Contribution of PNPLA3, GCKR, MBOAT7, NCAN, and TM6SF2 Genetic Variants to Hepatocellular Carcinoma Development in Mexican Patients

Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer with an increasing incidence worldwide. Single nucleotide polymorphisms (SNPs) may influence disease risk and serve as predictive markers. This study aimed to evaluate the association of <i>PNPLA3</i> (rs738409 and rs2294918), <i>GCKR</i> (rs780094), <i>MBOAT7</i> (rs641738), <i>NCAN</i> (rs2228603), and <i>TM6SF2</i> (rs58542926) SNPs with the risk of developing HCC in a Mexican population. A case-control study was conducted in unrelated Mexican individuals. Cases were 173 adults with biopsy-confirmed HCC and 346 were healthy controls. Genotyping was performed using TaqMan allelic discrimination assay. Logistic regression was applied to evaluate associations under codominant, dominant, and recessive inheritance models. <i>p</i>-values were corrected using the Bonferroni test (pC). Haplotype and gene-gene interaction were also analyzed. The GG homozygous of rs738409 and rs2294918 of <i>PNPLA3</i>, TT, and TC genotypes of <i>GCKR</i>, as well as the TT genotype of <i>MBOAT7</i>, were associated with a significant increased risk to HCC under different inheritance models (~Two folds in all cases). The genotypes of <i>NCAN</i> and <i>TM6SF2</i> did not show differences. The haplotype G-G of rs738409 and rs2294918 of <i>PNPLA3</i> was associated with an increased risk of HCC [OR (95% CI) = 2.2 (1.7-2.9)]. There was a significant gene-gene interaction between <i>PNPLA3</i> (rs738409), <i>GCKR</i> (rs780094), and <i>MBOAT7</i> (rs641738) (Cross-validation consistency (CVC): 10/10; Testing accuracy = 0.6084). This study demonstrates for the first time that <i>PNPLA3</i> (rs738409 and rs2294918), <i>GCKR</i> (rs780094), and <i>MBOAT7</i> (rs641738) are associated with an increased risk of developing HCC from multiple etiologies in Mexican patients.