Genetic variations in DNA-repair genes (XRCC1, 3, and 7) and the susceptibility to hepatocellular carcinoma in a cohort of Egyptians.

Citation:
Enein, A. A. A., I. A. A. Khaled, M. M. Khorshied, A. O. A. El-Aziz, N. Zahran, A. M. El Saeed, H. I. Shousha, and H. A. L. A. Rahman, "Genetic variations in DNA-repair genes (XRCC1, 3, and 7) and the susceptibility to hepatocellular carcinoma in a cohort of Egyptians.", Journal of medical virology, vol. 92, pp. 3609–3616, 2020.

Abstract:

Chronic hepatitis C (CHC) is a worldwide etiology of chronic hepatic insult particularly in Egypt. DNA-repair systems are responsible for maintaining genomic integrity by countering threats posed by DNA lesions. Deficiency in the repair capacity due to genetic alterations in DNA-repair genes can lead to genomic instability and increased risk of cancer development. The present work aimed at studying the possible association between XRCC1-G28152A (rs25487), XRCC3-C18067T (rs861539), and XRCC7-G6721T (rs7003908) single nucleotide polymorphisms (SNPs) and the susceptibility to hepatocellular carcinoma (HCC) in Egyptian population. The study was conducted on 100 newly diagnosed HCC patients and 100 age- and sex-matched healthy controls. Laboratory workup revealed that all HCC patients have chronic hepatitis C viral infection. Genotyping of the studied SNPs was performed by real-time PCR. The heteromutant genotype of XRCC1 (GA) conferred an almost two-fold increased risk of HCC (OR ,  2.35; 95% CI, 1.33-4.04). Regarding XRCC7, the heteromutant (TG) genotype conferred a two-fold increased risk of HCC (OR ,  2.17; 95% CI, 1.23-3.82). Coinheritance of the polymorphic genotypes of XRCC1 and 7 was significantly higher in HCC cases than controls and was associated with an 11-fold increased risk of HCC (OR , 11.66; 95% CI,  2.77-49.13). The frequency of XRCC3 polymorphic genotypes in HCC patients was close to that of the controls.

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