Human Biology III Oncology I

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Human Biology IIIOncology I

• Ken Bauer
• kbauer_at_rx.umaryland.edu

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Objectives

• Following the lecture the student should be able
  to
• 1. Differentiate between the characteristics
  of benign and malignant tumors.
• 2. List the 5 broad categories of cancer
  etiology
• 3. Describe the effect cigarette smoking has
  had on cancer incidence and death rates from
  1930 to present.

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Objectives

• 4. Explain the roles of oncogenes
  proro-oncogenes, and tumor suppressor genes
  in the malignant transformation .
• 5. List the 3 most common tumor types in
  men and women by gender

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Cancer Terminology

• Cancer is a disorder that occurs at a cellular
  level
• Cancer occurs when genetic alterations result in
  the unregulated proliferation of cells

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Cancer Terminology

• Cancer - A group of diseases
• Anaplasia - Lack of differentiation
• Dysplasia - Abnormal size, shape
• Hyperplasia - Increase in number of cells

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Benign Tumor

• Characteristics typical of tissue of origin
• Slow rate of growth
• Slowly progressive Not fatal if untreated
• Encapsulated growth
• No tissue destruction
• Rare recurrence
• Poor prognosis only if unable to remove

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Malignant Tumor

• Characteristics atypical of tissue of origin
• Slow or rapid rate of growth
• Usually progressive Fatal if untreated
• Growth by infiltration or metastasis
• Tissue destruction is common
• Recurrence is common
• Fatal prognosis if uncontrolled

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2000 Estimated Cancer Statistics

• 1,220,100 Estimated number of new cancer cases.
• Over 100 types of cancer most common -gt
• Women Breast, Lung, Colon
• Men Prostate, Lung , Colon
• 552,200 Estimated number of cancer deaths.
• Lung cancer is leading cause of cancer deaths.
• Source American Cancer Society, www.cancer.org

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Cancer Statistics

• From 1930 until 1989 there was a steady overall
  rise in the age-adjusted death rate due to cancer
• Since 1989 the mortality trend is downward
• Major cause of increase over 60 years was
  increasing tobacco use and lung cancer
• The current trend down is due at least in part to
  decreased tobacco use

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Leading Sites of New Cancer Cases and Deaths2000
Estimates
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Age-Adjusted Cancer Death Rates, Females by
Site, US, 1930-1996
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Age-Adjusted Cancer Death Rates, Males by Site,
US, 1930-1996
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Etiology of Cancer

• The most common way of treating cancer today is
  to treat after detection
• Ideal strategy is prevention
• eliminate/reduce controllable risk factors
• smoking, diet, alcohol
• chemoprevention
• tamoxifen breast
• finasteride prostate -investigational
• retinoids head and neck -investigational

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Etiology of Cancer

• Environmental factors
• Viruses
• Lifestyle factors
• Medical - Drugs and Hormones
• Hereditary

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Environmental Factors

• Industrial/Occupational
• Coal miners, factory workers, asbestos
• Ultraviolet Light
• ? risk of skin cancers
• Ionizing Radiation (Lifestyle Factor?)
• X-rays, nuclear weapons or accidents
• evidence from Japan Chernobyl
• ? risk of breast cancer and leukemias
• Thyroid irradiation (for hyperthyroid)
• ? risk thyroid cancer

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Viruses

• Epstein-Barr virus - Hodgkins lymphoma
• Human Immuno-deficiency virus - NHL and Kaposis
  sarcoma
• Human Papilloma virus - Cervical cancer
• Hepatitis A, B - Hepatocellular cancer
• HTLV-1 - T-cell leukemia

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Lifestyle Factors

• Tobacco - Cigarette Smoking
• lung, oropharygeal, and bladder cancers
• If cigarettes did not exist lung cancer would be
  an rarity
• Radon
• lung cancer
• Electromagnetic fields
• cell phones and high tension power lines
• causal relationship ?

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Lifestyle Factors

• Alcohol
• associated with several cancers including
  esophogeal, liver, oropharynx, breast and larynx
• usually associated with another carcinogen
• Diet
• implicated in colorectal cancer
• Decrease Fat, Increase Fruits and Vegetables

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Drugs and Hormones

• Alkylating Agents
• Cyclophosphamide - bladder
• melphalan - leukemia
• Antimetabolites
• Azathioprine - NHL, skin
• Corticosteroids
• Prednisone - NHL

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Drugs and Hormones

• Estrogens
• Diethylstilbestrol - vaginal Ca in offspring
• Combined Modalities
• Chemo Radiation - leukemia
• Others
• Phenacetin - renal
• Phenytoin - liver (rats)
• Chloramphenicol - leukemia

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Hereditary/Genetic

• Cancer as Primary Manifestation
• Retinoblastoma, neuroblastoma, pheochromocytoma
• Inherited Condition
• Familial polyposis, Fanconis anemia, xeroderma
  pigmentosum
• Inherited Disease of Immune System
• Wiskott-Aldrich Syndrome
• Chromosomal Aberrations
• Downs Syndrome, Fanconis anemia

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Hereditary/Genetic

• Breast cancer
• If first degree relative has(d) breast cancer
  greatly increases the risk
• BRCA1 mutation
• Retinoblastoma
• Rb

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Genetic Regulation

• Oncogenes/Proto-Oncogenes
• normal exons which when mutated promote
  oncogenesis
• wt proto-oncogene (no tumor promoting effect)
• mutant oncogene
• Tumor Suppressor Genes
• Genes which regulate cell proliferation and
  prevent cell from dividing out of control
• wt prevent cell from becoming a tumor
• mutant unable to prevent tumor-genesis

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Proto-Oncogenes and Malignant Transformation

• N-myc transcription factor
• Neuroblastoma
• Erb-B(her2neu) cell surface receptor
• Breast cancer
• RAS intracellular messenger
• Acute Myeloid Leukemia
• BCL transcription factor/apoptosis
• Chronic Myeloid Leukemia

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Tumor Supressor Genes

• Rb (cell cycle)
• retinoblastoma, osteosarcoma
• p53 (growth arrest/apoptosis)
• sarcomas, breast, and brain tumors
• BRCA1 and BRCA2 (DNA repair)
• breast and ovarian tumors
• E-Cadherin (cell adhesion regulator)
• breast, colon, skin, and lung

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Cell Cycle Entry to Death Regulation
Growth Factor
Receptor Activation
Intracellular Kinase Cascade
Early Nuclear Proteins (myc, fos, jun etc.)
Cell Cycle Activators (cyclins)
Regulators (Rb)
Genome Checkers (p53)
Apoptosis Cell Cycle Balancers (bcl-2 family)
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Malignant Transformation

• Genetic alterations transform normal cells into
  malignant cells
• Two (multiple) hit hypothesis
• predisposition external factor
• multiple external factors

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Questions?