Genetic/Environmental Factors & Cancer Treatment Revision Notes | A Level AQA Biology

1. Why Cancer Is a Genetic Disease — Even When the Environment Triggers It

Cancer kills around 166,000 people in the UK every year, yet at its core it is a disease of gene expression gone wrong. Whether the trigger is a cigarette, ultraviolet radiation, or an inherited mutation, the final common pathway is the same: the normal controls on cell division break down.

This lesson covers two intertwined spec requirements. First, you need to be able to evaluate evidence linking genetic and environmental factors to cancer. Second, you need to interpret how understanding oncogenes and tumour suppressor genes is being used to prevent, treat, and potentially cure cancer. Both skills appear regularly in AQA extended-response questions.

2. The Molecular Basis of Cancer: Proto-Oncogenes and Tumour Suppressors

Picture a car. The accelerator controls how fast the engine runs; the brakes stop it. Normal cell division works the same way. Proto-oncogenes are the accelerator — they encode proteins (such as growth factor receptors and transcription factors) that stimulate cell division when the body needs it. Tumour suppressor genes are the brakes — they encode proteins that inhibit division, repair DNA, or trigger apoptosis when something goes wrong.

A gain-of-function mutation in a proto-oncogene converts it into an oncogene. The resulting protein is either permanently active or produced in excess, so the cell receives a continuous 'divide now' signal regardless of whether the body needs new cells. A well-studied example is the RAS gene: a point mutation locks the RAS protein in its active form, stimulating continuous cell proliferation.

Tumour suppressor genes work differently. The most studied is TP53, which encodes the p53 protein. Under normal conditions, p53 detects DNA damage and either halts the cell cycle to allow repair or triggers apoptosis if the damage is irreparable. A loss-of-function mutation in both copies of TP53 (recall that most tumour suppressor genes follow Knudson's 'two-hit hypothesis') removes this checkpoint entirely.

The key distinction for the exam: oncogenes act in a dominant manner — one mutated copy is enough to drive proliferation. Tumour suppressor genes typically act in a recessive manner — both alleles must be inactivated before the brake is lost. This difference has direct implications for inheritance patterns and treatment strategies.

3. Genetic Risk Factors: Inherited Mutations and Familial Cancer

Some individuals inherit a mutated copy of a tumour suppressor gene in every cell of their body. They are born already one step along the two-hit pathway. The BRCA1 and BRCA2 genes are the clearest examples: inherited loss-of-function mutations in these genes are associated with a lifetime risk of breast cancer of around 70%, compared with roughly 12% in the general population.

Familial adenomatous polyposis (FAP) provides another example. Individuals inherit one defective copy of the APC tumour suppressor gene. The second copy is lost somatically in colon epithelial cells, leading to hundreds of polyps and a near-certain progression to colorectal cancer without intervention. The correlation between genotype and cancer risk here is extremely strong — but correlation still does not prove that the gene alone is sufficient; environmental modifiers also influence penetrance.

When evaluating genetic evidence, AQA expects you to distinguish between correlation and causation. A strong family history of cancer correlates with inherited mutations, but establishing causation requires mechanistic evidence — for example, demonstrating that the BRCA1 protein normally repairs double-strand DNA breaks, and that its absence allows mutations to accumulate.

4. Environmental Risk Factors: Evaluating the Evidence

Environmental carcinogens increase cancer risk by causing mutations in proto-oncogenes or tumour suppressor genes. The evidence base comes from epidemiological studies, animal models, and molecular studies identifying the specific mutations caused by each carcinogen.

The link between tobacco smoke and lung cancer is one of the strongest causal relationships in medicine. Epidemiological data show a dose-response relationship: the more cigarettes smoked per day and the longer the duration, the higher the risk. Molecular studies identified that benzo[a]pyrene in tobacco smoke causes specific G→T transversion mutations in TP53 — the same mutations found in lung tumour cells of smokers. This mechanistic evidence upgrades the relationship from correlation to causation.

Ultraviolet (UV) radiation provides a second well-evidenced example. UV-B causes pyrimidine dimers in DNA. If unrepaired, these produce characteristic C→T transitions in genes such as TP53. The correlation between UV exposure and melanoma incidence is supported by the observation that melanomas occur predominantly on sun-exposed skin, and that individuals with xeroderma pigmentosum — who lack nucleotide excision repair — have a dramatically elevated melanoma risk.

When interpreting data like the chart above, note the dose-response relationship: risk increases with exposure level. This pattern strengthens the causal argument because it is consistent with a biological mechanism (more carcinogen exposure → more DNA mutations). A flat or non-monotonic relationship would weaken the causal claim.

Other environmental factors with strong correlational and mechanistic evidence include: ionising radiation (X-rays, gamma rays) causing double-strand DNA breaks; certain viruses such as human papillomavirus (HPV), which encodes proteins that inactivate p53 and pRb; and aflatoxin B1 from the moulds Aspergillus flavus and Aspergillus parasiticus, which causes a specific G→T mutation in TP53 codon 249, strongly associated with hepatocellular carcinoma in regions with high dietary exposure.

5. Evaluating Evidence: Correlation, Causation, and Confounding Variables

AQA specifically asks you to evaluate evidence — this means weighing its strengths and limitations and reaching a reasoned conclusion. The key evaluative framework for cancer epidemiology involves four criteria: strength of association, dose-response relationship, mechanistic plausibility, and consistency across independent studies.

• Strength of association: a relative risk of 25 for heavy smokers (as shown in the chart) is a strong association; a relative risk of 1.1 is weak and may reflect confounding.
• Dose-response relationship: risk increasing with exposure level supports causation.
• Mechanistic plausibility: identifying the specific mutation caused by the carcinogen in the relevant gene provides molecular-level support.
• Consistency: the same association found in multiple independent populations and study designs (cohort, case-control, animal models) strengthens the causal claim.
• Confounding variables: factors correlated with both the exposure and the outcome (e.g. socioeconomic status correlating with both smoking and poor diet) can create spurious associations.

A common exam trap is to state that a correlation 'proves' causation. It does not. The tobacco-lung cancer link took decades to establish as causal precisely because confounders had to be ruled out and mechanistic evidence had to be gathered. When an exam question asks you to evaluate, always acknowledge what the data shows, identify its limitations, and state what further evidence would be needed.

6. From Mechanism to Medicine: Prevention, Treatment, and Cure

Understanding which genes are mutated in cancer — and what those mutations do — has transformed oncology. The same molecular knowledge that explains how cancer develops now underpins how we prevent, detect, and treat it.

Prevention starts with genetic screening. Individuals with a family history of breast or ovarian cancer can be tested for BRCA1/BRCA2 mutations. A positive result does not mean cancer is inevitable, but it allows informed decisions: increased surveillance (regular MRI screening), chemoprevention (drugs that reduce oestrogen signalling), or prophylactic surgery. The HPV vaccine prevents infection by the high-risk strains of HPV that inactivate p53 and pRb, directly reducing the incidence of cervical cancer — a prevention strategy rooted in understanding the molecular mechanism of viral oncogenesis.

Targeted therapies exploit specific molecular vulnerabilities created by oncogene mutations. Imatinib (Gleevec) was the first landmark example: in chronic myeloid leukaemia (CML), a chromosomal translocation creates the BCR-ABL fusion oncogene, which encodes a constitutively active tyrosine kinase. Imatinib fits precisely into the ATP-binding site of the BCR-ABL protein, blocking its activity. Because normal cells do not have BCR-ABL, the drug is highly selective, causing far fewer side effects than conventional chemotherapy.

The same principle applies to HER2-positive breast cancer. HER2 is a growth factor receptor encoded by an amplified proto-oncogene. Trastuzumab (Herceptin) is a monoclonal antibody that binds to the extracellular domain of the HER2 receptor, blocking its signalling and marking the cell for immune destruction. Patients are first tested for HER2 amplification — treatment is only offered where the target is present, illustrating the concept of personalised medicine.

Tumour suppressor gene knowledge also informs treatment. The PARP inhibitor class of drugs (e.g. olaparib) targets cancers with BRCA1/BRCA2 mutations. BRCA proteins normally repair double-strand DNA breaks by homologous recombination. PARP is involved in the detection and repair of single-strand breaks via the base excision repair pathway. When PARP is inhibited, unrepaired single-strand breaks collapse into double-strand breaks during DNA replication, which BRCA-deficient cells cannot repair via homologous recombination. In BRCA-deficient cancer cells, blocking PARP with olaparib means neither repair pathway functions — the cancer cell accumulates lethal DNA damage and dies. Normal cells, which retain functional BRCA proteins, can survive. This strategy is called synthetic lethality.

Worked example: Interpreting a Targeted Therapy Scenario

A patient's tumour is found to have an amplification of the EGFR gene (epidermal growth factor receptor), a proto-oncogene. Explain how this information could be used to select a treatment, and predict what would happen if the EGFR protein subsequently acquired a secondary mutation in its kinase domain that altered the drug-binding site.

1. EGFR amplification → overexpression of EGFR protein → constitutive growth signalling → oncogene mechanism — Amplification of a proto-oncogene is a gain-of-function change. The cell receives an excessive 'divide' signal. This is the molecular basis of the cancer in this patient.
2. EGFR inhibitors (e.g. erlotinib) block the kinase domain of EGFR, preventing downstream proliferation signals — Because normal cells express EGFR at lower levels and the drug targets the overactive protein, selectivity is achieved. The patient should be tested for EGFR amplification before prescribing — this is personalised medicine.
3. Secondary mutation in the kinase domain alters the drug-binding site → erlotinib can no longer bind effectively → drug loses efficacy — This is a common mechanism of acquired drug resistance in targeted therapy. The cancer evolves under selection pressure from the drug. A second-generation EGFR inhibitor designed to bind the mutant form may be required.
4. Resistance emergence highlights a limitation of targeted monotherapy; combination therapies or sequential drug strategies are used to reduce resistance probability — AQA evaluate questions often ask you to assess limitations. Acknowledging that targeted therapies can select for resistant clones, and suggesting how this might be managed, demonstrates higher-order analysis.

Answer: EGFR amplification identifies the patient as suitable for an EGFR inhibitor. A secondary kinase-domain mutation would alter the drug-binding site, causing acquired resistance by preventing the inhibitor from binding. This is a key limitation of targeted monotherapy.

7. Gene Therapy and Future Directions

Beyond targeted small molecules and antibodies, the molecular understanding of cancer opens the door to gene-level interventions. Restoring a functional copy of a tumour suppressor gene — or silencing an oncogene — is the theoretical goal of cancer gene therapy. In practice, delivery remains the central challenge: viral vectors must reach tumour cells specifically without triggering immune responses.

CAR-T cell therapy represents a different application of molecular knowledge. T cells are extracted from a patient, genetically engineered to express a chimeric antigen receptor (CAR) that recognises a tumour-specific surface protein, and reinfused. The engineered T cells then seek and destroy cells displaying that antigen. This approach has shown remarkable results in certain blood cancers and illustrates how understanding tumour cell surface markers — themselves often products of oncogene activity — enables highly specific immunotherapy.

8. Exam Technique: Evaluate, Interpret, and Analyse

The two spec requirements for this topic both use higher-order command words. 'Evaluate' means you must weigh evidence, acknowledge limitations, and reach a reasoned conclusion. 'Interpret' means you must extract meaning from information given to you — often a table, graph, or passage about a specific therapy — and connect it to the underlying biology.

This lesson has moved from the molecular machinery of cell division control, through the evidence base for genetic and environmental cancer risk, to the clinical applications that molecular understanding has enabled. The thread connecting all of it is the same: cancer arises when the balance between oncogene activity and tumour suppressor function is disrupted, and every prevention or treatment strategy targets some point in that disruption.