Germline Variants and Genetic Interactions of Several EMT Regulatory Genes Increase the Risk of HBV-Related Hepatocellular Carcinoma

• Published in: Frontiers in oncology 2021-06, Vol.11, p.564477-564477
• Main Authors: Liu, Wen-Xuan, Yang, Lei, Yan, Hui-Min, Yan, Li-Na, Zhang, Xiao-Lin, Ma, Ning, Tang, Long-Mei, Gao, Xia, Liu, Dian-Wu
• Format: Article
• Language: English
• Subjects: epithelial-mesenchymal transition; hepatocellular carcinoma; interaction; multifactor dimensionality reduction; Oncology; polymorphisms
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.564477

Epithelial-mesenchymal transition (EMT) plays an important role in the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We hypothesized that germline variants in the major EMT regulatory genes ( SNAIL1 , ZEB1 , ZEB2 , TWIST1 ) may influence the development of HBV-related HCC. We included 421 cases of HBsAg-positive patients with HCC, 1371 cases of HBsAg-positive subjects without HCC [patients with chronic hepatitis B (CHB) or liver cirrhosis (LC)] and 618 cases of healthy controls in the case-control study. Genotype, allele, and haplotype associations in the major EMT regulatory genes were tested. Environment-gene and gene-gene interactions were analysed using the non-parametric model-free multifactor dimensionality reduction (MDR) method. The SNAIL1 rs4647958T>C was associated with a significantly increased risk of both HCC (CT+CC vs . TT: OR =1.559; 95% confidence interval [ CI ], 1.073-2.264; P =0.020) and CHB+LC (CT+CC vs . TT: OR =1.509; 95% CI , 1.145-1.988; P =0.003). Carriers of the TWIST1 rs2285681G>C (genotypes CT+CC) had an increased risk of HCC (CG+CC vs . GG: OR =1.407; 95% CI , 1.065-1.858; P =0.016). The ZEB2 rs3806475T>C was associated with significantly increased risk of both HCC ( P recessive =0.001) and CHB+LC ( P recessive