Polymorphisms in the insulin like growth factor 1 and IGF binding protein 3 genes and risk of colorectal cancer.
BACKGROUND
The insulin-like growth factor1 (IGF1) pathway plays a significant role in both the normal and malignant cell growth. IGF1 binds to the IGF1 receptor and starts a signaling cascade that regulates cell proliferation, differentiation, and apoptosis. The bioavailability of IGF1 is regulated by the binding protein IGFBP3. A CA repeat polymorphism, in the IGF1 gene, which is located 969 bp upstream from the transcription start site and the rs2854744 and rs2854746 single nucleotide polymorphisms (SNPs) in the IGFBP3 gene have been associated with the serum levels of the respective proteins and colorectal cancer (CRC), but the results are inconsistent. We wanted to study if these polymorphisms or any haplotypes of the IGF1 and the IGFBP3 genes are associated with CRC.


METHODS
High linkage disequilibrium was seen in these gene regions. Therefore, the CA repeat along with two SNPs in the IGF1 gene, and rs2854744 (A-202C), rs2854746 (Ala32Gly) and two additional SNPs in the IGFBP3 gene were selected to cover the whole gene regions. A case-control study was carried out using 661 German CRC cases and 607 matched controls.


RESULTS
We did not find any association between the CA repeat length or any of the SNPs in the IGF1 and the IGFBP3 genes and the risk of CRC. Nor did the haplotypes of these genes affect the risk of CRC.


CONCLUSIONS
Our study suggests no major role of the assessed genetic variation within the IGF1 and the IGFBP3 genes in CRC risk.
Pechlivanis
Sonali
S
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Wagner
Kerstin
K
Chang-Claude
Jenny
J
Hoffmeister
Michael
M
Brenner
Hermann
H
Försti
Asta
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I