Genes and Cancer

What is Cancer?

• A phenotype produced by environmental factors and an individual’s genotype.
• Cancer is a group of diseases that affect various cells and tissues.
• Two main characteristics:
  • Uncontrolled cell division: Cells divide excessively due to mutations affecting cell cycle regulation.
  • Metastasis: The ability of cancer cells to spread to other body parts.

Cancer Statistics

• Advances in medical treatments have led to improved life expectancy but also increased cancer risk.
• In Australia:
  • 1 in 2 men and 1 in 3 women will be diagnosed with cancer.
  • 30% of deaths are caused by cancer, making it a major cause of death in developed countries.

Risk Factors

• Age is the most significant risk factor. The likelihood of developing cancer increases as individuals age.
• Early diagnosis is crucial for improving treatment outcomes.

Causes of Cancer

• Various causes contribute to the development of cancer including:
  • Genetic predisposition: Certain inherited mutations and syndromes.
  • Mutagenic chemicals: Substances that cause DNA mutations.
  • Viral infections: Certain viruses are linked to specific cancers.
  • Environmental factors: Radiation, chemicals, and lifestyle choices.
  • Time: Accumulation of mutations over years leads to increased cancer risk.
• Mutation serves as the starting point for all cancers.

Types of Cancer

• Sporadic cancer: Usually the result of the accumulation of mutations over time. Environmental factors can accelerate this process.
  • Generally, more than 2 mutations are needed for sporadic cancers.
• Familial cancer: Some cancers occur in families, leading to the identification of cancer-associated genes.
  • Loss of Heterozygosity (LOH): occurs when one gene is inherited as mutated, and the normal copy mutates.

Characteristics of Cancer Type

Inheritable Susceptibilities

• Breast Cancer:
  • BRCA1 gene on chromosome 17q21.3 associated with early-onset breast cancer.
• Familial Adenomatous Polyposis (FAP):
  • Involves mutations in the APC gene (chromosome 5q22.2).
• Lynch Syndrome:
  • Related to genes like MSH2 on chromosome 2p21.

Progression of Cancer

• Cancer originates from a single cell with accumulated mutations over time.
• Cancer cells divide continuously, often changing to a more aggressive form and can invade surrounding tissues.

Types of Cancer Classification

• Carcinoma: Affects skin and tissues lining organs.
• Sarcoma: Impacts connective or supportive tissues.
• Leukemia: Affects blood and related cells.
• Lymphoma/Myeloma: Related to the immune system.
• Central Nervous System Cancer: Involves brain and spinal cord.

Cell Cycle and Cancer

• Cancer often arises from mutations that disrupt cell cycle controls.
• The cell cycle consists of:
  • G1: Cell growth before DNA replication.
  • S Phase: DNA replication occurs here.
  • G2: Further growth occurs after replication.
  • M Phase: Cell division takes place.

Cell Cycle Checkpoints

• G1/S Checkpoint: Verifies size, nutrients, growth factors, and DNA quality before entering S phase.
• G2/M Checkpoint: Ensures DNA is fully copied and repaired; apoptosis is triggered if there are errors.
• M Checkpoint: Confirms proper chromosome alignment before cell division; triggers apoptosis if errors are found.

Genes and Cancer

• Tumor-suppressor genes: Slow down cell division; mutations lead to uncontrolled growth (e.g., p53, RB1).
• Proto-oncogenes: Promote cell growth/division; mutations can result in oncogenes, leading to cancer (e.g., K-Ras).

RB1 Tumor-Suppressor Gene

• RB1 gene on chromosome 13 regulates the cell cycle; its dysfunction can lead to retinoblastoma, affecting the retina, commonly diagnosed in early childhood.

Proto-Oncogenes and Signal Transduction

• Ras family: Relay signals and regulate cell division. A mutation can lead to constitutive activation, causing excessive cell proliferation.

DNA Repair Mechanisms

• BRCA1 and BRCA2: Proteins that play critical roles in DNA repair. Mutations in these genes increase the risk of breast and ovarian cancers.
• Genomic instability: Cancers often present with structural changes in chromosomes, affecting DNA repair capabilities.

Cancer Treatment Strategies

• Traditional therapies: Chemotherapy and radiation to destroy fast-dividing cancer cells, but can harm healthy cells.
• Targeted therapies: Focus on specific genetic changes in cancer cells (e.g., Gleevec targeting BCR-ABL in CML).
• Immunotherapy: Encourages the immune system to attack cancers more effectively.

Environmental and Lifestyle Factors

• Diet, smoking, UV exposure, and viruses contribute significantly to cancer risk.
• Recommendations to lower risk include:
  • Adopt healthy eating, limit alcohol, stay physically active, and avoid tobacco.
• Vaccinations (e.g., Hepatitis B, HPV) and regular screenings can further reduce risks.

Conclusion

• Understanding cancer involves recognizing its genetic basis, environmental interactions, and cellular mechanisms.
• This knowledge aids in prevention and the development of more effective treatments.