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Association of insulin-like growth factor-I receptor polymorphism with colorectal cancer development

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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.

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Acknowledgments

This work was supported by Grant N: 4/2012 from the Fund for Scientific and Mobile project from Faculty of Medicine at the Trakia University, Stara Zagora, Bulgaria.

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Authors and Affiliations

  1. Department of Neurosurgery, Surgery and Urology, 2nd Surgery Clinic, University Hospital, Stara Zagora, Bulgaria

    Noyko S. Stanilov & Jovcho P. Jovchev

  2. BMI Healthcare, Winterbourne Hospital, Dorchester, Dorset, UK

    Noyko S. Stanilov

  3. Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Aremiska 11 street, Stara Zagora, Bulgaria

    Iliya A. Karakolev & Spaska A. Stanilova

  4. Oncology Center, University School of Medicine, Pleven, Bulgaria

    Tashko S. Deliysky

Authors
  1. Noyko S. Stanilov
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  2. Iliya A. Karakolev
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  3. Tashko S. Deliysky
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  4. Jovcho P. Jovchev
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  5. Spaska A. Stanilova
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Correspondence to Spaska A. Stanilova.

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Stanilov, N.S., Karakolev, I.A., Deliysky, T.S. et al. Association of insulin-like growth factor-I receptor polymorphism with colorectal cancer development. Mol Biol Rep 41, 8099–8106 (2014). https://doi.org/10.1007/s11033-014-3708-2

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  • DOI: https://doi.org/10.1007/s11033-014-3708-2

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