title: Association of insulin-like growth factor-I receptor polymorphism with colorectal cancer development.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Surgery and Urology, 2nd Surgery Clinic, University Hospital, Stara Zagora, Bulgaria.
authors.forename: Noyko S
authors.initials: NS
authors.lastname: Stanilov
authors.forename: Iliya A
authors.initials: IA
authors.lastname: Karakolev
authors.forename: Tashko S
authors.initials: TS
authors.lastname: Deliysky
authors.forename: Jovcho P
authors.initials: JP
authors.lastname: Jovchev
authors.forename: Spaska A
authors.initials: SA
authors.lastname: Stanilova
mesh_terms: D000328:Adult; D000368:Aged; D002031:Bulgaria; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics*
chemical_list: C583557:IGF1 protein, human; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1