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Microsatellite polymorphism in the P1 promoter region of the IGF‑1 gene is associated with endometrial cancer

  • Authors:
    • Wojciech Kwasniewski
    • Anna Gozdzicka‑Jozefiak
    • Maria Wolun‑Cholewa
    • Grzegorz Polak
    • Jadwiga Sierocinska‑Sawa
    • Anna Kwasniewska
    • Jan Kotarski
  • View Affiliations / Copyright

    Affiliations: Department of Gynecological Oncology and Gynecology, Medical University of Lublin, Lublin 20‑081, Poland, Department of Molecular Virology, Adam Mickiewicz University, Poznan 61‑614, Poland, Department of Cell Biology, Poznan University of Medical Sciences, Poznan 60‑806, Poland, Department of Pathomorphology, University Clinical Hospital 1, Lublin 20‑081, Poland, Department of Obstetrics and Gynecology, Medical University of Lublin, Lublin 20‑081, Poland
    Copyright: © Kwasniewski et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4950-4958
    |
    Published online on: April 25, 2016
       https://doi.org/10.3892/mmr.2016.5181
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Abstract

Endometrial carcinoma (EC) is the most common type of gynecological malignancy. Studies have demonstrated that the insulin growth factor (IGF) pathway is implicated in the development of endometrial tumors and that the serum levels of IGF‑1 are affected by estrogen. Most EC cells with high microsatellite instability (MSI‑H) accumulate mutations at a microsatellite sequence in the IGF‑1 gene. The present study investigated the CA repeat polymorphism in the P1 promoter region of the IGF‑1 gene among Caucasian females with endometrial hyperplasia, EC and healthy control subjects, whose blood serum and surgical tissue specimens were analyzed. Differences or correlations between the analyzed parameters [serum levels of IGF-1 and IGF binding protein (IGFBP)‑1 and IGFBP‑3 as well as estrogens among the polymorphisms] were verified using the χ2, Mann-Whitney U, Kruskal-Wallis or Spearman’s rank correlation tests. A PCR amplification and DNA sequencing analysis was used for identification of (CA)n repeats in the P1 region of IGF‑1. ELISA was used to determine the blood serum levels of IGF‑1, IGFBP‑1, IGFBP‑3 and estrogens. Furthermore, IGF-1 was assessed in endometrial tissues by immunohistochemical analysis. The present study indicated no statistically significant differences between serum levels of IGF‑1, IGFBP‑1, IGFBP‑3 and estrone, estriol and estradiol in the control and study groups. A significant correlation was identified between the IGF-1 levels and estrone levels in the MSI-H polymorphism (r=-0.41, P=0.012) as well as a highly negative correlation between IGF-1 levels and the estradiol levels in the MSI-H polymorphism (r=-0.6, P=0.002). Genotypes without the 19 CA allele were predominantly found in EC. Furthermore, statistical analysis indicated that the number of IGF-1-expressing cells was significantly elevated in MSI-H type 18-20 (P=0.0072), MSI-L type 19-20 (P=0.025) and microsatellite-stable MSS type 19-19 (P=0.024) compared with those in the MSI-H 20-20 genotype. The present study suggested that it is rather likely that the polymorphisms in the IGF-1 promoter are associated with EC in Caucasian females with regard to its development. In the present study, polymorphisms of the IGF-1 promoter may have been introduced during the genesis of EC and contributed to it by leading to aberrant expression of IGF-1.
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Copy and paste a formatted citation
Spandidos Publications style
Kwasniewski W, Gozdzicka‑Jozefiak A, Wolun‑Cholewa M, Polak G, Sierocinska‑Sawa J, Kwasniewska A and Kotarski J: Microsatellite polymorphism in the P1 promoter region of the IGF‑1 gene is associated with endometrial cancer. Mol Med Rep 13: 4950-4958, 2016.
APA
Kwasniewski, W., Gozdzicka‑Jozefiak, A., Wolun‑Cholewa, M., Polak, G., Sierocinska‑Sawa, J., Kwasniewska, A., & Kotarski, J. (2016). Microsatellite polymorphism in the P1 promoter region of the IGF‑1 gene is associated with endometrial cancer. Molecular Medicine Reports, 13, 4950-4958. https://doi.org/10.3892/mmr.2016.5181
MLA
Kwasniewski, W., Gozdzicka‑Jozefiak, A., Wolun‑Cholewa, M., Polak, G., Sierocinska‑Sawa, J., Kwasniewska, A., Kotarski, J."Microsatellite polymorphism in the P1 promoter region of the IGF‑1 gene is associated with endometrial cancer". Molecular Medicine Reports 13.6 (2016): 4950-4958.
Chicago
Kwasniewski, W., Gozdzicka‑Jozefiak, A., Wolun‑Cholewa, M., Polak, G., Sierocinska‑Sawa, J., Kwasniewska, A., Kotarski, J."Microsatellite polymorphism in the P1 promoter region of the IGF‑1 gene is associated with endometrial cancer". Molecular Medicine Reports 13, no. 6 (2016): 4950-4958. https://doi.org/10.3892/mmr.2016.5181
Copy and paste a formatted citation
x
Spandidos Publications style
Kwasniewski W, Gozdzicka‑Jozefiak A, Wolun‑Cholewa M, Polak G, Sierocinska‑Sawa J, Kwasniewska A and Kotarski J: Microsatellite polymorphism in the P1 promoter region of the IGF‑1 gene is associated with endometrial cancer. Mol Med Rep 13: 4950-4958, 2016.
APA
Kwasniewski, W., Gozdzicka‑Jozefiak, A., Wolun‑Cholewa, M., Polak, G., Sierocinska‑Sawa, J., Kwasniewska, A., & Kotarski, J. (2016). Microsatellite polymorphism in the P1 promoter region of the IGF‑1 gene is associated with endometrial cancer. Molecular Medicine Reports, 13, 4950-4958. https://doi.org/10.3892/mmr.2016.5181
MLA
Kwasniewski, W., Gozdzicka‑Jozefiak, A., Wolun‑Cholewa, M., Polak, G., Sierocinska‑Sawa, J., Kwasniewska, A., Kotarski, J."Microsatellite polymorphism in the P1 promoter region of the IGF‑1 gene is associated with endometrial cancer". Molecular Medicine Reports 13.6 (2016): 4950-4958.
Chicago
Kwasniewski, W., Gozdzicka‑Jozefiak, A., Wolun‑Cholewa, M., Polak, G., Sierocinska‑Sawa, J., Kwasniewska, A., Kotarski, J."Microsatellite polymorphism in the P1 promoter region of the IGF‑1 gene is associated with endometrial cancer". Molecular Medicine Reports 13, no. 6 (2016): 4950-4958. https://doi.org/10.3892/mmr.2016.5181
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