the TNFA, IL6 and IFNG genes are associated with the dengue severity in a sample from Colombian population

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