Introduction: Hepatocellular carcinoma (HCC) is an important global health problem accounting for 800,000 deaths per year. Recently, assessment of host genetics by identification of single nucleotide polymorphisms (SNPs) has shown to play a crucial role in identifying those at risk for HCC. Tolloid like protein 1 (TLL1) is one such SNP found on chromosome 4 which has been mainly shown to increase risk in hepatitis C virus (HCV)-associated HCC. However, most studies addressing its risk-association have been performed in Asian populations.
Methods: This was a cross-sectional analysis performed in Latin American individuals through the ESCALON network (www.escalon.eu). We analyzed DNA from 120 HCC patients and 293 cirrhotic controls from Argentina, Chile, Brazil, Colombia, Ecuador, and Peru for the variant rs1704200 in TLL1. The pathogenic variant of TLL1 was genotyped using TaqMan-genotyping assay. Multiple logistic regression was used to evaluate the association between TLL1 and HCC.
Results: The median age for HCC in Latin Americans was 68 years (IQR 62-72) with 59% being males. The most common cause of HCC was non-alcoholic fatty liver disease (59%) followed by alcohol-use related liver disease (27%). The proportions of individuals who developed HCC with a TLL1 pathogenic variant (AT/TT) was 18% and 26% for cirrhotics without HCC. The calculated Odds-Ratio (OR) for HCC among Latin Americans with the TLL1 variant was 0.699 (CI 0.379-1.291), suggesting non-significant decreased odds for HCC.
When examining HCV-associated HCC (11%) we found that the OR for HCV-associated HCC in Latin Americans was 2.07 (CI 0.934-4.586), suggesting a non-significant increased odds of being diagnosed with HCC in Latin Americans with the variant.
Discussion: TLL1 mutations do not seem to associate with HCC development in Latin Americans considering all cause of HCC. Preliminary results suggest that there could be an increased risk for HCC in Latin Americans with HCV infection. Our results do not express a significant value as the cohort is limited in size. Currently, a larger study is ongoing.
