Cancer Genetics

Definition of Cancer
- Cancer is a genetic disease caused by abnormal genes.
- It involves genetic mutations that disrupt normal cell growth and multiplication.
Causes of Genetic Mutations
  - Mutations can occur:
    - Randomly during cell multiplication.
    - Due to exposure to carcinogens such as tobacco smoke, UV light, etc.
    - Through inheritance from parents.
  - Over time, accumulation of genetic changes leads to the transformation of healthy cells into cancerous ones.

A mutation allows a cell to grow without control.
Subsequent mutations can enable cancer to metastasize to other parts of the body.

Nature of Genetic Transmission
- Cancer itself is not inherited, but the mutations that increase the risk of cancer are inherited over generations.
Examples of Genes Associated with Cancer Risk
  - BRCA1/BRCA2 genes
  - RB1 gene
  - CHEK2
  - TSC1/TSC2 genes
  - PALB2

Definition of Oncogenes
- Oncogenes are mutated forms of proto-oncogenes, which are genes that normally regulate cell division, growth, and apoptosis (programmed cell death).
- When mutated, oncogenes lead to uncontrolled cell division and growth.
Analogy
- Oncogenes are likened to a gas pedal that is stuck down, causing the cell to multiply excessively.

Definition of Tumor Suppressor Genes
- These genes encode proteins that regulate cell division and function like brakes in a car.
Consequences of Mutation
- Mutations in tumor suppressor genes may lead to the absence or dysfunction of these regulating proteins, resulting in uncontrolled cell division.
Analogy
- A comparison is made to a car without brakes, illustrating the risk of unchecked growth.

Role of BRCA1/BRCA2
- Present in everyone, these are tumor suppressor genes that prevent cells from multiplying uncontrollably.
- Mutations allow for uncontrolled cell growth, increasing cancer risk, particularly in breast, ovarian, prostate, and pancreatic cancers.
Statistics
- Approximately 70% of women with a BRCA1 or BRCA2 mutation will develop breast cancer by age 80.
- About 45% of women with a BRCA1 mutation will develop ovarian cancer by age 80.

Characteristics of Family Cancer Syndromes
- These conditions are rare and individuals in these families inherit mutations in cancer-related genes.
- Cancer often develops at an earlier age compared to the general population.
Examples of Family Cancer Syndromes
  - Familial Adenomatous Polyposis (FAP):
    - Caused by mutations in the APC gene.
    - Significantly increases the risk of early colorectal cancer and other cancers.
  - Lynch Syndrome:
    - Caused by mutations in several genes including MLHL, MSH2, MSH6, PMS2, and EPCAM.
    - Associated with colon cancer, endometrial cancer, and other malignancies.

Misunderstanding Family Histories
  - Not all familial cancers are due to hereditary cancer syndromes; families often share common risk factors such as:
    - Environmental factors
    - Tobacco use
    - Alcohol consumption
    - Diet and obesity

Purpose of Genetic Testing
  - Genetic testing identifies inherited mutations that may increase the risk for certain cancers.
  - Recommended for individuals with:
    - A strong family history of specific cancers.
    - Cancer diagnosed at a young age or in unusual forms.
    - Family members who carry an inherited mutation.
Role of Genetic Counselors
- Professionals guide individuals through testing, addressing the risks, benefits, and potential drawbacks involved.

Definition of Biomarkers
- Biomarkers include genes, proteins, or other markers that provide critical insights about a person's cancer.
Testing and Application
  - Tumor cells or blood can be tested for biomarkers.
  - Each patient’s cancer may have a unique biomarker profile.
  - Biomarkers help in selecting treatment options including targeted therapies and immunotherapies.
  - Example: Specific cancers with an EGFR mutation can be treated using EGFR inhibitors, increasing the likelihood of treatment response.
  - Clinical trials often recruit patients based on specific biomarkers.

Key Roles of Genetic Testing
  - Identifying individuals at higher risk for cancer.
  - Enabling early screening for cancer detection.
  - Allowing modification of risk factors to help reduce cancer incidence.
  - Assisting in identifying optimal treatment strategies through biomarker profiling, relevant to cancers like colorectal cancer, breast cancer, lung cancer, and melanoma.