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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.

The insulin-like growth factor (IGF) system plays a prominent role in the cancer development. The IGF-1 receptor (IGF-1R) and its associated signalling pathway is an important growth regulatory pathway that has been implicated in colorectal carcinogenesis. This study was designed to compare +3179G/A IGF1R (rs 2229765) genotype distribution in 110 colorectal cancer (CRC) patients to a group of 143 healthy controls (HCs). We also investigated serum IGF-1 levels in CRC patients and HCs in an association to genotype. IGF-1 serum levels were measured by enzyme-linked immunosorbent assay and genotyping for the +3179G/A polymorphism was performed by restriction fragment length polymorphisms-polymerase chain reaction assay. Although the genotype frequencies were comparable in both groups, higher frequency of dominant genotypes [AA/AG; 71 vs. 62 %; odds ratio (OR) = 1.52] and lower frequency of GG genotype (29 vs. 38 %) was seen in cases versus controls. When CRC patient's group was divided into stages of disease by tumor-node-metastasis classification we observed the significantly highest frequency of AA genotype in III stage compared to controls: 22.5 versus 15 %; OR = 3.37, p = 0.026. There was a significant association between IGF-1R rs2229765 polymorphism and advanced CRC (AA/AG vs. GG: OR = 3.06, p = 0.004). The frequency of A-allele in advanced CRC was significantly higher then early CRC (52 vs. 37.7, OR = 1.78). According to genotype serum IGF-1 levels was significantly decreased in patients with GG genotype then patients with dominant genotypes. Our results showed a relationship between the +3179G>A polymorphism of the IGF-1R and serum IGF-1 with the progression of colorectal carcinoma. A dominant genetic model was established for IGF-1R rs2229765 polymorphism and CRC progression.

The present study investigates the association between IL12Bpro and +16974A/C in 3' -untranslated region (UTR) polymorphisms of IL12B and IL-12p40 serum level related to development of colorectal cancer (CRC). Our results showed similar distribution of both the investigated polymorphisms among CRC patients and healthy donors, which suggests that these polymorphisms in IL12B were not associated with the development of CRC. However, we found an increased IL-12p40 level in sera from patients compared to healthy donors and the highest level was observed in stage I compared to more advanced stages of CRC. These findings demonstrated that IL-12p40 serum level has an association with the progression of CRC.

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