TNF GENE POLYMORPHISMS AFFECT THE PROGRESSION OF THE DISEASE IN BREAST CANCER PATIENTS

DOI: https://doi.org/None

E.V. Alferova (1,2), T.F. Malivanova (1), I.B. Kononenko (1), A.A. Vergun2, N.M. Kutuzova (2), L.V. Manzyuk (1), N.N. Mazurenko (1) 1 -N.N. Blokhin Russian Cancer Research Center, Kashirskoye Shosse, 24, Moscow, 115478, Russian Federation; 2 -Moscow State Pedagogical University, Malaya Pirogovskaya, 1, build. 1, Moscow, 119991, Russian Federation

Introduction. Tumor necrosis factor (TNF) plays a central role in the development of inflammatory and neoplastic processes. In the TNF gene promoter region there are -308(g/a) and -238(G/A) polymorphisms with different influence on the level of expression of TNF. The aim of the study was to investigate the effect of these polymorphisms on disease progression in patients with breast cancer (BC). Materials and methods. 82 breast cancer patients were included in the study. Allelic variants of -238(G/A) were determined by a RFLPPCR, the -308(G/A) polymorphism was analyzed by allele-specific PCR. Groups of carriers of combined genotypes -308/-238 TNF: ggGG, a*GG and ggAG were formed for comparison. Results. The distribution of genotypes -308/-238 TNF in BC patients with primary metastatic breast cancer (M1) significantly differed from cases without distant metastases (M0) (pχ2=0,03) due to the increase in the number of alternative genotypes (a*GG – from 26,4% in M1 to 60,0% in M0; ggAG – from 5,6% in M1 to 20,0% in M0). When analyzing the impact of TNF polymorphisms on recurrence-free survival of patients with early and locally advanced BC (M0), Luminal B subtype tumors carriers of both ggAG genotype (median 18.5 months), and agGG genotype (median 27 months) were found to have lower survival rates if compared with genotype ggGG (median 76 months) (pLogrank=0,02). Conclusion. Thus, the gene TNF polymorphisms -308(g/a) and -238(A/G) are associated with initially metastatic BC and reduced disease-free survival in patients with early and locally advanced disease, especially in cases with Luminal B subtype tumors.
Keywords: 
breast cancer (BC), tumor necrosis factor (TNF)
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