The Study of GGC Repeat Polymorphism in Exon 1 of GSPT1/eRF3 Gene and its Association with the Risk of Colorectal Cancer

Document Type : Original Article (s)

Authors

1 Student, Department of Biology, School of Science, University of Isfahan, Isfahan, Iran

2 Associate Professor, Department of Biology, School of Science, University of Isfahan, Isfahan, Iran

3 Assistant Professor, Department of Radiotherapy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Laboratory Assistant, Department of Biology, School of Science, University of Isfahan, Isfahan, Iran

Abstract

Background: Colorectal cancer is the third leading cause of cancer deaths in men and the fourth in women in Iran. Eukaryotic release factor 3 (eRF3) is a GTPase associated with eRF1 in a complex that mediates translation termination in eukaryotes. Apart from its role in translation termination, the eukaryotic translation release factor 3 (eRF3) is involved in several critical cellular processes, such as cell cycle regulation and is essential for the G1 to S phase transition of the cell cycle (GSPT1), cytoskeleton organization, mRNA decay, recycle of ribosomes and apoptosis. Data from two previous studies on polymorphic GGC repeats located in exon 1 of the GSPT1/eRF3 gene suggest that this polymorphic site may play a role in cancer susceptibility.Methods: In this research, we studied the GGC repeat polymorphism in GSPT1/eRF3 gene among 153 patients with colorectal cancer and 280 healthy controls in Isfahan region, Iran. The GGC expansion was amplified via polymerase chain reaction (PCR) method and alleles in variable sizes were selected via polyacrylamide gel and sequenced directly. These sequenced alleles were used as allele specific markers.Findings: Four different lengths of the GGC repeat in the range of 7, 10, 11, and 12 were observed. The most common genotype in controls and patients was homozygous with allele length of 10. A direct correlation was found between the presence of the 12-Gly allele of this gene and development of colorectal cancer (OR = 2.66, P = 0.04). There was a strong association between the allelic lengths of eRF3/GSPT1 polymorphism and family history of colorectal cancer, too (OR = 10.7, P = 0.0001).Conclusion: Our primary data demonstrate that people carrying allele of 12 GGC, especially 11/12 and 12/12 genotypes are at significantly higher risk of developing colorectal cancer.

Keywords

References

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Journal of Isfahan Medical School
Volume 32, Issue 311 - Serial Number 311
September and October 2015
Pages 2006-2014

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History

  • Receive Date: 06 June 2014
  • Revise Date: 02 November 2024
  • Accept Date: 06 April 2022

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