title: 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.
authors.affiliation: Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Armeiska 11 St., 6000, Stara Zagora, Bulgaria.
authors.forename: Lyuba D
authors.initials: LD
authors.lastname: Miteva
authors.forename: Noyko S
authors.initials: NS
authors.lastname: Stanilov
authors.forename: Tashko S
authors.initials: TS
authors.lastname: Deliysky
authors.forename: Spaska A
authors.initials: SA
authors.lastname: Stanilova
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D016753:Interleukin-10