Mutation and Cancer: When DNA Goes Wrong

Welcome to one of the most vital—and often challenging—topics in biology! This chapter explores how tiny changes in your DNA, called mutations, can eventually lead to uncontrolled cell growth, or cancer. Understanding this connection is crucial not only for exams but also for appreciating the fundamental mechanisms that govern life, health, and disease. Don't worry if some terms seem complicated; we will break everything down into clear, manageable steps!

1. Understanding Gene Mutations

A gene mutation is simply a change in the base sequence of DNA. Since DNA is the instruction manual for making proteins, changing the sequence can change the protein, which can then change the organism's characteristics or function.

1.1 How Mutations Arise

Mutations can happen in two main ways:

  • Spontaneous Mutations: These occur randomly, usually due to errors during DNA replication (when DNA is copied before cell division). While DNA polymerase has proofreading abilities, mistakes still happen occasionally.
  • Induced Mutations (Mutagens): These are caused by external factors called mutagens.

    Mutagens are physical or chemical agents that significantly increase the frequency of mutations.
    Examples:
    • Physical mutagens: Ionizing radiation (X-rays, UV light).
    • Chemical mutagens: Chemicals found in tobacco smoke or environmental pollutants.
1.2 Types of Gene Mutation (Syllabus Focus)

We focus on two major types of gene mutation that involve changing the DNA base sequence:

1. Base Substitution

  • A single nucleotide base is replaced by a different base (e.g., A is swapped for G).

  • Analogy: If your instruction manual read "THE CAT ATE THE RAT", a substitution would be "THE CAR ATE THE RAT". Only one ‘letter’ (codon) changes.

2. Base Deletion

  • A single nucleotide base is removed (deleted) from the sequence.
  • This is often far more serious because DNA is read in groups of three bases (triplets/codons). Removing one base shifts the reading frame for every codon that follows the mutation. This is known as a frameshift mutation.

  • Analogy: If the original sentence was "THE CAT ATE THE RAT", deleting the first ‘C’ results in "THE ATA TET HER AT..." The rest of the message becomes gibberish.

1.3 Not All Mutations Matter (The Degenerate Code)

You might think any base change is catastrophic, but thanks to the structure of the genetic code, this isn't always true.

  • The genetic code is degenerate, meaning that most amino acids are coded for by more than one base triplet (codon).
  • Therefore, a base substitution may change the triplet (e.g., from GGU to GGC), but if both triplets code for the same amino acid (e.g., Glycine), the resulting protein sequence is unchanged. This is called a silent mutation.
  • However, if the substitution changes the amino acid (missense mutation) or turns the codon into a "stop" signal (nonsense mutation), the resulting polypeptide will be affected, potentially changing the protein's shape and function.


Quick Review: Gene Mutations

A change in the DNA base sequence.

Substitution changes one base; Deletion causes a frameshift.

Mutagens increase the risk.

The degenerate code provides a "safety net" against some substitutions.


2. Mutations and Cancer Development

Cancer is fundamentally a disease caused by the uncontrolled division of cells. This uncontrolled growth is often the result of mutations in genes that normally regulate the cell cycle (the process cells use to grow and divide).

2.1 Tumours: Benign vs. Malignant

A tumour is a mass of cells resulting from uncontrolled cell division. We classify tumours based on their severity:

  • Benign Tumours:
    • Usually slow-growing.
    • Have clear boundaries (they remain in one place, often encapsulated).
    • They are generally non-cancerous because they do not invade other tissues.
  • Malignant Tumours (Cancer):
    • Grow rapidly and often irregularly.
    • Are non-encapsulated; they invade surrounding tissues.
    • Crucially, they can spread through the blood or lymphatic system to form secondary tumours in other parts of the body. This process is called metastasis.
2.2 Cell Cycle Control: The Accelerator and Brakes

Cell division is tightly regulated by two groups of genes: proto-oncogenes and tumour suppressor genes. Think of them as the accelerator and the brakes of a car.

1. Proto-oncogenes (The Accelerator)

  • Normal function: These genes code for proteins that stimulate cell division and growth. They are responsible for making sure cells divide when they should (e.g., during repair).

2. Tumour Suppressor Genes (The Brakes)

  • Normal function: These genes code for proteins that slow down or stop cell division, repair damaged DNA, or cause cell death (apoptosis) if the damage is too severe. They act as guardians of the genome.
2.3 The Role of Mutation in Cancer

Cancer occurs when both the "accelerator" gets stuck and the "brakes" fail simultaneously.

When the Accelerator Gets Stuck (Oncogenes):

  • A mutation occurs in a proto-oncogene, converting it into a oncogene.
  • The oncogene produces too much of the stimulating protein, or a hyperactive version of it.
  • Result: The cell is constantly stimulated to divide, increasing the rate of division too quickly. (The accelerator is stuck down!)
  • Note: Oncogenes are often dominant mutations—only one copy needs to be mutated to cause the effect.

When the Brakes Fail (Mutated Tumour Suppressor Genes):

  • A mutation occurs in a tumour suppressor gene, causing it to become inactivated (it often loses its function completely).
  • The resulting protein is either non-functional or not produced at all.
  • Result: The gene can no longer slow down or stop inappropriate cell division, allowing the rate of division to increase unchecked. (The brakes are broken!)
  • Note: Tumour suppressor genes are usually recessive—both copies must be mutated for the "brake failure" to occur.


Key Takeaway: The Two Hits

A cell usually needs mutations in both proto-oncogenes (to become oncogenes) AND tumour suppressor genes to lose control completely and become cancerous.


3. Risk Factors and Treatment Strategies

While the underlying cause of cancer is mutation, the likelihood of those critical mutations occurring is influenced by various factors.

3.1 Specific Risk Factors

The syllabus requires you to understand that specific risk factors are associated with increased cancer incidence. These factors often act as mutagens or increase the rate of cell division, thereby increasing the chance of spontaneous mutation.

  • Smoking: Contains chemical mutagens that damage DNA, especially in the lungs.
  • Diet: High consumption of red and processed meats, low consumption of fibre, and obesity are linked to increased risk (e.g., bowel cancer).
  • UV Radiation: A physical mutagen that causes DNA damage, leading to skin cancer.
  • Genetic Predisposition: Inheriting faulty versions of tumour suppressor genes (like BRCA1) means the "brakes" are already partially damaged from birth, increasing lifetime risk.

Remember: The ability to analyse, interpret and evaluate data related to these risk factors and the incidence of disease is a key skill for this topic. Correlation does not always equal causation!

3.2 Cancer Treatment and the Cell Cycle

Most cancer treatments, particularly chemotherapy, target cells that are dividing rapidly. This is possible because we know cancer cells have a much faster, less regulated cell cycle than normal cells.

Cancer drugs work by exploiting the rapid division of cancer cells, often by interfering with specific stages of the cell cycle (G1, S, G2, or Mitosis).

Examples of how drugs relate to the cell cycle:

  1. DNA Replication Inhibition (S-phase): Some drugs prevent the synthesis of new nucleotides or interfere with the action of DNA polymerase, stopping DNA replication. Since cancer cells spend a lot of time replicating DNA, they are hit harder than normal cells.
  2. Spindle Fibre Formation Inhibition (Mitosis): Other drugs (called mitotic inhibitors) prevent the formation of the spindle fibres. Without these fibres, the chromosomes cannot separate correctly during anaphase of mitosis (3.2.10.2), halting cell division and causing the cancer cell to die.


Did you know? Since chemotherapy drugs cannot perfectly distinguish between rapidly dividing cancer cells and rapidly dividing healthy cells (like hair follicle cells, bone marrow cells, and gut lining cells), side effects like hair loss, anaemia, and nausea are common. This is the main limitation of traditional chemotherapy.


Final Summary: Mutation and Cancer
  • Mutations (substitutions/deletions) happen spontaneously or are caused by mutagens.
  • Cancer results from mutations that turn on cell division promoters (oncogenes) and turn off cell division suppressors (inactivated tumour suppressor genes).
  • Treatments often target the fast rate of division characteristic of cancer cells, usually by disrupting DNA replication or mitosis.