Cancer Biology Quiz

Tumour Development

• Tumours develop due to alterations or mutations in the genetic code.
• Tumour development can be influenced by both intrinsic (inherited, internal) and extrinsic (external) factors.

Intrinsic Factors

• Inheritance: Inherited conditions can predispose to tumour development related to DNA repair. Inherited susceptibility to a range of tumors can occur due to alterations in one or multiple genes.
• Host factors: Factors like age, immune status, and hormones also play a role.
  • Age: Cancer incidence increases with age.
  • Cumulative exposure to carcinogens: Repeated exposure affects risk
  • Latency: Time between exposure and manifestation
  • Accumulating genetic lesions
  • Innate defence
  • Immune factors
  • Hormones: Affect vulnerability to some cancers.

Extrinsic Factors

• Radiation: Exposure to radiation can lead to DNA damage, increasing cancer risk
  • Evidence: Skin cancer in radiologists, increased lung cancer risk in unprotected miners, and increased thyroid cancer risk in children receiving radiotherapy for head and neck (H&N) problems. Hiroshima survivors—early cases like leukemia, lymphoma; later cases like breast and thyroid cancers.
  • Mechanisms: Diverse DNA damage including single and double-stranded breaks and base damage. Dose and quality of radiation impact the outcome. Low dose: genomic instability. High dose: DNA breaks, translocation, less frequent point mutations.
• Chemicals: Carcinogenic chemicals interact with DNA, causing specific base damage and single-strand breaks. Damage may not be fully repaired, leading to mutations. Certain chemicals require metabolic conversion to become carcinogenic.
  • Types: Polycyclic aromatic hydrocarbons (e.g., coal tar, cigarette smoke, 3,4-Benzbyrene important in conversion to active form -aryl hydrocarbon hydroxylase), aromatic amines (B-naphthalamines hydroxylated to inactive form in bladder) and nitrosamines (from dietary nitrates/nitrites). Examples: lung cancer, bladder cancer, skin cancer, and gastrointestinal cancer.
• Viruses: Some viruses (e.g., Epstein Barr, Hepatitis B, Human papilloma) can cause cancer through viral oncogenes and altered DNA processes.
  • Examples: Hepatitis B and hepatocellular carcinoma; Epstein Barr and Burkitt's and Nasopharyngeal cancers; Human Papillomavirus (HPV) and cervical cancer.
• Other factors: Several other factors are involved e.g. asbestos (mesothelioma), aflatoxins (liver cancer), parasites (bladder and gastric cancers), and aspects of diet or lifestyle

Mechanisms in Carcinogenesis

• Time lag between exposure and clinical cancer.
• Stages: initiation, promotion, progression
• Initiating stimulus effects influenced by genetic factors and DNA repair.
• Promotion relies on local tissue responses and immune functions.
• Progression involves changes in gene activity and numbers leading to tumor development.
• Tumour progression is not a single alteration to one gene. It's the accumulation of alterations influenced by several factors.

Hallmarks of Cancer

• Self-sufficiency in growth signals
• Evading apoptosis
• Insensitivity to anti-growth signals
• Sustained angiogenesis
• Limitless replicative potential
• Tissue invasion and metastasis

Molecular Bases of Cancer

• Cancer is a genetic disease, characterized by altered DNA with point mutations, deletions, and translocations
• Cancer cells evade natural defense mechanisms, including DNA damage repair and apoptosis (programmed cell death).

Genes Involved

• Oncogenes: Altered proto-oncogenes present in normal cells that accelerate growth. Examples: c-myc (amplified in breast cancer and neuroblastoma), Ras (intracellular signalling mutation in colon and lung cancers), c-erbB-2 (HER-2; amplification in breast cancers).
• Tumor suppressor genes: Genes that normally restrain growth; loss of function leads to uncontrolled growth. Examples include RB gene (Retinoblastoma) and p53 (p53 mutated in >50% of cancers).
• DNA repair genes: Critical for accurate DNA replication during cell division. Defects in these genes increase the risk of accumulating mutations. Examples include BRACA1 and BRACA2 (breast cancer), and mismatch repair genes.

Objectives

• Understand inherited susceptibility to tumors.
• Understand the inheritance of certain tumors (e.g., familial adenomatous polyposis, breast cancer, retinoblastoma, ataxia telangiectasia, xeroderma pigmentosum).
• Understand the functions of oncogenes (and their alterations) and tumor suppressor genes (and their alterations). The importance of DNA repair genes
• Stages in carcinogenesis (Initiation, Promotion, Progression).
• Agents causing tumors (radiation, chemicals, viruses, hormones, parasites, etc).
• Occupations associated with tumor development.
• Medical conditions increasing tumor risk.
• Geographic variations in malignant tumor incidence.
• Host factors affecting the development of tumours.

Important Concepts:

• DNA repair mechanisms
• Genetic alterations resulting in tumor development
• Role of intrinsic and extrinsic factors in tumor development
• Mechanisms driving cancer progression.