The Study of GGC Repeat Polymorphism in Exon 1of GSPT1/eRF3 Gene and Its Association with the Risk of Colorectal Cancer in Isfahan Region, Iran
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 exone 1 of the GSPT1/eRF3 gene suggest that this polymorphic site may play a role in cancer susceptibility.
The GGC expansion was amplified by PCR and alleles in variable size were selected by gelpolyacrylamid and sequenced directly. These sequenced alleles were used as allele specific markers.
In this research, we studies the GGC repeat polymorphism in GSPT1/eRF3 gene among 153 colorectal patients and 280 healthy controls in Isfahan region, Iran. Four different lengths of the GGC repeat in the range of 7,10,11,12 were observed. The most common genotype in controls and patients was homozygous with allele length of 10. Our primary data demonstrate that people carrying allele of 12 GGC specially 11/12 and 12/12 genotypes are at significantly higher risk of developing colorectal cancer.
A direct correlation has been found between the presence of the 12-Gly allele of this gene and development of colorectal cancer (OR = 2.66, P = 0.04). Our results also show a strong association between the allelic lengths of eRF3/GSPT1 polymorphism and family history of colorectal cancer (OR = 10.7, P = 0.0001).
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