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Cytokine. 2014 Jul;68(1):50-8. doi: 10.1016/j.cyto.2014.02.006. Epub 2014 Mar 20.

Impact of insulin-like growth factor 2, insulin-like growth factor receptor 2, insulin receptor substrate 2 genes polymorphisms on susceptibility and clinicopathological features of hepatocellular carcinoma.

Author information

  • 1Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
  • 2Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Electronic address: amalelshal@yahoo.com.
  • 3Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
  • 4Radiodiagnosis Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
  • 5Hepatobillary Surgery Department, National Liver Institute, Shebin Elkom, Egypt.

Abstract

BACKGROUND:

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. Insulin-like growth factor-2 (IGF-2) is an important autocrine and paracrine growth factor which may induce cell proliferation and inhibit cell apoptosis leading to the transformation of normal cells into malignant cells. This study aimed to evaluate the possible roles of IGF-2, insulin-like growth factor-2 receptor (IGF-2R), and insulin receptor substrate (IRS)-2 genes polymorphisms in susceptibility and clinicopathological features of HCC in Egyptian population.

MATERIALS AND METHODS:

Four hundred and twenty-six HCC patients and 334 controls were enrolled in the study. Polymorphisms of IGF-2+3580, IGF-2+3123, IGF-2R 1619, and IRS-2 1057 gene were detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum IGF-2 were determined using ELISA.

RESULTS:

Serum IGF-2 levels were significantly lower in HCC patients than in healthy controls. IGF-2+3580 AA genotype, IGF-2+3123 GG genotype or G allele, IRS-2 1057 DD genotype and D allele were significantly associated with HCC risk. The combination of IGF-2+3580 AA homozygosity and IGF-2R 1619 GG homozygosity presented a significant protective effect against HCC (OR=0.16,95% CI=0. 08-0.34, P=0. 005). Serum IGF-2 concentrations were significantly increased in HCC patients with the IGF-2+3580 AA genotype. We also observed that increased alpha-fetoprotein (AFP), Child-Pugh grade, tumor size, and number of malignant lesions were accompanied by a significant increase of serum IGF-2 mean values of in HCC patients.

CONCLUSION:

IGF-2, IGF-2R, and IRS-2 genes polymorphisms and their combinations are associated with risk of HCC.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Genes polymorphisms; Hepatocellular carcinoma; Insulin receptor substrate; Insulin-like growth factor-2; Insulin-like growth factor-2 receptor

PMID:
24656929
[PubMed - in process]
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