Define cancer. Describe in detail the effects of cancer-related genes on cell growth.

Defining Cancer

Cancer is fundamentally a genetic disease. It develops when the normal mechanisms controlling cell growth and division break down, resulting in the formation of tumors. These tumors can be benign (non-cancerous) or malignant (cancerous). Malignant tumors have the ability to invade surrounding tissues and metastasize to distant sites.

Effects of Cancer-Related Genes on Cell Growth

Cancer development is driven by alterations in three main classes of genes: oncogenes, tumor suppressor genes, and DNA repair genes. These genes regulate critical cellular processes, and their dysfunction contributes to the hallmarks of cancer.

1. Oncogenes

Oncogenes are genes that, when mutated or overexpressed, promote uncontrolled cell growth and division. They are often derived from normal genes called proto-oncogenes, which play essential roles in cell signaling and growth regulation. Activation of oncogenes can occur through various mechanisms, including point mutations, gene amplification, chromosomal translocations, and viral insertion.

• Mechanism: Proto-oncogenes become oncogenes through gain-of-function mutations. This means the mutated gene product exhibits increased activity or is produced in excessive amounts.
• Examples:
  • RAS family (KRAS, NRAS, HRAS): Frequently mutated in lung, colon, and pancreatic cancers. Mutations lead to constitutive activation of the RAS signaling pathway, promoting cell proliferation.
  • MYC: A transcription factor often amplified in Burkitt lymphoma and other cancers. Overexpression of MYC drives cell cycle progression and growth.
  • ERBB2 (HER2): Amplified in approximately 20% of breast cancers. HER2 overexpression leads to increased cell proliferation and survival.

2. Tumor Suppressor Genes

Tumor suppressor genes normally inhibit cell growth and division, repair DNA mistakes, or initiate programmed cell death (apoptosis). Loss of function mutations in these genes remove critical brakes on cell proliferation, allowing cells to grow uncontrollably.

• Mechanism: Tumor suppressor genes typically require both alleles to be inactivated for their function to be completely lost (Knudson’s “two-hit” hypothesis).
• Examples:
  • TP53: The “guardian of the genome,” mutated in over 50% of all human cancers. TP53 regulates cell cycle arrest, DNA repair, and apoptosis.
  • RB1: Mutated in retinoblastoma and other cancers. RB1 controls the G1/S transition in the cell cycle, preventing uncontrolled proliferation.
  • BRCA1/BRCA2: Involved in DNA repair. Mutations increase the risk of breast, ovarian, and other cancers.

3. DNA Repair Genes

DNA repair genes are responsible for correcting errors that occur during DNA replication and preventing the accumulation of mutations. Defects in these genes lead to genomic instability, increasing the likelihood of mutations in oncogenes and tumor suppressor genes.

• Mechanism: Mutations in DNA repair genes result in an increased mutation rate, accelerating cancer development.
• Examples:
  • MLH1, MSH2, MSH6, PMS2: Involved in mismatch repair. Mutations lead to microsatellite instability and increased risk of colorectal cancer.
  • ATM: Involved in DNA damage response. Mutations increase sensitivity to ionizing radiation and risk of leukemia and lymphoma.

Gene Interactions and Cancer Development

Cancer development is rarely caused by a single gene mutation. It typically requires the accumulation of multiple genetic alterations over time. These alterations can involve oncogene activation, tumor suppressor gene inactivation, and DNA repair gene defects. The specific combination of mutations varies depending on the type of cancer.

Gene Type	Effect on Cell Growth	Mutation Type	Example
Oncogene	Promotes uncontrolled growth	Gain-of-function	KRAS
Tumor Suppressor Gene	Inhibits growth; loss of function leads to uncontrolled growth	Loss-of-function	TP53
DNA Repair Gene	Maintains genomic stability; defects increase mutation rate	Loss-of-function	BRCA1