Up-regulation of metabolic enzymes SHMT1, SHMT2 and GLDC, which catalyzes the conversion of serine to glycine (40) may result in increased glycine biosynthesis, and down-regulation of GAMT genes, using S-adenosylmethionine as the methyl donor to convert guanidinoacetate to creatine (41) may be associated with decreased creatine levels in ESCC cancer tissues. The gene discussed is SHMT2; the disease is esophageal squamous cell carcinoma.