Significance of −1082A/G polymorphism of IL10 gene for progression of colorectal cancer and IL-10 expression

Abstract

The role of functional polymorphism within IL10 (rs1800896) in colorectal cancer (CRC) still remains elusive. The aim of present study was to investigate the significance of -1082A/G polymorphism in IL10 on CRC risk, progression, and overall survival in a cohort of Bulgarian patients. Also, a functional role of this polymorphism on systemic and local level of IL10 mRNA quantity and serum IL-10 level was explored. A group of 119 patients with sporadic CRC and 154 age-sex-matched controls were genotyped by allele-specific PCR. The quantification of mRNA and serum IL-10 levels was performed by real-time PCR and ELISA assays, respectively. The genotype and allelic frequency among cases and controls was similar. However, we observed significant elevation of G-allele and GG-genotype frequencies among advanced CRC. G-allele was overrepresented in advanced CRC patients (49 %) compared to early CRC (35 %) with OR = 1.77; 95%CI 1.018 ÷ 3.083; P = 0.031. A significant upregulated expression of IL10 mRNA was observed among AG/GG-genotypes in tumor tissue compared to homozygous AA-genotype (RQ value 68.3 vs. 6.68; P = 0.0062). Also, GG-genotype of -1082A/G polymorphism in IL10 was positively associated with higher serum IL-10 among early CRC patients and controls, in contrast to advanced cases. Although, investigated polymorphism in IL10 has no significant impact of overall survival among Bulgarian CRC patients, we found a significant relationship of high pre-operative serum level of IL-10 with poor survival of CRC (P = 0.023). Our findings indicate a significant impact of -1082A/G polymorphism of IL10 on CRC progression, rather than genetic predisposition and prognosis of CRC.

Promoter polymorphisms in TGFB1 and IL10 genes influence tumor dendritic cells infiltration, development and prognosis of colorectal cancer

“…The most extensively studied IL10 ‐1080 A/G SNP in the promoter region has been associated with IL‐10 production. Several studies have reported consistently that the ‐1080G allele is correlated with increased IL‐10 serum levels as a result of a higher affinity for Sp1 transcription factor than the ‐1080A allele …”

“…It was suggested that the carriers of the G allele had a higher production of IL‐10 and, consequently, a lower risk for CRC . In addition, the same polymorphism was investigated as a factor influencing the CRC progression, tumor differentiation degree and CRC survival, although the results obtained were conflicting and insufficient …”

“…18,19 In addition, the same polymorphism was investigated as a factor influencing the CRC progression, tumor differentiation degree and CRC survival, although the results obtained were conflicting and insufficient. 20 An effective immune response against tumors requires the activation and consequent maturation of antigen-presenting cells (APCs) of the innate immune system: natural killer cells, dendritic cells (DCs), macrophages, neutrophils and CD4+ and CD8+ T cells. 20 Of all the APCs, the DCs are considered to be the most powerful.…”

IL-10 gene polymorphism and influence of chemotherapy on cytokine plasma levels in childhood acute lymphoblastic leukemia patients

“…Many studies have analyzed IL-10 polymorphisms and its expression in different models, like inflammatory, infectious, auto-immune diseases and cancer [12,13]. In cancer, these polymorphisms have been associated with increased risk in several types, including cervical [14], gastric [15], colorectal [16], B-cell lymphoma [17] and lung [18].…”

Role of IL-10 polymorphisms in susceptibility to hepatitis B virus-related hepatocellular carcinoma

“…Previous studies have reported associations between polymorphisms of this gene and the development of cancers, as well as several other diseases, including acute pancreatitis, coronary artery disease, and colorectal, gastric, oral, lung, esophageal, and breast cancers (Miteva et al, 2014;Qi et al, 2014;Hsu et al, 2015;Jia et al, 2015;Kumar et al, 2015;Vinod et al, 2015;Xu and Liu, 2015;Yang and Fa, 2015;Zhang et al, 2015b). For instance, Miteva et al (2014) reported that the IL-10 -1082A/G polymorphism has a significant impact on the development of colorectal cancer. Qi et al (2014) conducted a meta-analysis of 12 studies, finding that the -592G/A variant correlates with increased risk of gastric cancer among Asians, while Hsu et al (2015) reported that Taiwanese carriers of the -819T/C CT genotype have a 3.32-fold increased risk of oral cancer.…”