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Autoimmune Haplotype AH8.1 Normalizes the Level of Tumor Necrosis Factor in the Blood Sera of Breast-Cancer Patients

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Abstract

Tumor necrosis factor (TNF) plays an important role in the pathogenesis of breast cancer (BC). The -308(G/A)TNF polymorphism allele -308A is part of the autoimmune ancestral haplotype AH8.1 associated with elevated serum sTNF levels. Previously, we showed a decrease in overall survival for carriers -308A/AH8.1-. The aim of the study was to assess the effect of haplotypes AH8.1 on the level of sTNF and clinical and morphological characteristics of BC patients. The study included 100 people with adjuvant radiotherapy treatment. The concentration of sTNF was determined by the ELISA. Additionally, 30 archival DNA samples of primary BC patients carrying the allele -308A with a known sTNF level were genotyped. Alleles -308(G/A)TNF and marker alleles of haplotype AH8.1 (HLA-A*01, HLA-B*08 and HLA-DRB1*03) were determined by allele-specific PCR. Based on the polymorphism of -308(G/A)TNF and marker alleles of haplotype AH8.1, three comparison groups were identified: -308GG carriers of the TNF gene independently of haplotype AH8.1 (76%), which were used as a control; -308A/AH8.1- carriers (9%); and -308A/M(AH8.1)+ carriers of at least one haplotype AH8.1 allele (15%). The comparison groups had no statistically significant differences regarding the stage of the disease, the degree of malignancy, the histological type, and the receptor status of the tumor. The level of sTNF was significantly higher in the genetic group -308A/AH8.1– both before surgery and before and after adjuvant radiotherapy. In BC patient carriers of the TNF gene allele -308A, the autoimmune haplotype AH8.1 has a normalizing effect on the production of sTNF to a level comparable to the level of cytokine in the group of carriers of the common -308GG genotype. The genetic group -308A/AH8.1– with an increased level of sTNF has been identified, for which, bearing in mind its prognostic unfavorability, anti-TNF therapy can presumably be offered. The results obtained can be used in the framework of personalized medicine.

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Authors and Affiliations

  1. State Research Center—Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, 123098, Moscow, Russia

    T. F. Malivanova, T. A. Astrelina, I. V. Kobzeva, V. A. Nikitina, Yu. B. Suchkova, A. S. Ostashkin, D. Yu. Usupzhanova, E. I. Dobrovolskaya, V. A. Brunchukov, A. A. Rastorgueva, E. E. Lomonosova, E. S. Lubaeva, E. Yu. Kretova, N. G. Stepanyants, M. Yu. Sukhova & A. S. Samoilov

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  1. T. F. Malivanova
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  2. T. A. Astrelina
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  3. I. V. Kobzeva
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  4. V. A. Nikitina
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  5. Yu. B. Suchkova
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  11. E. E. Lomonosova
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Correspondence to T. F. Malivanova.

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Statement of Compliance with Standards of Research involving Humans as Subjects

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Translated by A. Kazantseva

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Malivanova, T.F., Astrelina, T.A., Kobzeva, I.V. et al. Autoimmune Haplotype AH8.1 Normalizes the Level of Tumor Necrosis Factor in the Blood Sera of Breast-Cancer Patients. Mol. Genet. Microbiol. Virol. 38, 34–40 (2023). https://doi.org/10.3103/S089141682301007X

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