Genetic Variants of the IL2 Gene Related to Risk and Survival in Patients With Colorectal Cancer (original) (raw)

2019, Anticancer Research

Background: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). Materials and Methods: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. Results: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. Conclusion: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients. Colorectal cancer (CRC) is one of the most common types of malignancy worldwide (1). The pathogenesis of CRC is still not fully understood and the molecular mechanisms underlying tumor progression and metastasis are unclear. Cancer-related inflammation appears to be a hallmark of CRC and cytokines play a central role in the carcinogenic process since they are key regulators of immune responses (2, 3). Several interleukins (ILs) modulate intestinal tumor development, differentiation, and inflammatory and antiinflammatory responses. IL2 secreted by T-helper type 1 (Th1) cells is an important factor in activating T-cellmediated immune responses and stimulating the proliferation and differentiation of B-cells and natural killer cells. In addition, IL2 is involved in development of regulatory Tcells (Tregs) (4, 5). Genetic variation, such as single nucleotide polymorphisms (SNPs), of inflammatory genes is suggested to play a role in the risk of CRC and survival of patients (6, 7). Polymorphic variants within the IL2/IL21 region at 4q27 have been discovered to be related to multiple diseases. The SNP rs6822844 is positioned in the IL2/IL21 intergenic region and is associated with multiple autoimmune diseases (8, 9). SNP rs11938795 is located in the same IL2/IL21 block and is related to Crohn's disease (10). Another SNP of the IL2 gene, rs2069762, is located in the promoter region and is implicated in increased susceptibility to gastric (11), oral (12), nasopharyngeal (13) and breast cancer (14). A hot topic in CRC research is the search for clinically applicable biomarkers that can aid in diagnosis, prognostication and prediction of treatment response (15, 16). CRC staging is primarily based on the tumor-nodemetastasis (TNM) system of the American Joint Committee on Cancer (AJCC) classification system (17). Stage II CRC is generally considered as having a good prognosis, but a 4933 This article is freely accessible online.