Classify carcinogenic agents. Describe chemical, radiation and viral carcinogenesis with examples.

Classification

Chemical Carcinogenesis

Initiation — the carcinogen causes a permanent, irreversible DNA mutation in a single cell → The initiated cell is not yet a tumour and may remain dormant for years → promotion — repeated exposure to a promoter causes proliferation of the initiated clone → Promotion is reversible and does not damage DNA — a promoter alone cannot cause cancer → Order matters: initiation must come first, and promotion must be repeated and sustained → progression — further mutations, genomic instability, invasion

Radiation Carcinogenesis

• Order of tissue sensitivity — marrow and thyroid are most sensitive; bone, skin and gut least
• Latency is long — a few years for leukaemia, decades for solid tumours
• Radiologists, radium dial painters, uranium miners and the survivors of Hiroshima and Chernobyl provided the human evidence

Viral and Microbial Carcinogenesis

Host and Predisposing Factors

• Age — incidence rises steeply, reflecting accumulated mutations and declining immune surveillance
• Inherited syndromes — familial adenomatous polyposis, Li–Fraumeni, BRCA, men, retinoblastoma
• Chronic inflammation — ulcerative colitis, chronic osteomyelitis sinuses, chronic cervicitis
• Precancerous conditions — leukoplakia, Barrett oesophagus, cirrhosis, atrophic gastritis, solar keratosis
• Immunodeficiency — transplant recipients and HIV, chiefly for virus-associated tumours
• Hormones — oestrogen in endometrial and breast carcinoma

Applied Aspects

• Most cancer is preventable in principle — tobacco alone accounts for about a third, and in India tobacco chewing makes oral cancer the leading malignancy in men
• HPV vaccination prevents cervical cancer, the second commonest cancer in Indian women; hepatitis B vaccination prevents hepatocellular carcinoma
• Aflatoxin exposure is reduced by proper drying and storage of grain and groundnuts — a simple and effective intervention in India
• Occupational cancers are compensable and preventable, and asbestos remains a live problem where regulation is weak
• Sun protection reduces skin cancer; the risk is lower in pigmented skin but not absent
• Cancer is not infectious, but its causes often are — a point worth making to patients, since about one cancer in five worldwide is attributable to infection
• Latency is long for every carcinogen — usually 15 to 30 years from exposure to tumour, which is why the effect of a change in exposure is seen only a generation later
• Synergy is common — asbestos with smoking, aflatoxin with hepatitis B, alcohol with tobacco; the combined risk is far greater than the sum
• Chemoprevention — tamoxifen in high-risk breast cancer, aspirin in Lynch syndrome; effective but with their own risks
• Cancer registries track incidence and guide prevention; India’s population-based registries have documented the rise in tobacco-related cancer directly
• Occupational history should be taken in every cancer patient — it is often the only way an industrial carcinogen is identified
• The Ames test screens chemicals for mutagenicity in bacteria, and most known carcinogens are mutagens — a cheap first filter
• Not all carcinogens are mutagens — promoters such as oestrogen and phorbol esters act without damaging DNA, which is why the initiation-promotion model matters
• Removing the promoter can halt progression even after initiation has occurred, which is the biological justification for smoking cessation at any age
• Radiation is used to treat cancer and also causes it, so second malignancy is a recognised long-term risk of radiotherapy, particularly in children