The significance of Exonuclease 1 K589E polymorphism on hepatocellular carcinoma susceptibility in the Turkish population: a case-control study.

Abstract

Exonuclease 1 (Exo 1) is an important nuclease involved in mismatch repair system that contributes to maintain genomic stability, to modulate DNA recombination, and to mediate cell cycle arrest. A guanine (G)/adenine (A) common single nucleotide polymorphism at first position of codon 589 in Exo 1 gene determines a glutamic acid (Glu, E) to lysine (Lys, K) (K589E) aminoacidic substitution which may alter cancer risk by influencing the activity of Exo 1 protein. Exo 1 K589E polymorphism has been studied in various cancers, but its association with hepatocellular carcinoma (HCC) has yet to be investigated. To determine the association of the Exo 1 K589E polymorphism with the risk of HCC development in a Turkish population, a hospital-based case-control study was designed consisting of 224 subjects with HCC and 224 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the Exo 1 K589E polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. Our data shows that the Lys/Lys genotype of the Exo 1 K589E polymorphism is associated with increased risk of HCC development in this Turkish population [odds ratio (OR) = 2.15, 95% confidence interval (CI): 1.13-4.09, P = 0.02]. Furthermore, according to stratified analysis, a significant association was observed between the homozygote Lys/Lys genotype and HCC risk in the subgroups of male gender (OR = 2.67, 95% CI: 1.27-5.61, P = 0.009) and patients with non-viral-related HCC (OR = 3.14, 95% CI: 1.09-8.99, P = 0.03). Because our results suggest for the first time that the Lys/Lys homozygote genotype of Exo 1 K589E polymorphism may be a genetic susceptibility factor for HCC in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.

• Authors: Süleyman Bayram, Hikmet Akkız, Aynur Bekar, Ersin Akgöllü, Selçuk Yıldırım
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 39 Issue 5 Pg. 5943-51 (May 2012) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 22205538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• EXO1 protein, human
• Exodeoxyribonucleases
• DNA Repair Enzymes

Topics

• Adult
• Aged
• Aged, 80 and over
• Alleles
• Amino Acid Substitution (genetics)
• Carcinoma, Hepatocellular (enzymology, genetics)
• Case-Control Studies
• DNA Repair Enzymes (genetics)
• Exodeoxyribonucleases (genetics)
• Female
• Gene Frequency (genetics)
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genetics, Population
• Humans
• Liver Neoplasms (enzymology, genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Risk Factors
• Turkey
• Young Adult