The TM6SF2 variant as a risk factor for hepatocellular carcinoma development in chronic liver disease patients.

Introduction: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. A non-synonymous single nucleotide polymorphism (SNP) of the transmembrane 6 superfamily member 2 (TM6SF2) gene is associated with non-alcoholic fatty liver disease. SNPs of the TM6SF2 gene play an important role in the pathogenesis of HCC in alcoholic cirrhosis, but there are limited data regarding other possible etiologies. We aimed to evaluate the role of the rs58542926 polymorphism in the development of HCC in Egyptian chronic liver disease (CLD) patients.

Material and methods: A total of 120 participants, including 40 HCC patients, 40 CLD patients, and 40 healthy controls, were selected. Real-time polymerase chain reaction (RT-PCR) was used to detect the TM6SF2 rs58542926 polymorphism.

Results: There were no significant differences among the three studied groups regarding age (p = 0.06) and gender (p = 0.75). Frequencies of the CT, TT, CT + TT genotypes and the T allele were significantly higher in HCC patients than in the CLD and control groups (p < 0.001, p = 0.005, and p < 0.001, respectively). CLD patients with the CT genotype had a significantly increased risk of HCC development (OR = 4.67, 95% CI: 1.67-12.90). Patients with the TT genotype had a significantly increased risk of HCC (OR = 9.33, 95% CI: 1.72-50.61). Moreover, the T allele was correlated with an increased risk of HCC (OR = 5.44, 95% CI: 2.09-14.17) compared to the C allele.

Conclusions: The TM6SF2 rs58542926 genotype is associated with an increased risk of HCC in the Egyptian population.