Cancer Genetics - 16.02.26

Overview of Non-Medical Skin Cancer and Genetics

  • Introduction to non-medical skin cancer based on carcinomas.

  • Description of normal cell growth controlled by a series of genes.

Genetic Alterations

  • Genetic alterations in cell growth operate via cytotoxic gene functions.

  • The alteration occurs in only one cell within the body, although it is prevalent across various individuals.

  • Most genetic alterations are somatic mutations occurring in normal body cells rather than hereditary mutations.

    • Somatic mutations are mutations acquired during a person's lifetime that are not passed down to offspring.

  • A small percentage (~5-10%) of cancers are hereditary, with gene alterations present in all cells of the body from conception.

Types of Gene Mutations

  • Somatic Mutations: Predominantly acquired and specific to certain tissues.

    • Example: Mutations in breast tissue leading to breast cancer.

  • Hereditary Mutations: Consist of genetically altered cells present in every cell of an individual's body.

    • May derive from the parental germ line (sperm or egg).

Risk of Hereditary Cancer

  • Hereditary cancer syndromes arise when multiple family members are affected by cancer.

  • Increased risk of hereditary cancer is suggested by:

    • Early onset of cancer (e.g., bowel cancer diagnosed in one’s 40s versus the average age of 60-70).

    • Having multiple primary cancers (e.g., a person with both lung and bone cancers).

  • Characteristics of syndromes that increase likelihood of hereditary cancer:

    • Family history of cancer;

    • Occurrence of the same type of cancer in close relatives.

Genetic Testing and Screening

  • Genetic testing is focused on assessing the risk rather than performing routine testing for everyone.

  • Screening and prevention strategies might include:

    • Risk assessment based on family history.

    • Genetic counseling for at-risk families.

  • Medical follow-up is important for individuals at high risk of hereditary cancer but is different for those without increased risk.

Classification of Hereditary Cancers

  • Two major classifications:

    1. Based on the type of tumor clinically observed.

    2. Based on the type of genes altered:

    • Tumor Suppressor Genes: Normally, genes that act to slow down cell growth.

    • Oncogenes: Promote cell growth; mutations can lead to overactivity and uncontrolled cell proliferation.

    • DNA Damage Response Genes: Involved in DNA repair, critical for maintaining genomic stability.

Detailed Overview of Gene Types

  1. Tumor Suppressor Genes:

    • Function to slow down and control cell division. Both copies of a tumor suppressor gene must be inactivated to lead to uncontrolled growth.

    • Examples of alterations and their impacts:

      • Loss of Function: Requires two 'hits' or mutations for expression of cancer; often hereditary in nature.

      • Example: Retinoblastoma occurs due to inherited mutations leading to earlier onset and bilateral cancer.

  2. Oncogenes:

    • Normal roles are to promote cell division; mutations can activate them excessively leading to uncontrolled growth.

    • Only one mutation needed to activate oncogenes significantly.

  3. Genes Involved in DNA Repair:

    • Repair mechanisms correct DNA replication errors to maintain genomic integrity.

    • Faulty repair can lead to accumulation of mutations.

    • Example: Lynch Syndrome results from repair gene defects, increasing colon cancer risk.

Penetrance and Hereditary Cancer

  • Penetrance refers to the proportion of individuals with a specific genetic alteration that express the corresponding condition.

  • Incomplete penetrance exists when not all carriers of germline alterations develop cancer.

    • Example: A person with a faulty gene may never develop cancer, leading to genealogical skips in cancer prevalence.

Example Family Cascade for Hereditary Cancer

  • Visual example of a family tree to illustrate inheritance of a condition like breast cancer.

  • Symbols:

    • Squares represent males, circles represent females.

    • Horizontal lines denote mating lines; children are shown below.

Hereditary Non-Polyposis Colorectal Cancer (Lynch Syndrome)

  • Identified by lack of DNA repair, leading to instability in tumors.

  • Associated with additional cancers (e.g., endometrial cancer) and mismatch repair genes.

Clinical Implications

  • Understanding cancer genetics is crucial for developing tailored screening and prevention strategies.

  • Family dynamics and ancestry play a vital role in recognizing risk factors for hereditary cancer syndromes.

Conclusion

  • Early detection and intervention strategies are critical in managing hereditary cancer risks.

  • Genetic predispositions vary among families, demanding personalized approaches for testing and screening that consider family history and individual characteristics.