TOPIC 1. CANCER BIOLOGY, CANCER EPIDEMIOLOGY, CANCER PREVENTION AND EARLY DETECTION
1. Definition and basic terminology
Cancer is a group of diseases characterised by uncontrolled proliferation of abnormal cells with the capacity to invade surrounding tissues and, in malignant disease, spread to distant sites (metastasis). Cancer develops through the accumulation of genetic and epigenetic alterations that disrupt normal control of cell growth, differentiation, survival and genome integrity.
Neoplasm: an abnormal mass of tissue whose growth is excessive and uncoordinated with normal tissue, and persists after the initiating stimulus has ceased.
Benign tumour: usually localised, often well circumscribed, does not invade or metastasise; may nevertheless cause harm through compression, hormone production or location.
Malignant tumour: invades adjacent tissue and may metastasise. Malignant epithelial tumours are carcinomas; mesenchymal tumours are sarcomas; haematological malignancies include leukaemias, lymphomas and plasma-cell neoplasms.
Dysplasia: disordered epithelial growth and maturation with cytological atypia; may be a precursor to carcinoma but is not synonymous with invasive cancer.
Carcinoma in situ: full-thickness epithelial atypia without invasion through the basement membrane.
Metastasis: spread of malignant cells to a non-contiguous site, establishing a secondary tumour.
2. Normal cell-cycle control and how it is lost
Normal tissues maintain a balance between cell proliferation, differentiation, senescence and apoptosis. The cell cycle includes G1 (growth), S (DNA synthesis), G2 (preparation for mitosis) and M (mitosis), with checkpoints that prevent damaged DNA from being replicated or passed to daughter cells.
Proto-oncogenes: normal genes that promote growth or survival when appropriately regulated. Activating mutations, amplification or translocations can convert them into oncogenes (e.g. RAS, MYC, EGFR, HER2). Oncogene activation is typically gain-of-function and may affect one allele.
Tumour-suppressor genes: restrain proliferation, promote repair or trigger apoptosis. Loss of function of both alleles is common (e.g. TP53, RB1, APC, PTEN).
DNA-repair genes: maintain genomic stability. Defects in mismatch repair, homologous recombination or nucleotide-excision repair increase mutation accumulation (e.g. MLH1/MSH2, BRCA1/2, XPA pathway genes).
Apoptosis regulators: malignant cells may evade programmed cell death through TP53 loss, increased anti-apoptotic BCL-2 signalling or altered death-receptor pathways.
Epigenetic changes: DNA methylation, histone modification and non-coding RNA changes can silence tumour-suppressor genes or alter gene expression without changing the DNA sequence.
3. Hallmarks and enabling characteristics of cancer
4. Multistep carcinogenesis
Carcinogenesis is a multistep process in which a normal cell acquires successive alterations that provide a growth or survival advantage. It is often described as initiation, promotion and progression, although the biology is more complex and overlapping.