carcinogenesis

Carcinogenesis is the process by which normal cells transform into cancer cells, typically through multiple sequential stages that accumulate genetic and epigenetic changes. The classic model divides carcinogenesis into initiation, promotion, and progression, while a modern view emphasizes clonal evolution and increasing genomic instability. Initiation involves irreversible DNA damage in a cell, often by mutagens, leading to a mutated clone that can be expanded during promotion, when growth advantage is conferred by proliferative signals or inflammatory stimuli. Progression reflects further genetic alterations that enable malignant behavior, such as invasion and metastasis.

Carcinogens are diverse: chemical agents (tobacco-related components, industrial chemicals, nitrosamines, polycyclic aromatic hydrocarbons), physical agents (ionizing radiation, ultraviolet light), and certain biological factors (high-risk oncogenic viruses such as human papillomavirus, hepatitis B and C viruses, Epstein-Barr virus). Many chemical carcinogens require metabolic activation to form DNA adducts and mutations. DNA repair defects, replication errors, and genomic instability contribute to the accumulating mutations characteristic of cancer cells. Epigenetic changes also play a role, altering gene expression without changing DNA sequence.

Genetic alterations common in carcinogenesis include activation of oncogenes (e.g., RAS, MYC) and inactivation of tumor suppressor genes (e.g., TP53, RB1) and DNA repair genes (e.g., BRCA1/2). The resultant cancer cells often display hallmarks such as sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, angiogenesis, and invasion/metastasis, along with immune evasion and metabolic reprogramming.

Epidemiology and prevention: incidence is influenced by exposure, genetic predisposition, and lifestyle. Risk reduction involves avoidance of known carcinogens, vaccination against oncogenic viruses, screening for early detection, and public health measures to reduce exposure and inflammation.