Cancer – Causes and Classification

Cancer – Causes and Cancer – Causes and ClassificationClassification

Dean BradleyDean Bradley

Who am I?Who am I?• 1987-1989-Student Pharmacy Technician1987-1989-Student Pharmacy Technician

• BTec National Certificate in Science (pharmaceutical)BTec National Certificate in Science (pharmaceutical)

• 1989-1994-Rotational Pharmacy Technician1989-1994-Rotational Pharmacy Technician

• 1994-1997-Senior Pharmacy Technician 1994-1997-Senior Pharmacy Technician Aseptic/Cytotoxic ProductionAseptic/Cytotoxic Production

• 1997-2008-Senior Pharmacy Technician 1997-2008-Senior Pharmacy Technician Chemotherapy Day UnitChemotherapy Day Unit

• 2002-Chartered Management Institute-Diploma in Management2002-Chartered Management Institute-Diploma in Management• 2006-Postgraduate Award in Clinical Oncology2006-Postgraduate Award in Clinical Oncology

• 2008-Now-Quality Manager for Haematopoietic Stem 2008-Now-Quality Manager for Haematopoietic Stem Cell Transplant ServiceCell Transplant Service

ContentContent

• History of CancerHistory of Cancer

• What is Cancer?What is Cancer?

• Mechanism of CancerMechanism of Cancer

• Biological Properties of CancerBiological Properties of Cancer

• Cancer ClassificationsCancer Classifications

• Causes of CancerCauses of Cancer

• Cancer PreventionCancer Prevention

HistoryHistory

• Cancer has afflicted humans throughout recorded Cancer has afflicted humans throughout recorded history. It is no surprise that from the dawn of history. It is no surprise that from the dawn of history people have written about cancer. history people have written about cancer.

• Our oldest description of cancer 1600 B.C.Our oldest description of cancer 1600 B.C.

HistoryHistory

• Hippocrates Greek physician (460-370 B.C.), Hippocrates Greek physician (460-370 B.C.), – used the terms used the terms carcinoscarcinos and and carcinomacarcinoma to describe non- to describe non-

ulcer forming and ulcer-forming tumours. In Greek these ulcer forming and ulcer-forming tumours. In Greek these words refer to a crab.words refer to a crab.

• Celsus the Roman physician, (28-50 B.C.)Celsus the Roman physician, (28-50 B.C.)– later translated the Greek term into later translated the Greek term into cancercancer, the Latin , the Latin

word for crab.word for crab.

• Galen the Roman physician (130-200 A.D.)Galen the Roman physician (130-200 A.D.)– used the word used the word oncosoncos (Greek for swelling) to describe (Greek for swelling) to describe

tumours. tumours.

History – Causes of CancerHistory – Causes of Cancer

• The Gods – Ancient EgyptThe Gods – Ancient Egypt

• Humoral Theory – Hippocrates 400BCHumoral Theory – Hippocrates 400BC

• Lymph Theory – 1700’s Lymph Theory – 1700’s

• Parasite Theory – 1700-1800’sParasite Theory – 1700-1800’s

• Blastema Theory – 1830’sBlastema Theory – 1830’s

• Chronic Irritation – 1840-1850Chronic Irritation – 1840-1850

• Trauma – late 1800’s – 1920’sTrauma – late 1800’s – 1920’s

Cancer is a major threatCancer is a major threat

““The global burden of cancer continues to increase. The global burden of cancer continues to increase. In the year 2000, 5.3 million men and 4.7 million In the year 2000, 5.3 million men and 4.7 million women developed a malignant tumour and 6.2 women developed a malignant tumour and 6.2 million died from the disease. The number of new million died from the disease. The number of new cases is expected to grow by 50% over coming cases is expected to grow by 50% over coming years to reach 15 million by 2020” years to reach 15 million by 2020”

Dr Gro Harlem Brundtland, Director-General, World Health Organisation, Dr Gro Harlem Brundtland, Director-General, World Health Organisation, 20032003

London Population 2008 = 7.2 millionLondon Population 2008 = 7.2 million

Cancer IncidenceCancer Incidence

0 10,000 20,000 30,000 40,000 50,000

OtherMesothelioma

Cervix Liver

Multiple myeloma Brain with CNS

Oral Ovary

Uterus Leukaemias

Kidney Pancreas

Oesophagus Stomach

Melanoma Bladder

N-H-LProstate

Colorectal Lung

Breast

Number of new cases

Male Female

Figure 1.1: The 20 most commonly diagnosed cancers (ex NMSC), UK, 2005

What is cancer?What is cancer?

• Is a class of diseases in which a group of cells Is a class of diseases in which a group of cells displays:displays:

•Uncontrolled growthUncontrolled growth

• InvasionInvasion

•Metastasis (sometimes)Metastasis (sometimes)

What is Cancer?What is Cancer?

Malignant and BenignMalignant and Benign

Mechanism of CancerMechanism of Cancer


• DNA mutations lead to cancerDNA mutations lead to cancer

• DNA mutations change protein content/activityDNA mutations change protein content/activity

• Gain of function mutationGain of function mutation– OncogenesOncogenes

• Loss of function mutationsLoss of function mutations– Tumour suppressor genesTumour suppressor genes– DNA repair genesDNA repair genes


• OncogenesOncogenes

• Most oncogenes are mutant forms of normal proteins.Most oncogenes are mutant forms of normal proteins.

• The normal gene is called a proto-oncogeneThe normal gene is called a proto-oncogene

Proto-oncogeneProto-oncogene OncogeneOncogenec-mycc-myc mycmycc-rasc-ras rasrasc-srcc-src srcsrc


• Tumour Suppressor GenesTumour Suppressor Genes

• The normal proteins regulate cell division and The normal proteins regulate cell division and promote DNA repairpromote DNA repair

• Defects in tumour suppressor genes leads to:Defects in tumour suppressor genes leads to:

•Unregulated cell divisionUnregulated cell division

•Reduced ability to repair DNAReduced ability to repair DNA

•Failure to induce apoptosisFailure to induce apoptosis


• DNA Repair GenesDNA Repair Genes

• These correct the mutations of a gene. These correct the mutations of a gene.

• Mutations in DNA repair genes can lead to a Mutations in DNA repair genes can lead to a failure in repair, which would allow other mutated failure in repair, which would allow other mutated genes to remain abnormal genes to remain abnormal

• BRCA1 and BRCA2 gene mutationsBRCA1 and BRCA2 gene mutations


• Generally cancer requires multiple mutationsGenerally cancer requires multiple mutations

• Cancer is generally a stepwise process (over many Cancer is generally a stepwise process (over many years)years)

• Requires accumulated damage to multiple genesRequires accumulated damage to multiple genes

•Activation of OncogenesActivation of Oncogenes

• Inactivation of tumour suppressor genesInactivation of tumour suppressor genes

• Many cancers have more then 5 independent mutationsMany cancers have more then 5 independent mutations

Biological Properties of Biological Properties of Cancer CellsCancer Cells• Acquisition of self-sufficiency in growth signals, leading Acquisition of self-sufficiency in growth signals, leading

to unchecked growth. to unchecked growth.

• Loss of sensitivity to anti-growth signals, also leading Loss of sensitivity to anti-growth signals, also leading to unchecked growth. to unchecked growth.

• Loss of capacity for apoptosis, in order to allow growth Loss of capacity for apoptosis, in order to allow growth despite genetic errors and external anti-growth signals. despite genetic errors and external anti-growth signals.

• Loss of capacity for ageing, leading to limitless Loss of capacity for ageing, leading to limitless replicative potential (immortality) replicative potential (immortality)

Biological Properties of Biological Properties of Cancer CellsCancer Cells• Acquisition of sustained angiogenesis, allowing the Acquisition of sustained angiogenesis, allowing the

tumour to grow beyond the limitations of passive tumour to grow beyond the limitations of passive nutrient diffusion. nutrient diffusion.

• Acquisition of ability to invade neighbouring tissues, Acquisition of ability to invade neighbouring tissues, the defining property of invasive carcinoma. the defining property of invasive carcinoma.

• Acquisition of ability to build metastases at distant Acquisition of ability to build metastases at distant sites, the classical property of malignant tumours sites, the classical property of malignant tumours

(carcinomas or others).(carcinomas or others).

Biological Properties of Biological Properties of Cancer CellsCancer CellsThe completion of these multiple steps would be a The completion of these multiple steps would be a

very rare event without :very rare event without :

• Loss of capacity to repair genetic errors, leading Loss of capacity to repair genetic errors, leading to an increased mutation rate, thus accelerating to an increased mutation rate, thus accelerating all the other changesall the other changes

ClassificationClassification

• CarcinomaCarcinoma

• SarcomaSarcoma

• Lymphoma Lymphoma

• LeukaemiaLeukaemia

• Germ CellGerm Cell

• BlastomaBlastoma

CarcinomaCarcinoma

• Greek:Greek: Carcinos = Crab Carcinos = Crab

Oma = SwellingOma = Swelling

• Originating from epithelial cells in skin or in Originating from epithelial cells in skin or in tissues that line or cover internal organs and tissues that line or cover internal organs and typically represent over 80% of diagnosed typically represent over 80% of diagnosed cancerscancers

CarcinomaCarcinoma

SarcomaSarcoma

• Greek:Greek: Sarx = FleshSarx = Flesh

Oma = SwellingOma = Swelling

• Originating from bone, cartilage, fat, muscle, Originating from bone, cartilage, fat, muscle, blood vessels, or other connective or supportive blood vessels, or other connective or supportive tissue.tissue.

SarcomaSarcoma

LymphomaLymphoma

Latin:Latin: Lympha = Water, Clear waterLympha = Water, Clear water

Greek:Greek: Oma = SwellingOma = Swelling

• Is a type of cancer that originates in the Is a type of cancer that originates in the lymphocytes of the immune system. lymphocytes of the immune system.

LymphomaLymphoma

LeukaemiaLeukaemia

• Greek:Greek: Leukos = WhiteLeukos = White

Aima = BloodAima = Blood

• Is a cancer of the blood or bone marrow and is Is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation of characterized by an abnormal proliferation of blood cells, usually white blood cells (leukocytes) blood cells, usually white blood cells (leukocytes)

LeukaemiaLeukaemia

Germ CellGerm Cell

• Latin:Latin: Germen = Sprout, bud, seedGermen = Sprout, bud, seed

• A germ cell tumour is a cancer derived from germ A germ cell tumour is a cancer derived from germ cells.cells.

• Germ cells normally occur inside the gonads Germ cells normally occur inside the gonads (Ovary and Testis). Germ cell tumours that (Ovary and Testis). Germ cell tumours that originate outside the gonads may be birth defects originate outside the gonads may be birth defects resulting from errors during development of the resulting from errors during development of the embryo.embryo.

Germ CellGerm Cell

BlastomaBlastoma

• A blastoma is a type of cancer that is caused by A blastoma is a type of cancer that is caused by malignancies in precursor cells, often called malignancies in precursor cells, often called blasts. Examples are nephroblastoma, blasts. Examples are nephroblastoma, medulloblastoma and retinoblastomamedulloblastoma and retinoblastoma

• Blastomas usually occur in childrenBlastomas usually occur in children

BlastomaBlastoma

CausesCauses

• Nearly all cancers are caused by mutation in the Nearly all cancers are caused by mutation in the genetic material (DNA) of the transformed cells.genetic material (DNA) of the transformed cells.

• Substances that cause DNA mutation are known Substances that cause DNA mutation are known as “Mutagens” and mutagens that cause cancer as “Mutagens” and mutagens that cause cancer are “Carcinogens”are “Carcinogens”

Chemical CarcinogensChemical Carcinogens

• Over cooked foodOver cooked food

• TobaccoTobacco

• Aflatoxin BAflatoxin B11

• AsbestosAsbestos

Ionizing RadiationIonizing Radiation

• UV Radiation (Sunshine, Sun beds)UV Radiation (Sunshine, Sun beds)

• X-RaysX-Rays

• Gamma RadiationGamma Radiation

• Circadian DisruptionCircadian Disruption

Viral or Bacterial InfectionViral or Bacterial Infection

• Human Papillomavirus (HPV)Human Papillomavirus (HPV)

• Hepatitis BHepatitis B

• Hepatitis CHepatitis C

• Epstein-Barr Virus (EBV)Epstein-Barr Virus (EBV)

• Human T-Lymphotropic Virus (HTLV-1)Human T-Lymphotropic Virus (HTLV-1)

• Helicobacter pyloriHelicobacter pylori

HormonesHormones

• OestrogenOestrogen

• TestosteroneTestosterone

• InsulinInsulin

• Insulin-like growth factor 1 (IGF-1)Insulin-like growth factor 1 (IGF-1)

Immune System Immune System DysfunctionDysfunction• HIVHIV

• Common Variable Immune DeficiencyCommon Variable Immune Deficiency

• IgA DeficiancyIgA Deficiancy

HeredityHeredity

• BRCA1 and BRCA2BRCA1 and BRCA2

• Li-Fraumeni SyndromeLi-Fraumeni Syndrome

• Turcot SyndromeTurcot Syndrome

• Familial Adenomatous PolypopsisFamilial Adenomatous Polypopsis

• Lynch SyndromeLynch Syndrome

• RetinoblastomaRetinoblastoma

• Down SyndromeDown Syndrome

Cancer PreventionCancer Prevention

• Modifiable Lifestyle Risk FactorsModifiable Lifestyle Risk Factors– SmokingSmoking– Alcohol ConsumptionAlcohol Consumption– DietDiet– Physical InactivityPhysical Inactivity– Overweight/ObeseOverweight/Obese– STD’s STD’s – Ionizing RadiationIonizing Radiation– UV RadiationUV Radiation– Occupational and Chemical ExposureOccupational and Chemical Exposure

Cancer Prevention - DietCancer Prevention - Diet

• Foods and drinks that promote weight gainFoods and drinks that promote weight gain: : Limit consumption of energy-dense foods; Avoid Limit consumption of energy-dense foods; Avoid sugary drinkssugary drinks

• Plant FoodsPlant Foods: Eat mostly foods of plant origin: Eat mostly foods of plant origin• Animal FoodsAnimal Foods: Limit intake of red meat and avoid : Limit intake of red meat and avoid

processed meatprocessed meat• Alcoholic DrinksAlcoholic Drinks: Limit alcoholic drinks: Limit alcoholic drinks• Preservation, processing, and preparationPreservation, processing, and preparation: :

Limit consumption of salt; Avoid mouldy cereals Limit consumption of salt; Avoid mouldy cereals (grains) or pulses (legumes)(grains) or pulses (legumes)

• Dietary supplementsDietary supplements: Aim to meet nutritional : Aim to meet nutritional needs through diet aloneneeds through diet alone

Cancer PreventionCancer Prevention

• ChemopreventionChemoprevention

•TamoxifenTamoxifen

•FinasterideFinasteride

•COX-2 InhibitorsCOX-2 Inhibitors

• Genetic testingGenetic testing

• VaccinationVaccination

• Screening Screening

• Preventative SurgeryPreventative Surgery

Will I get Cancer?Will I get Cancer?

• An individuals risk of developing cancer depends on An individuals risk of developing cancer depends on many factors such as:many factors such as:– Genetic InheritanceGenetic Inheritance– SmokingSmoking– DietDiet– LifestyleLifestyle– The environmentThe environment

• However, it is now clear that the cause of cancer is However, it is now clear that the cause of cancer is not due to one single event, but is multifunctional.not due to one single event, but is multifunctional.

FinallyFinally

Everything in ModerationEverything in Moderation

Including ModerationIncluding Moderation

Harvey Steinman (food and wine critic)Harvey Steinman (food and wine critic)

Cancer – Causes and Classification

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