As TGFβ can act as both a tumour suppressor in healthy cells and early cancer cells, but as an oncogene in later stage malignancies, the interactions between the many SMAD proteins and the TGFβ receptors is inevitably complex and mutations in the SMAD gene have been associated with metastasis in HNSCC and poorer patient outcome [44]. The gene discussed is TGFB1; the disease is cancer.