Biology (16 - 18) Cancer

Genes that control cell division are affected when cancer develops Proto-oncogenes stimulate cell division Tumour suppressor genes slow down cell division The expression of these genes can be affected by: Heredity (genetic makeup) Environmental exposure to carcinogens Personal lifestyle

Proto-oncogenes: In a normal cell: Growth factors attach to receptors on cell membrane Relay proteins in the cytoplasm ‘switch on’ genes that cause DNA replication Mitosis follows DNA replication Mutation changes proto-oncogene into oncogene – cell division is affected by: Receptor proteins are permanently activated The gene codes for the production of excessive amounts of growth factors Cells divide too rapidly, resulting in a tumour.

Tumour suppressor genes: These have been linked with hereditary forms of cancer. They have the opposite role to proto-oncogenes in normal cells – they cause inhibition of cell division. In normal cells: They maintain normal rates of cell division by stopping the process after mitosis is complete Mutation causes the tumour suppressor gene to become inactive, which leads to: Cells that divide continuously Cells that are structurally and functionally different Most mutant cells die but some may form tumours.

Environmental chemicals and toxins Tobacco and tobacco smoke carcinogens Diet and alcohol Radiation e.g., UV radiation and X-rays Genetic factors Viruses

Carcinogens in tobacco smoke can cause successive, abnormal changes Connective tissue Basement membrane Ciliated columnar epithelium Basal cells Carcinogens in tobacco smoke can cause successive, abnormal changes In the normal lung, the epithelial lining of the trachea and bronchi is composed of ciliated cells

Normal Lung Tissue Basal cells multiply Mutations in basal cell proto-oncogenes and tumour suppressor genes (Ras and p53) accumulate, and these cells lose their ability to stop dividing These basal cells are now cancerous and penetrate the basement membrane; the spread (metastasis) of these mutated basal cells to other parts of the body is the cause of death (usually within 12 months)

Although smoking is by far the major risk factor for lung cancer, certain industrial substances, such as asbestos, and other environmental factors contribute The cancerous lung illustrated indicates that the patient was a smoker; deposits of tar (black areas) are visible in the tissue Various lung diseases are caused by environmental irritants. Research the incidence, types, causes and effects of the industrial disease pneumoconiosis

Ultraviolet radiation from the sun is a common radiation carcinogen that can lead to a malignant form of skin cancer called melanoma

Melanoma develops from cells in the upper epidermis of the skin called melanocytes Melanocytes produce structures called melanosomes within which the pigment melanin is located Melanin gives the skin its colour and absorbs ultraviolet light Absorption of ultraviolet light by melanin protects the DNA of skin cells from damaging radiation

Melanocytes in the deeper layers of the epidermis produce the pigment melanin (contained within melanosomes) magnify Melanocyte Melanosomes form a coating above the nuclei of skin cells – this protects the DNA from damaging radiation Processes carry melanosomes to epidermal cells Melanin in melanosomes

Skin colour is determined genetically and relates to the amount of melanin in the skin Skin colour is determined through the action of several genes and is therefore an example of polygenic inheritance Skin colour is a continuously varying trait ranging from very light to very dark Dark skin differs from fair skin in that the melanosomes (containing melanin) are larger and more evenly spread in the epidermis Pale skinned individuals are particularly susceptible to developing melanoma, especially if they live in sunny, tropical climates (higher intensities of damaging UV radiation)

Malignant skin lesions are usually characterised by rapid growth, an irregular boundary, colour variation, and a tendency to bleed and become crusty

Mutation in the CDKN2 gene on What kind of a gene is CDKN2? Some cases of malignant melanoma are familial – they tend to run in families Mutation in the CDKN2 gene on chromosome 9 is responsible for susceptibility to the familial form of melanoma CDKN2 codes for a protein called p16 that is an important regulator of the cell cycle p16 stops the cell from synthesising DNA – a precursor step for cell division When p16 is faulty (due to mutation of the CDKN2 gene), the cell does not have this necessary ‘brake’ and uncontrolled cell division occurs; a skin growth appears What kind of a gene is CDKN2?

Mutation in the CDKN2 gene on CDKN2 is a tumour suppressor gene Some cases of malignant melanoma are familial – they tend to run in families Mutation in the CDKN2 gene on chromosome 9 is responsible for susceptibility to the familial form of melanoma CDKN2 codes for a protein called p16 that is an important regulator of the cell cycle p16 stops the cell from synthesising DNA – a precursor step for cell division When p16 is faulty (due to mutation of the CDKN2 gene), the cell does not have this necessary ‘brake’ and uncontrolled cell division occurs; a skin growth appears CDKN2 is a tumour suppressor gene

Discuss the variation in cancer incidence and types in different world regions