Lecture: Cancer and Environment - Part 2

Key Genes Associated with Cancer

1. Proto-Oncogenes

   • Normal genes that can mutate into oncogenes.
   • Promote cell growth and division.
   • Mutated proto-oncogenes (oncogenes) are stuck in "on" position.
   • Examples of proto-oncogenes:
     • Growth factors like sis
     • Growth factor receptors like HER2/neu
     • Signal transduction and transcription factors

2. Tumor Suppressor Genes

   • Regulate cell growth and apoptosis.
   • Require mutations in both alleles (two-hit hypothesis) to become non-functional.
   • Examples:
     • TP53 gene: Produces p53 protein, known as "guardian of the genome."
     • BRCA1 and BRCA2: Linked to breast and ovarian cancers.

3. DNA Repair Genes

   • Fix errors during cell division.
   • Mutations lead to accumulation of errors and increased cancer risk.
   • Example: Xeroderma pigmentosum - disorder in DNA repair caused by UV light.

DNA Structure and Function

• DNA consists of exons (coding regions) and introns (non-coding regions).
• Exons are transcribed into mRNA, introns are spliced out.
• mRNA translates into proteins.

Cell Cycle Checkpoints

• G1 Checkpoint:
  • Checks for nutrients, growth factors, DNA damage.
  • Cells in G0 are resting, not dividing.
• G2 Checkpoint:
  • Ensures cell size and DNA replication accuracy before mitosis.
• Mitosis/Meiosis:
  • Final division phase where cells split.

Mechanism of Carcinogenesis

• Multi-step Carcinogenesis Theory:
  • Multiple mutations needed for cancer development.
  • Steps include: Initiation, Promotion (Proliferation), Progression.

1. Initiation

   • Permanent mutation in cancer-related genes.
   • Examples: UV light, ionizing radiation, chemical mutagens.

2. Promotion

   • Clonal expansion of mutated cells.
   • Requires repeated exposure to promoters.

3. Progression

   • Further mutations lead to loss of control and malignancy.

Proto-Oncogene and Tumor Suppressor Gene Analogy

• Proto-Oncogene: Gas pedal in a car.
• Tumor Suppressor Gene: Brakes in a car.
  • Proto-oncogenes require one-hit mutation to become oncogenes.
  • Tumor suppressor genes require two-hit mutations for dysfunction.

Epigenetics in Cancer

• Epigenetics: Study of heritable changes not involving DNA sequence.
• Involves DNA methylation and histone modification.
• Can influence gene expression and cancer risk.

Examples of Carcinogens

• Aflatoxin, arsenic, asbestos, benzene.
• Some are mutagens, some are not.

Study Recommendations

• Review lecture material and videos.
• Understand key differences between proto-oncogenes and tumor suppressor genes.
• Familiarize with DNA repair mechanisms and their importance.
• Explore the role of epigenetics in cancer development.