Carcinogenesis

Key points

• • Cancer arises from a stepwise accumulation of genetic and epigenetic changes in a single cell that give it a growth advantage, so tumours are said to be clonal (grown from one ancestor cell).
• • Oncogenes are altered forms of normal growth-promoting genes (proto-oncogenes); a single overactive copy pushes the cell to divide, like a stuck accelerator (for example RAS and MYC).
• • Tumour suppressor genes normally restrain growth, and usually both copies must be lost before control fails, like failed brakes (for example TP53 and RB).
• • TP53, the guardian of the genome, normally halts the cell cycle to allow repair or triggers apoptosis, and it is one of the most commonly mutated genes in human cancers.
• • Genes that repair DNA form a third group, and losing them raises the mutation rate and speeds the appearance of the other changes.
• • Carcinogens that trigger these mutations include chemicals such as tobacco smoke, radiation such as ultraviolet light, and certain viruses such as human papillomavirus.