PUBH 420 - WEEK 11APRIL 2, 2014

Cancer & Neoplasm Biologyin Public Health

Outline: Cancer & Neoplasm Biology

! Cancer Epidemiology! “The Big Picture” of Cancer! Risk Factors! Nomenclature! “Causes” of Cancer & The Cancer Process

! Agents, classifications! Concepts & Mechanism

! Treatments

Cancer Epidemiology: Explanations

Cancer Epidemiology

Neoplasm (New Growth) aka Tumor

! mass of abnormal tissue (Distinct or non-Distinct)! Grows by cell proliferation (not hypertrophy)! Can be benign

-relatively harmless; -no invasion or distant spread

! or malignant ! Cancer: malignant neoplasm! Cancer: progressive, harmful behavior: intrusion on nearby

tissue, destruction, distant spread (metastasis).

“The Big Picture” of Cancer

! Study of Cancer: Oncology

! Class of diseases– not one disease; very complex! # of diseases, differ in

" origin" prognosis" treatment

! What “causes” one type doesn’t *directly* cause another usually

! Commonality: cells display uncontrolled growth, local invasion, and spreading (metastasis )

Big Picture

! Body is a society of cells

! Function of society, members (cells) have jobs, responsibilities, and rules (or cell division) for how they conduct; cancer cell is “rogue” cell.

! Does not comply with rules; changes in genes and their expression

! Over time, rogue cell (steals nutrients, invades) can bring down the entire organism

Malignant cells Develop over YearsCancer is a Process

Risk Factors

! Etiology for most is unknown.

Factors:! Genetic (predisposition) ! Environment (UV, pollutants)

! Pollution, heavy metals! Behavior/ Lifestyle (lack of exercise, some high-fat diets)! Viruses (e.g. HPV)

! Epigenetic (gene expression alteration (not gene itself) –combination)

Exogenous vs Endogenous Risk Factors

• (1/3)Tobacco (smoking)

• (1/3)Diet, lack of exercises, obesity

• Irritation• UV radiation• Excess Alcohol• Infectious Disease

• HPV• Hep B

• Inherited gene traits: Endogenous Risk

Irritation as a Factor for Cancer

! Increased damage/death of cells! Increase repair attempts/ division

! Stomach cancer, lung cancer

Asbestos & Smoking

05101520253035404550

No)Exposure Asbestos Smoking Asbestos)+Smoking

Risk)Multiplier

(70%per%100,000%lung%cancer%deaths%in%general%population)

Lung Cancer Risks

5x%higher%risk%than%general%population

10x%higher%risk

50x$to$90x$higher$risk

Benign: Nomenclature of Tumors

! Anything *just*- oma = some kind of tumor! E.g. Lipoma, Chondroma, Adenoma! *usually* benign

! Sometimes malignant:" Lymphoma: proper: lymphosarcoma" Melanoma

Malignant: Nomenclature of Tumors

! If Malignant:! -oma " -carcinoma or –sarcoma

! Refers to embryonic germ layer from where tissue originates

! Ectoderm or Endoderm = -carcinoma

! Mesoderm = -sarcoma

Tumor Nomenclature: Embryonic Layer

• Ectoderm: Exterior (e.g. skin)

• Endoderm (digestive tract, respiratory, organs)

• Mesoderm: Bone, muscle, cartilage, reproductive organs, blood vessels

Tumor Nomenclature

" Sarcoma—mesoderm Greek: sarx (flesh)

! What is the suffix?! Basil cell -, squamous cell -? (ectoderm)

! Fat tumor-- lipo? –malignant versus non malignant (Mesoderm)

! Chondroma vs Chondrocarcinoma vsChondrosarcoma?

“Causes” cancer

! “causes” cancer:

! “Exposure to Agent X increases the observed incidence of cancer in a dose-dependent manner”

! Consider “causative agents” risk factors

Mechanism & Concept Introduction

! Malignant cells Develop over Years! Cancer is a Process

! Multi-step process of microevolution

! Must have at least 5 – 10 *key* critical mutations in genes important for " cell division " Apoptosis*" DNA repair

Cancer Concepts: Selective Advantage“Microevolution”

Each small mutation for cell = small selective advantage for cell.

Cancer Concepts

! Complex multi-step process over decades ! Series of gene abnormalities that program uncontrolled,

unregulated growth. ! Change in

! Apoptosis! DNA repair! Cell Division

Question: If apoptosis is changed, how is this an advantage?

Carcinogenesis Process

! 1) Initiation! Cells exposed to agent undergo change in DNA

! 2) Promotion! Cells stimulated to divide

! 3) Progression! Mass of cells become clones that damage host

Repeated cycles of altered DNA (Initiation),Selective pressure of growth (Promotion)

Carcinogensis

! Tumor Suppressor genes " Brake! P53 gene; detects DNA damage " apoptosis! When altered, doesn’t go through

! Oncogenes " Gas Pedal (to floor)! Proto-oncogenes

! Analogy: Red Light (Oncogenes = Runs Red Light, Go anyway)

! Red Light: (TSG : Broken Brakes)

Carcinogenesis

Why Age?

Radiation

Oxidants(free radicals) –injure cell

Treatment Types

! Surgery (if cancer is not spread, greatest chance for cure)

! Chemotherapy (cytotoxic drugs)! Kill cells that divide rapidly (and sometimes normal dividing

cells (aka hair)! New agents (targeted)

! Radiation Therapy – uses high-energy particles to destroy or damage cells.

Treatment Types

! Immunotherapy! Uses own immune system to recognize cancer division

! Hormone Suppressor: Tamoxifen! Stem cell transplant: Bone marrow

! Combination of Chemo & Radiation; then insertion of stem cells

! Photodynamic Therapy (PDT)! Drug photosensitizer + wavelength of light (laser) " oxygen

form that kills nearby cells

Summary

! Cancer is Process: not one disease!

! Factors: Genetic, Environmental, Epigenetic

! -oma (benign), -Carcinoma (Endo, Ecto)

! 5-10 critical mutations in apoptosis, DNA repair

! Oncogenes & Tumor Suppressor Genes

References

! www.cancer.org! http://www.cancer.org/treatment/treatmentsandsid

eeffects/treatmenttypes/! Dr. Tominack, Rebecca: Director of the Missouri

Poison Center! http://kch.illinois.edu/images/Research/Labs/Canc

erEpidemiology/cancer-map_lg.jpg! National Cancer Institute