Medical Radiology and Radiation Safety. 2025. Vol. 70. № 5

DOI:10.33266/1024-6177-2025-70-5-98-103

T.F. Malivanova, T.A. Astrelina, I.V. Kobzeva, Y.B. Suchkova, D.Y. Usupzhanova,
V.A. Brunchukov, V.A. Nikitina, A.I. Golovkova, A.S. Ostashkin, E.S. Lubaeva,
M.Yu. Sukhova, Yu.D. Udalov

Heterogeneity of the Early Radiation-Induced Skin Damage to Adjuvant Radiation Therapy of Breast Cancer Patients Allele TNF-308A Carriers

A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia

Contact person: Tatyana Feodorovna Malivanova, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

ABSTRACT

Purpose: The use of ionizing radiation is a fundamental approach in the complex treatment of oncological diseases, including breast cancer (BC), the most common localization of malignancies in women. The degree of early radiation-induced skin damage (ERSD), a common complication of adjuvant radiation therapy (ART), can be considered as a criterion of individual radio sensitivity. An important link in the immune response to the damaging effects of ionizing radiation is the pro-inflammatory cytokine tumor necrosis factor (TNF). The TNF gene occupies a central position in the HLA gene complex and has a number of single-nucleotide polymorphisms. Approximately half of the carriers of the minor allele of TNF-308A/G polymorphism may be included in the ancestral haplotype AH8.1. The aim of the study was to assess the effect of polymorphisms of the TNF gene and genes of the HLA complex on the degree of ERSD in patients with breast cancer during the course of ART.

Material and methods: The study included 145 BC patients who underwent a course of ART (2 Gy in 25 fractions). The degree of ERSD was determined by a radiologist. Polymorphisms of genes TNF (–863C/A, –308G/A, –238G/A), HSPA1B+1267A/G and IKBL-62T/A and marker alleles of haplotype AH8.1 (HLA-A*01, HLA-B*08, HLA-DRB1*03) were determined by the PCR-SSP and PCR-RFLP.

Results: ERSD was detected in all BC patients during the course of ART: grade I – 57.9 %, grade II – 35.9 %, grade III – 6.2 %. Three genetic comparison groups were identified: carriers of the allele TNF-308A and simultaneously three marker alleles of haplotype AH8.1 (11.7 %); carriers of the allele TNF-308A without the AH8.1 haplotype (11.0 %); carriers of the wild allele homozygote TNF-308GG (77.3 %). The percentages of BC patients with grade II-III ERSD were significantly higher in carriers of the TNF-308A allele without the AH8.1 haplotype than in other BC patients (75.0 % and 38.0 %, respectively, p=0.0065; RR=1.97, 95 % CI [1.38, 2.83]). An increase in the proportion of BC patients with grade II-III ERSD with additional TNF-863CC homozygote to 85.7 %, compared with 37.4% for other breast cancer patients (p=0.0009), further increases the relative risk to RR=2.92, 95 % CI [1.68, 3.12]. The inclusion of other studied polymorphisms in the analysis did not have an additional effect.

Conclusion: For the first time, the heterogeneity of the reaction of allele TNF-308A carriers to radiation therapy has been revealed, which manifests itself depending on the inclusion or non-inclusion of this allele in the ancestral haplotype AH8.1 of the HLA complex. A genetic group with increased individual radio sensitivity has been identified as TNF-308A carriers without the haplotype AH8.1.

Keywords: adjuvant radiation therapy, early radiation-induced skin damage, breast cancer, tumor necrosis factor

For citation: Malivanova TF, Astrelina TA, Kobzeva IV, Suchkova YB, Usupzhanova DY, BrunchukovVA, Nikitina VA, Golovkova AI, Ostashkin AS, Lubaeva ES, Sukhova MYu, Udalov YuD. Heterogeneity of the Early Radiation-Induced Skin Damage to Adjuvant Radiation Therapy of Breast Cancer Patients Allele TNF-308A Carriers. Medical Radiology and Radiation Safety. 2025;70(5):98–103. (In Russian). DOI:10.33266/1024-6177-2025-70-5-98-103

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Conflict of interest. The authors declare no conflict of interest.

Financing. The study had no sponsorship.

Contribution. Article was prepared with equal participation of the authors.

Article received: 20.05.2025. Accepted for publication: 25.06.2025.