MTHFR and cancer: Metabolically, tobacco disrupts glycolysis, oxidative phosphorylation, and folate metabolism by altering cytochrome P450 family 2 subfamily A member 6 (CYP2A6), methylenetetrahydrofolate reductase (MTHFR), and hypoxia-inducible factor 1-alpha (HIF-1α) expression, resulting in insulin resistance, mitochondrial dysfunction, and lipid peroxidation, which exacerbate systemic diseases and cancer progression (Warburg effect).