In low-risk populations of HCC including women, people aged < 60 years, subjects with normal ALT levels, and those carrying non-risk genotypes of PNPLA3 rs738409 and TM6SF2 rs58542926, we observed a J-shaped correlation between alcohol use and HCC; however, a positive dose–response correlation was found in their respective counterparts, even in those predominantly drinking wine. The gene discussed is TM6SF2; the disease is hepatocellular carcinoma.