Аналіз зв’язку однонуклеотидного поліморфізму rs4977574 гена довгої некодуючої РНК ANRIL із виникненням раку передміхурової залози

Abstract

The purpose of the study was to investigate the possible association between ANRIL gene rs4977574-polymorphism and prostate cancer occurrence among men of the Ukrainian population. Materials and methods. A total of 250 males were enrolled in the study. Of these, the experimental group included 184 prostate cancer patients, and the control group included 66 men without a history of malignant tumors. Genotyping of the ANRIL rs4977574 locus was performed by real-time polymerase chain reaction. The reaction was performed on a Quant Studio 5 DX Real-Time instrument (Applied Biosystems, USA) in the presence of TaqMan assays (TaqMan®SNP Assay C_31720978_30). The genotyping results were statistically processed using the SPSS software package (version 17.0). Values of p less than 0.05 were considered as statistically significant. Results and discussion. ANRIL (Antisense Non-coding RNA in the INK4 Locus), also known as CDKN2B-AS1, is a long non-coding RNA (3.8-kb) transcribed from the short arm of the human chromosome 9 (p21.3). ANRIL transcripts promote their main molecular effects through interaction with proteins of Polycomb repressive complex 1 and Polycomb repressive complex 2. Ultimately, this leads to epigenetic cis-inactivation of the tumor growth suppressor genes located in the Chr9p21 region: CDKN2A/p16INK4A, CDKN2A/p14ARF, CDKN2B/p15INK4B. Recent experimental studies have demonstrated the involvement of ANRIL in the development of malignant tumors of different localization. At the same time, there is almost no information about the role of the gene polymorphisms of this RNA in the occurrence of prostate cancer. The possible link between ANRIL gene polymorphism and prostate cancer risk in the Ukrainian population is not fully understood. It was found that the control men and prostate cancer patients did not differ significantly in the frequency of rs4977574-genotypes (p = 0.886). No significant difference was found during the corresponding comparison separately among persons with normal weight, overweight, without, and with the habit of smoking (p >0.05). Analysis of the association of different rs4977574 genotypes of the ANRIL gene with the risk of prostate cancer using logistic regression also did not show a reliable relationship under different models of inheritance, both before and after adjustment for age, body mass index and smoking (p >0.05). Conclusion. Thus, for the first time, we performed an analysis of the relation between ANRIL gene polymorphism and the development of malignant tumors of the genitourinary system in the Ukrainian population. The results showed that the polymorphic locus rs4977574 is not associated with the risk of prostate cancer