*For correspondence: mustafayevn02@yahoo.co.uk
Nurmammad Mustafayev: https://orcid.org/0000-0002-8493-0429 Lala Akhundova: https://orcid.org/0000-0003-0553-3706 Shalala Majidova: https://orcid.org/0009-0009-2679-8333 Nigar Mammadli: https://orcid.org/0009-0007-5786-9654 Ahliman Amiraslanov: https://orcid.org/0009-0002-2504-9532 Irada Huseynova: https://orcid.org/0000-0003-3336-2203
One of the main tasks of modern medicine is to identify genetic predisposition to common diseases using molecular markers. This plays a crucial role in enabling early diagnosis and timely prevention. Currently, diseases that are either hereditary or non-hereditary, and which are caused by endogenous and exogenous factors, mutagenesis, and acute or chronic inflammatory processes, are the leading cause of both incidence and mortality. Of particular importance among these are various forms of cancer, which are associated not only with genetic factors but also with chronic inflammation. It is well established that proinflammatory cytokines, their biosynthesis and the proper functioning of signalling pathway components play a key role in the development and regulation of inflammatory processes, particularly chronic ones. In this context, along with agonists of interleukin-1 (IL-1), the interleukin-1 receptor antagonist (IL-1RA) and the gene encoding it (IL1RN) are critically involved in modulating IL-1 activity. The aim of the present study was to determine the association between the VNTR polymorphism (rs2234663) located in the second intron of the IL1RN gene and the risk of cancer presumably associated with chronic inflammation. The study material consisted of genomic DNA isolated from peripheral blood samples of cancer patients (experimental group, EG, n=80) and conditionally healthy individuals (control group, CG, n=84). Genotyping of the IL1RN VNTR polymorphism (rs2234663) was performed using the polymerase chain reaction (PCR) method with specific primers. Allele and genotype frequencies were calculated for both groups. Although all known alleles of the IL1RN gene were detected in the studied cohorts, several genotypes (*2*5, *2*6, *3*4, *3*5, *3*6, *4*5, *4*6, and *5*6) were not observed in either group. In the experimental group, the frequency of the normal allele *1 was approximately 1.4-fold lower, whereas the frequency of the mutant allele *2 was about 1.6-fold higher compared with the control group. Overall, the homozygous mutant genotype (*2*2) occurred approximately 2.1 times more frequently in cancer patients than in controls. To evaluate the strength of association between the IL1RN polymorphism and cancer susceptibility, odds ratios (OR), relative risks (RR), 95% confidence intervals (CI), Z-test statistics, and corresponding P values were calculated. The association between the risk allele *2 and cancer predisposition was statistically significant (OR≈2.2, RR≈1.53, P≈0.001). A pronounced association was also observed for the homozygous genotype *2*2 (OR≈2.84, RR≈2.18, P≈0.004). Notably, compared with heterozygous carriers (*1*2), individuals homozygous for the *2 allele (*2*2) exhibited approximately 2.4-fold higher odds (OR*2*2/OR*1*2) and about 2.0-fold higher relative risk (RR*2*2/RR*1*2) of developing cancer associated with chronic inflammation. Of the analysed genetic models, only the dominant model (*2*2 vs. *1*1 + *1*2) showed a statistically significant association with cancer risk (OR≈2.97, RR≈2.10, P=0.003).
We are thankful to all the patients and volunteers for providing blood samples. We are also grateful to the staff of the Oncology Clinic of Azerbaijan Medical University for their assistance in collecting samples and providing information about patients.
Nurmammad Mustafayev: scientific idea, conceptualization, study design, experimental procedures, discussion, and writing of the first draft. Lala Akhundova, Shalala Majidova, and Nigar Mammadli: sample collection, DNA isolation, genotyping, statistical analysis, and other experimental procedures. Ahliman Amiraslanov and Irada Huseynova: discussion, reviewing, and editing of the manuscript. Ahliman Amiraslanov: expert recom mendations and comments related to cancer disease.
The research followed the ethical principles of the Declaration of Helsinki. This study was approved by the ethics committees of the Institute of Molecular Biology and Biotecnologies, and the Oncology Clinic of the Azerbaijan Medical University, Ministry of Health of the Republic of Azerbaijan. Informed written consent was obtained from all the participants (patients and volunteers) included in the study. Besides, ethical issues including plagiarism, data fabrication and double publication were completely avoided by the authors.
This study did not receive any specific grant from the state, commercial or non-commercial organizations.
The authors declare that they have no conflicts of interest related to the publication of this manuscript.
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Received: November 05, 2025; Reviewed: December 15, 2025; Accepted: December 24, 2025
DOI:
https://doi.org/10.62088/timbb/9.2.3Keywords:
Inflammation, cytokine, interleukin-1, agonist, antagonist, risk allele, cancer, association
Mustafayev, N., Akhundova, L., Majidova, S., Mammadli, N., Amiraslanov, A., Huseynova, I.. (2025). ASSOCIATION OF THE IL1RN GENE VNTR POLYMORPHISM (RS2234663) WITH CHRONIC INFLAMMATION-ASSOCIATED CANCER. TIMBB, 9 (2), 21-31.