1. The Genetics of Cancer

2. Newspapers, magazines, radio, and television are reporting discoveries and breakthroughs attributing one form of cancer or another to a specific gene. Cancer of the breast, colon, prostate, and many other sites in the body are being connected to specific genes... But the meaning of this isn't always clear. What does it mean for you if your mother has or had breast cancer... or an aunt and two cousins have colon cancer? What does it mean for your children if you've been diagnosed with cancer of the endocrine glands or some other organ? Cancer in the media

3. cancer is a disease of the cell cycle

4. Types of genes which may mutate to cause cancer: Tumour suppressor genes oncogenes DNA repair genes telomerase p53

5. The environment: Some environmental agents associated with cancer are: Viruses Tobacco smoke Food Radiation Chemicals Pollution

6. Viruses Viruses—mostly in the form of DNA viruses—have been causally linked to cancer. human papillomaviruses—primarily types 16 and 18, which are sexually transmitted—have been linked to cervical cancer; more than 25 other types of papillomaviruses have been linked to cancer as well hepatitis B and C—linked to cancer of the liver human immunodeficiency virus (HIV)—linked to Kaposi's sarcoma and lymphoma retroviruses—linked to cancers in animals other than humans

7. Tobacco smoke is associated with 50% to 60% of all cancer deaths is causally linked to cancers of the lung, upper respiratory tract, oesophagus, bladder, pancreas is probably a cause of cancer of the stomach, liver, kidneys, colon, and rectum

8. Food is connected to 50% to 60% of cancer deaths is causally linked to cancers of the lung, upper respiratory tract, oesophagus, bladder, pancreas is probably a cause of cancers of the stomach, liver, kidneys, colon, and rectum

9. Radiation UVB from the sun can damage DNA and is associated with more than 90% of skin cancers, including melanomas radon has been associated with lung cancer among those who work in mines; general levels of radon have not posed a significant cancer threat electric and magnetic fields from power lines and household appliances have not been demonstrated contributors to the incidence of cancer or leukaemia radio frequency electromagnetic radiation from mobile phones or microwave ovens has not been linked to cancer. nuclear radiation is of sufficient energy to ionise molecules and is therefore carcinogenic.

10. Chemicals benzene (myelogenous leukaemia) arsenic containing pesticides (lung cancer) polychlorinated biphenyls (liver and skin cancers) mineral oils (skin cancer) mineral fibres (lung cancer and mesothelioma) Chemicals, many of which have been historically linked to the workplace, have been successfully limited through public health efforts, because they have been associated with a variety of cancers. Examples of common chemicals that fall in this category are:

11. Pollution Pollution has been difficult to document as a contributor to human cancer. However, long-term exposure to high levels of air pollution may increase lung cancer risk by as much as 25%.

12. Cancer terminology Classification by tissue type: carcinoma epithelial cell 90% of all tumours derived from ectoderm (mostly) or endoderm (some) sarcoma connective tissue 2% of all tumours derived from mesoderm leukaemia circulatory or lymphatic 8% of all tumours derived from mesoderm Classification by the type of cells: Adenomatous cells ductal or glandular cells Squamous cells flat cells Myeloid blood cell Lymphoid lymphocytes or macrophages

13. Cancer terminology Classification by the site of origin of the tumour: Breast: carcinoma of ductal, medullary, papillary, etc. cells Lung: small cell, bronchioloalveolar, squamous, large cell carcinomas Bone: osteosarcoma, Ewing's sarcoma Eye: retinoblastoma Lip, tongue, mouth, nasal cavity: squamous cell carcinoma Lymphocytes: acute lymphocytic leukaemia, chronic lymphocytic leukaemia, Hodgkin's lymphoma Ovary: adenocarcinoma, choriocarcinoma, teratoma, Brenner tumour Testis: seminoma, teratocarcinoma,

14. Cancer terminology Benign tumours are generally slow growing and enclosed in a fibrous capsule are relatively innocuous, although their location can make them serious (such as a tumour located in the brain) are not considered cancerous (that is, they are not malignant) are given names that usually end in "oma" (although a melanoma is a malignant skin cancer) Malignant tumours proliferate rapidly, invading neighbouring tissues can metastasise, or spread, to other sites of the body are named using the conventions of tissue, cell type, and origin e.g. A tumour of the bone is an osteoma if benign and an osteosarcoma if malignant

15. Tumour suppressor genes The gene’s normal function is to regulate cell division. Both alleles need to be mutated or removed in order to lose the gene activity. The first mutation may be inherited or somatic. The second mutation will often be a gross event leading to loss of heterozygosity in the surrounding area.

16. Knudsen’s “two hit” hypothesis

17. retinoblastoma

18. Retinoblastoma (RB) is a malignant tumor of the developing retina that occurs in children, usually before the age of five years. All forms of retinoblastoma represent a mutation in the gene RB1 located in in the region 13q14.1-q14.2. The gene is about 180 kb in length with 27 exons that code for a transcript of only 4.7 kb. individual mutations are heterogeneous: 20% are deletions larger than 1kb; 30% are small deletions or insertions; 45% are point mutations. mutations have been found in 25 of the 27 coding exons and in promoter elements. Genotype-phenotype correlation: most mutant RB1-alleles show premature termination codons and are associated with almost complete penetrance (>95%) and high expressivity (more than 6 individual retinoblastoma foci per individual and, therefore, most often involvement of both eyes); some rare mutant alleles that code for proteins with retention of parts of the functions of the wild-type protein or that result in diminished amounts of wild- type transcript are associated with incomplete penetrance (<75%) and low expressivity (mean of less than 2 tumor foci)

19. RB1 Is regulated by phosphorylation by Cdk2 Hypophosphorylated form binds and sequesters E2F (and viral proteins such as E7 from human papilloma virus-16) It also interacts directly with the product of the ABL gene and participates in several regulatory and feed back loops even involving its own transcription.

20. Breast Cancer “Why do so many of my relatives have breast cancer...is this just plain bad luck or what?”