For betel nut-associated carcinogenesis, arecoline-induced ROS in OSCC cells could trigger downstream effectors, including heat shock protein (HSP) 27, Snail, TGM-2, early growth response (Egr)-1, transforming growth factor (TGF)-β1 and Smad3 that further enhanced tumor progression [31,32,33,34,35]; some of which could be suppressed by EGCG [33,35]. The gene discussed is SMAD3; the disease is neoplasm.