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Introduction. Statistics History. Origin . Word cancer Greek Hippocrates (460-370 B.C.) Carcino: non-ulcer forming Carcinoma: ulcer forming Refer to finger like spreading of disease and blood vessels which are akin to crab shape. American Cancer Society. Main Concerns. Abnormal growth

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Introduction l.jpg

Introduction

  • Statistics

  • History


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Origin

  • Word cancer

  • Greek Hippocrates (460-370 B.C.)

  • Carcino: non-ulcer forming

  • Carcinoma: ulcer forming

  • Refer to finger like spreading of disease and blood vessels which are akin to crab shape

American Cancer Society


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Main Concerns

  • Abnormal growth

  • Principal health hazard- malignant nature, invade and metastasize

  • Given advances in public health (sanitation, drugs and vaccines) infectious diseases have subsided resulting in CANCER AND HEART DISEASE AS MAJOR CAUSES OF DEATH


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General Statistics

  • Over 1 million new cancer cases expected 2003 (1,334,100)

  • In U.S.: 1/4 deaths caused by cancer

  • 1/2 American men

  • 1/3 American women

American Cancer Society


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Statistics

  • 8.9 million Americans with cancer alive 1999

  • Since 1990- 17 million new cases diagnosed

American Cancer Society


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Deaths

  • Cancer 2nd leading cause of death in U.S. (1st heart disease)

  • 556,500 Americans expected die

  • 1,500 deaths per day

American Cancer Society


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History

  • 3000-1500 B.C.

    Egyptian papyri describe breast cancer

    8 cases of tumors

    Treated by cauterization (“the fire drill”)

    Writings say that “There is no treatment”

  • 1900-1600 B.C.

    Oldest specimen cancer

    Female skull:head/neck cancer & osteosarcoma

www.rare-cancer.org/history.html

American Cancer Society


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History

  • 2400 years ago Peruvian Incas

    Malignant melanoma

  • 1932 Louis Leakey

    Found oldest hominod malignant tumor

    Remains Homo erectus or Australopithecus

    Suggestive Burkitt’s lymphoma

www.rare-cancer.org/history.html

American Cancer Society


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History of diagnosis

  • 1761 Giovanni Morgagni

    Autopsies

    Relate patient’s illness to pathogenesis

  • 1728-1793 John Hunter

    Cancer treatment via surgery

    Decide which cancers to treat

    If tumor has not invaded nearby tissue and is movable then “there is no impropriety in removing it”.

www.rare-cancer.org/history.html

American Cancer Society


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History of diagnosis

  • 19th century Rudolf Virchow

    • Founder of cellular pathology

    • Using microscopes conducted modern pathologic study

  • Tissues removed by surgeon could now be examined

    • Greater role for pathologists

    • Assist surgeons in determining whether all cancerous tissue was removed

www.rare-cancer.org/history.html

American Cancer Society


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History of diagnosis

  • 19th century Stephen Paget

    • “Seed and Soil” Theory

    • Metastic tumor cells are seed, evenly distributed throughout body

    • Seeds only grow in appropriate conditions, called soil

  • 1896 William Roentgen (German prof.)

    • Discovered x-rays

    • Used to detect and then for treatment

www.rare-cancer.org/history.html

American Cancer Society


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Finding the cause

  • Middle ages- excess black bile collecting in various body sites

  • 18th century- fermenting & degenerating lymph fluid

  • 1800s/early 1900s- trauma chronic irritation , viral and cellular deviations

www.rare-cancer.org/history.html


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Finding the cause

  • 1761- John Hill

    • Connection with use of tobacco

    • “Cautions against the Immoderate Use of Tobacco”

  • 1775- Percivall Pott

    • Occupational hazard

    • Cancer of the scrotum in chimney sweep caused by soot collection

www.rare-cancer.org/history.html


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Finding the cure

  • 2nd century Galen (Greek physician)

    • 1st oncologist

    • Galen and Hippocrates believed cancer is side effect of melancholia

    • Cancer incurable

  • 17th century Adrian Helvetius

    • Performed lumpectomy & mastectomy for breast cancer: claimed curative procedure

  • 1728-1793 John Hunter believed cancers cured by surgery

www.rare-cancer.org/history.html


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Finding the cure

  • 1880s/90s William Stewart Holsted

    • Remove breast, underlying muscle and lymph node tissue under the arm

    • Achieved 72% 5-year cure rate if disease not spread to adjoining glands

  • 1899 radiation by x-ray

  • WWI/II mustard gas

    • Exposure leads to low WBCs

    • 1940s given I.V., not inhaled

www.rare-cancer.org/history.html


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Survival

  • 62% survival for all cancers combined

  • Considerations: living 5 years post-diagnosis

    • Disease-free

    • In remission

    • Under treatment with evidence of cancer


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Costs

  • 2002 $171.6 billion

    • $60.9 billion (35%) direct medical

    • $15.5 billion (9%) indirect morbidity

    • $95.2 billion (56%) indirect mortality

  • Lack of health care for many patients

American Cancer Society


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California

  • Most new cancer cases 125,000

  • Most cancer-related deaths 52,200


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Types of Cancer

  • 11 different types of cancer= 80% of all cancers in the U.S.


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Most Frequent Types of Cancers

  • Skin 600,000

  • Lung

  • Colon/rectum

  • Breast

  • Prostate


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Change in cancer frequencies

  • Increase in lung cancer

  • Decrease in stomach, uterine cervix cancers


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Cancer Death Rates*, for Men, US, 1930-1999

Rate Per 100,000

Lung

Prostate

Stomach

Colon and rectum

Pancreas

Leukemia

Liver

*Age-adjusted to the 2000 US standard population.

Source: US Mortality Public Use Data Tapes 1960-1999, US Mortality Volumes 1930-1959,

National Center for Health Statistics, Centers for Disease Control and Prevention, 2002.


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Cancer Death Rates*, for Women, US,1930-1999

Rate Per 100,000

Lung

Uterus

Breast

Colon and rectum

Stomach

Ovary

Pancreas

*Age-adjusted to the 2000 US standard population.

Source: US Mortality Public Use Data Tapes 1960-1999, US Mortality Volumes 1930-1959,

National Center for Health Statistics, Centers for Disease Control and Prevention, 2002.


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2003 Estimated US Cancer Deaths*

Men285,900

Women270,600

Lung & bronchus31%

Prostate10%

Colon & rectum10%

Pancreas5%

Non-Hodgkin4%lymphoma

Leukemia4%

Esophagus4%

Liver/intrahepatic3%bile duct

Urinary bladder3%

Kidney3%

All other sites22%

  • 25%Lung & bronchus

  • 15%Breast

  • 11%Colon & rectum

  • 6%Pancreas

  • 5%Ovary

  • 4%Non-Hodgkin lymphoma

  • 4%Leukemia

  • 3%Uterine corpus

  • 2%Brain/ONS

  • 2%Multiple myeloma

  • 23%All other sites

ONS=Other nervous system.

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.

Source: American Cancer Society, 2003.


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Why we don’t have a cancer cure?

  • Cancer is self

  • Drugs are against rapidly dividing cells

  • Need to find unique properties of cancerous cells


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Classification

  • 2 methods to classify cancer

  • Histology: which tissue it originates

  • Primary site: location in the body

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Histology

  • Carcinoma

  • Sarcoma

  • Myeloma

  • Leukemia

  • Lymphoma

  • Mixed Types

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Carcinoma

  • Epithelium: lining of the body, skin, internal organs, 80-90% cancers

  • 2 subtypes

    • Adenocarcinoma

      • Organ/gland

      • Mucous membranes

      • At first-plaque like white mucosa

    • Squamous cell carcinoma: squamous epithelium

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Sarcoma/Myeloma

  • Sarcoma

    • Supportive/connective tissue

    • Bones, tendons, cartilage, muscle, fat

    • In young adults: painful mass

  • Myeloma

    • Plasma cells of the bone marrow

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Leukemia

  • “Liquid cancers” or “blood cancers”

  • Cancers of the bone marrow

  • Overproduction of immature white blood cells

    • Dysfunctional cells

    • Patients susceptible to infection

  • Can also impact RBCs- poor clotting, fatigue and anemia

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Lymphoma

  • “solid cancers”

  • Glands or nodes of the lymphatic system

  • Vessels, nodes, organs or lymphocytes

  • Specific organs- stomach, brain, breast

  • 2 subtypes

    • Hodgkins: contains Reed-Sternberg cells

    • Non-Hodgkins

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Primary Sites

  • Skin

  • Lung

  • Breast

  • Prostate

  • Colon and rectum

  • Uterine Corpus

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Skin

  • Basal cell, squamous cell

    • Face, ears, extremities

    • Treatable if detected and treated early

  • Melanoma

    • Melanocytes: pigment cells present in deepest layers of skin

    • More lethal due to quick metastasis

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Lung

  • Difficult to detect due to lack of symptoms

  • When disease advanced

    • Persistent cough

    • Sputum w/ blood

    • Chest pain

    • Chronic pneumonia/ bronchitis

  • Greatest increase in cancer types due to increased smoking

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Breast

  • 1 in 8 women develop disease

  • Ductal carcinoma

  • Women more likely when

    • >50 yrs age

    • Cancer in 1 breast

    • Mother/sister

    • Overweight / high fat diet

    • Early menarche/ late menopause

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Breast

  • Prevention regimens

  • Monthly breast exams

  • Most lumps not cancerous

  • Periodic mammograms after 40 yrs age

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Prostate

  • Prostate enlarge and block urethra/bladder

  • Symptoms

    • Weak/ interrupted flow

    • Urinating often

    • Difficulty urinating

    • Pain/burning, blood in urine

    • Pain in back, hips, pelvis

  • Often no symptoms

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Colon/Rectum

  • In large intestine, 70% colon, 30% rectum

  • Symptoms

    • Blood in stool

    • Constipation

    • Diarrhea

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Uterine Corpus

  • Uterus

  • Most frequently >60 yrs age

  • Symptoms: abnormal uterine bleeding

  • No/ little insight into causes

http://training.seer.cancer.gov/module_cancer

_disease/unit3_categories2_by_histology.html


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Environmental Factors

  • Lifestyle choices

  • Natural and medical radiation

  • Workplace exposures

  • Drugs

  • Substances in air, water and soil

  • Infectious diseases

http://ehp.niehs.nih.gov/roc/tenth/intro.pdf


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Carcinogens

  • Agents that cause cancer

  • Types

    1)React w/ DNA mutations alter function of regulatory genes

    2)Stimulate cell proliferation enhance initial outgrowth of cells

    3)Inhibit normal function of immune system


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Studies

  • Epidemiological studies

  • Natural experiments

  • Animal studies

  • Laboratory tests

http://www.intelihealth.com/IH/ihtIH/WSIHW000/8096/8363/185432.html?d=dmtContent


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Genetic vs. Environmental

  • Assess epidemiologic studies with target populations

  • 1st generation vs 2nd generation migratory population

    • Example Japanese in Hawaii and California whose cancer incidence went from Japanese levels to American


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10 ten environmental risks

Risk FactorLifetime Risk

1. Excessive sun exposure1 in 3

2. Cigarette smoking (one pack or + p/day) 8 in 100

3. Natural radon in indoor air at home1 in 100

4. Outside radiation1 in 1,000

5. Environmental tobacco smoke (in room with a smoker) 7 in 10,000

6. Human-made chemicals in indoor air at home2 in 10,000

7. Outdoor air in industrialized areas1 in 10,000

8. Human-made chemicals in drinking water1 in 100,000

9. Human-made chemicals in most foods (including pesticides)

1 in 100,000 or less

10. Chemical exposure at uncontrolled hazardous-waste sites

1 in 10,000 to 1,000

http://www.intelihealth.com/IH/ihtIH/WSIHW000/8096/8363/185432.html?d=dmtContent


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Classification scheme

  • Known to be carcinogen

  • Reasonably accepted to be human carcinogen

http://ehp.niehs.nih.gov/roc/tenth/intro.pdf


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http://ehp.niehs.nih.gov/roc/tenth/intro.pdf


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Tobacco

  • CIGARETTE SMOKING RESPONSIBLE FOR 1/3 OF ALL CANCER DEATHS

  • Exact carcinogen(s) in tobacco smoke unknown

  • Contributes 80-90% of lung cancers

  • Other cancers: oral cavity, pharynx, larynx, esophagus, bladder, kidney, pancreas


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Lung cancer

  • Incidence lung cancer 10x greater since 1930

    • Lag time 20 years between increase smoking and resultant increase in lung cancer

  • Impact of smoking

    • Amount of smoking

    • Years of smoking

    • Inhalation

  • Smoke cessation results in “catch-up” with non-smokers


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Alcohol

  • Excessive alcohol results increased risk

    • Oral cavity

    • Pharynx

    • Larynx

    • Esophagus

    • Liver- cirrhosis leads to excessive cell proliferation


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Synergism

  • Effects alcohol exerted in combination with smoking

    • In animals, alcohol, individually, weak carcinogen

    • Could be other ingredients, not alcohol

  • Synergism could account for many other cancers


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Radiation

  • Skin cancer common but not lethal

  • Nonmelanoma skin cancer 600,000 per year- metastasize slowly- very curable

  • Melanoma- spreads slowly

    • 27,000 cases per year

    • 6,000 deaths per year


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Radiation

  • Decay of radioactive elements

  • 80% ionizing radiation comes from natural sources  cosmic rays + radioactive substances

  • Leftover from medical sources, diagnostic x-rays


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Chernobyl

  • April 1986

  • Large cloud over Northern Europe

  • Belarus, Ukraine, Russian Federation

  • Increase childhood thyroid cancer

    • 1981-5 0.3/million

    • 1991-4 30.6/million

  • 131I in thyroid due to milk intake

  • Many more studies


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Radon

  • Radon source- decay uranium

  • Home emissions- enters from underground

  • Form small clusters with water molecules or react chemically with vapors in air

  • Enter body via inhalation

  • 3-4x more exposure than medical x-rays

  • 2nd leading carcinogen causing lung cancer

    • 10,000 lung cancer deaths per year

    • 2% total cancer mortality


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Diet

  • Dietary fat- contribute to breast and colon cancer

  • Obesity- 2-5x greater incidence of endometrial cancer in obese women- estrogen

  • Fruit and vegetables- decreased incidence

  • Fiber- possibly reduces colon cancer

  • Vitamins, cruciferous vegetables, smoked/cured/pickled foods


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Medicinal/Occupational

  • Hormones

  • Estrogens

  • Medicines contribute 1% deaths

  • Occupational exposure contributes 5%


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Environmental Pollution

  • Weak exposure

  • Only increase in cancer incidence is lung, other types of cancer not affected

  • Affects other species- fish

  • Difficult to pinpoint due to lag time


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Genetic Factors

  • Genes and environmental factors impact cancer incidence

  • Environment greater impact

  • www.cancer-genetics.org


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Inherited Cancers

  • Parent to child transmission

  • Genes inherited in dominant fashion (Mendelian genetics)

  • Inherited gene almost always leads to cancer

  • Characteristics

    • Occurs early in life

    • Lead to multiple tumors


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Genetic vrs. Sporadic Incidence

  • Many genetic factors but most sporadic (random)

  • Colon cancer

    • 2 rare genes which both contribute about 1%

    • Over 95% colon cancers represent non-inherited, sporadic disease


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Genetic Predisposition

  • Transmitted in recessive form (Mendelian genetics)

  • Requires two copies of the gene to generate disease, one from each parent

  • Not specific towards any cancer type

    • Affect stability of cellular genetic material

    • Inhibit function of the immune system


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Familial Susceptibility

Type of cancer

  • Minor overall incidence

  • Important for individual families

  • No clear explanation (hypothesis- enzymes which break down smoke toxins inhibited)


  • Xeroderma pigmentosum xp l.jpg

    Xeroderma Pigmentosum (XP)

    • Inherited DNA repair deficiency (recessive)

    • Patients suffer xtreme skin sensitivity to ultraviolet (UV) light, abnormal skin pigmentation, and high frequency of skin cancers, especially on sun-exposed skin.

    • Neurologic involvement is often part of a phenotypic spectrum

    • The worldwide frequency of XP is estimated at 1 in 250,000.


    Xp cases l.jpg

    XP cases

    Sunlight-induced dermatologic abnormalities in a patient with xeroderma pigmentosum.

    Typical skin manifestation of xeroderma pigmentosum with numerous areas of hypopigmentation and freckles (ie, solar lentigines) with different intensities of pigmentation.


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    Retinoblastoma (RB)

    • Inherited disorder (dominant), accounts for 10% of all retinoblastomas

    • Affects both eyes

    • Associated with a long-term predisposition to other types of cancer

    • 90% of all retinoblastoma cases are diagnosed within the first 3 years of the child's life


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    RB symptoms

    • 1st leukocoria, whitening of the pupil that looks like a "cat's eye“

    • Most common sign of RB- present in 60% patients


    Li fraumeni syndrome lfs l.jpg

    Li-Fraumeni Syndrome (LFS)

    • 2-4 cases/100,000 (low) 400 families worldwide

    • But, probability of tumors occurring by AGE 30 is 50% compared to normal population 1%

    • Greatly increases risk of developing several uncommon types of cancer: osteosarcoma, soft tissue sarcoma, breast cancer, brain tumors, adrenocortical carcinoma, and leukemia.


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