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Cancer – Causes and Classification Dean Bradley Who am I? • 1987-1989-Student Pharmacy Technician • BTec National Certificate in Science (pharmaceutical) • 1989-1994-Rotational Pharmacy Technician • 1994-1997-Senior Pharmacy Technician Aseptic/Cytotoxic Production • 1997-2008-Senior Pharmacy Technician Chemotherapy Day Unit • 2002-Chartered Management Institute-Diploma in Management • 2006-Postgraduate Award in Clinical Oncology • 2008-Now-Quality Manager for Haematopoietic Stem Cell Transplant Service Content • • • • • • • History of Cancer What is Cancer? Mechanism of Cancer Biological Properties of Cancer Cancer Classifications Causes of Cancer Cancer Prevention History • Cancer has afflicted humans throughout recorded history. It is no surprise that from the dawn of history people have written about cancer. • Our oldest description of cancer 1600 B.C. History • Hippocrates Greek physician (460-370 B.C.), – used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumours. In Greek these words refer to a crab. • Celsus the Roman physician, (28-50 B.C.) – later translated the Greek term into cancer, the Latin word for crab. • Galen the Roman physician (130-200 A.D.) – used the word oncos (Greek for swelling) to describe tumours. History – Causes of Cancer • • • • • • • The Gods – Ancient Egypt Humoral Theory – Hippocrates 400BC Lymph Theory – 1700’s Parasite Theory – 1700-1800’s Blastema Theory – 1830’s Chronic Irritation – 1840-1850 Trauma – late 1800’s – 1920’s Cancer is a major threat “The global burden of cancer continues to increase. In the year 2000, 5.3 million men and 4.7 million women developed a malignant tumour and 6.2 million died from the disease. The number of new cases is expected to grow by 50% over coming years to reach 15 million by 2020” Dr Gro Harlem Brundtland, Director-General, World Health Organisation, 2003 London Population 2008 = 7.2 million Cancer Incidence Figure 1.1: The 20 most commonly diagnosed cancers (ex NMSC), UK, 2005 Breast Lung Colorectal Prostate N-H-L Bladder Melanoma Stomach Oesophagus Pancreas Kidney Leukaemias Uterus Ovary Oral Brain with CNS Multiple myeloma Liver Cervix Mesothelioma Other Male 0 10,000 20,000 30,000 Number of new cases Female 40,000 50,000 What is cancer? • Is a class of diseases in which a group of cells displays: • Uncontrolled growth • Invasion • Metastasis (sometimes) What is Cancer? Malignant and Benign Mechanism of Cancer Mechanism of Cancer • DNA mutations lead to cancer • DNA mutations change protein content/activity • Gain of function mutation – Oncogenes • Loss of function mutations – Tumour suppressor genes – DNA repair genes Mechanism of Cancer • Oncogenes • Most oncogenes are mutant forms of normal proteins. • The normal gene is called a proto-oncogene Proto-oncogene c-myc c-ras c-src Oncogene myc ras src Mechanism of Cancer • Tumour Suppressor Genes • The normal proteins regulate cell division and promote DNA repair • Defects in tumour suppressor genes leads to: • Unregulated cell division • Reduced ability to repair DNA • Failure to induce apoptosis Mechanism of Cancer • DNA Repair Genes • These correct the mutations of a gene. • Mutations in DNA repair genes can lead to a failure in repair, which would allow other mutated genes to remain abnormal • BRCA1 and BRCA2 gene mutations Mechanism of Cancer • Generally cancer requires multiple mutations • Cancer is generally a stepwise process (over many years) • Requires accumulated damage to multiple genes • Activation of Oncogenes • Inactivation of tumour suppressor genes • Many cancers have more then 5 independent mutations Mechanism of Cancer Biological Properties of Cancer Cells • Acquisition of self-sufficiency in growth signals, leading to unchecked growth. • Loss of sensitivity to anti-growth signals, also leading to unchecked growth. • Loss of capacity for apoptosis, in order to allow growth despite genetic errors and external anti-growth signals. • Loss of capacity for ageing, leading to limitless replicative potential (immortality) Biological Properties of Cancer Cells • Acquisition of sustained angiogenesis, allowing the tumour to grow beyond the limitations of passive nutrient diffusion. • Acquisition of ability to invade neighbouring tissues, the defining property of invasive carcinoma. • Acquisition of ability to build metastases at distant sites, the classical property of malignant tumours (carcinomas or others). Biological Properties of Cancer Cells The completion of these multiple steps would be a very rare event without : • Loss of capacity to repair genetic errors, leading to an increased mutation rate, thus accelerating all the other changes Classification • Carcinoma • Sarcoma • Lymphoma • Leukaemia • Germ Cell • Blastoma Carcinoma • Greek: Carcinos = Crab Oma = Swelling • Originating from epithelial cells in skin or in tissues that line or cover internal organs and typically represent over 80% of diagnosed cancers Carcinoma Sarcoma • Greek: Sarx = Flesh Oma = Swelling • Originating from bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Sarcoma Lymphoma Latin: Lympha = Water, Clear water Greek:Oma = Swelling • Is a type of cancer that originates in the lymphocytes of the immune system. Lymphoma Leukaemia • Greek: Leukos = White Aima = Blood • Is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation of blood cells, usually white blood cells (leukocytes) Leukaemia Germ Cell • Latin: Germen = Sprout, bud, seed • A germ cell tumour is a cancer derived from germ cells. • Germ cells normally occur inside the gonads (Ovary and Testis). Germ cell tumours that originate outside the gonads may be birth defects resulting from errors during development of the embryo. Germ Cell Blastoma • A blastoma is a type of cancer that is caused by malignancies in precursor cells, often called blasts. Examples are nephroblastoma, medulloblastoma and retinoblastoma • Blastomas usually occur in children Blastoma Causes • Nearly all cancers are caused by mutation in the genetic material (DNA) of the transformed cells. • Substances that cause DNA mutation are known as “Mutagens” and mutagens that cause cancer are “Carcinogens” Chemical Carcinogens • • • • Over cooked food Tobacco Aflatoxin B1 Asbestos Ionizing Radiation • • • • UV Radiation (Sunshine, Sun beds) X-Rays Gamma Radiation Circadian Disruption Viral or Bacterial Infection • • • • • • Human Papillomavirus (HPV) Hepatitis B Hepatitis C Epstein-Barr Virus (EBV) Human T-Lymphotropic Virus (HTLV-1) Helicobacter pylori Hormones • • • • Oestrogen Testosterone Insulin Insulin-like growth factor 1 (IGF-1) Immune System Dysfunction • HIV • Common Variable Immune Deficiency • IgA Deficiancy Heredity • • • • • • • BRCA1 and BRCA2 Li-Fraumeni Syndrome Turcot Syndrome Familial Adenomatous Polypopsis Lynch Syndrome Retinoblastoma Down Syndrome Cancer Prevention • Modifiable Lifestyle Risk Factors – – – – – – – – – Smoking Alcohol Consumption Diet Physical Inactivity Overweight/Obese STD’s Ionizing Radiation UV Radiation Occupational and Chemical Exposure Cancer Prevention - Diet • Foods and drinks that promote weight gain: Limit • • • • • consumption of energy-dense foods; Avoid sugary drinks Plant Foods: Eat mostly foods of plant origin Animal Foods: Limit intake of red meat and avoid processed meat Alcoholic Drinks: Limit alcoholic drinks Preservation, processing, and preparation: Limit consumption of salt; Avoid mouldy cereals (grains) or pulses (legumes) Dietary supplements: Aim to meet nutritional needs through diet alone Cancer Prevention • Chemoprevention • Tamoxifen • Finasteride • COX-2 Inhibitors • Genetic testing • Vaccination • Screening • Preventative Surgery Will I get Cancer? • An individuals risk of developing cancer depends on many factors such as: – Genetic Inheritance – Smoking – Diet – Lifestyle – The environment • However, it is now clear that the cause of cancer is not due to one single event, but is multifunctional. Finally Everything in Moderation Including Moderation Harvey Steinman (food and wine critic)