Cancer

Carcinogenesis involves alterations of genes, namely proto-oncogenes and tumor suppressor genes, which encode proteins of the signal transduction pathways that control cell division. ^[1] The cell cycle and the process of apoptosis are centrally regulated by the protein p53, and cancer arises in part from the loss of repressive signals for cell division or the loss of cell sensitivity to those signals. ^[1]

Colorectal carcinogenesis proceeds through a multistep process, classically the adenoma-carcinoma sequence described by the Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. ^[2] Cellular senescence, a permanent cell-cycle arrest, historically acts to protect against cancer, and the p53/MDM2 axis is critically involved in the regulation of aging, senescence, and oncogenesis. ^{[3] [4]} The gut microbiota can contribute to colorectal carcinogenesis, with functional studies implicating bacteria such as Fusobacterium nucleatum and certain strains of Escherichia coli and Bacteroides fragilis. ^[5]

Aging populations have a higher incidence of cancer due to lifelong exposure to cancer-causing agents, reduced DNA damage repair, accumulated genetic mutations, and decreased immune system efficiency. ^[4] Of the estimated 12.7 million cancers occurring in 2008, 610,000 (a population attributable fraction of 4.8%) could be attributed to human papillomavirus infection, with the fraction reaching 14.2% in sub-Saharan Africa. ^[6] Colorectal cancer accounts for about 10% of all new cancer cases globally, and lung cancer remains the leading cause of cancer-related deaths worldwide in both women and men. ^{[5] [7]}

The global prevalence of Helicobacter pylori infection, the major risk factor for gastric cancer, has declined over the last three decades in adults, and gastric cancer incidence has decreased globally where H. pylori prevalence has fallen. ^{[8] [9]} Smoking is the most common risk factor for urothelial bladder cancer and accounts for approximately half of all cases, underscoring the importance of primary prevention. ^[10] Cancer cachexia, an ongoing loss of skeletal muscle mass, is common in advanced cancer, and its agreed diagnostic criterion is weight loss greater than 5%, or greater than 2% in individuals already depleted (body-mass index below 20 kg/m2 or sarcopenia). ^[11]