What is it about?

Insulin-like growth factors (IGF) regulate growth and development and enhance cellular proliferation. IGF-binding protein-3 (IGFBP-3) inhibits IGF action by competitively binding IGFs that prevents their binding to the IGF cell surface receptor. Altered expression and serum levels of IGFBP-3 are associated with a number of malignancies. Study addressing the effect of IGFBP-3 gene polymorphism on bladder cancer is lacking. The aim of this study was to examine the effect of -202 A/C polymorphism of IGFBP-3 gene on development of bladder transitional cell carcinoma (TCC) and its correlation with serum concentration of IGF-1 and IGFBP-3 and with clinicopathological characteristics.

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Why is it important?

In the United States, bladder cancer is the fifth most common cancer in men, with an annual incidence of 18 cases per 10,000. Bladder cancer is 3 times more common in men than women. More than 90% of all bladder cancers are transitional cell carcinomas (TCC). The genetic polymorphisms in a number of genes have been shown as the modulators of bladder cancer risk. The insulin-like growth factor (IGF) system is extensively involved in human carcinogenesis. The IGF family is consisted of two peptide ligands (IGF-1 and IGF-2), two specific cell surface receptors (IGF-1R and IGF-2R), and six specific IGF-binding proteins (IGFBP-1 to IGFBP-6) (Sachdev and Yee 2007; Guvakova 2007). The mitogenic effects of IGF are mediated through interactions with IGF-1R and IGF-2R. The IGF-1R promotes motility and invasion of bladder cancer cells.


Although the IGFBP-3 gene has five SNPs, there are two reasons why we investigated this particular SNP (rs2854744). First, this SNP of IGFBP-3 gene mostly mediated the age-adjusted level of circulating IGFBP-3. Second, the most relevant single nucleotide polymorphism (rs2854744) is an A to C nucleotide change located 202 bp upstream to the transcription start site, near elements believed to control basal promoter activity of IGFBP-3.

Dr Mohammad Reza Safarinejad
University of Medical Sceices

Read the Original

This page is a summary of: The association between bladder cancer and a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) gene, Archives of Toxicology, February 2011, Springer Science + Business Media,
DOI: 10.1007/s00204-011-0671-8.
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