Genes and Cancer

Prof. Arnaldo Ferreira

Impacts, Issues: Between You and Eternity

Cancer strikes one in three people in the United States
Kills one in four

Overall more males than females get cancer

Pattern varies depending upon the type of cancer

Gene mutations and cancer

BRCA1 and BRCA2: breast cancer susceptibility genes

The Characteristics of Cancer

As genes switch on and off, they determine when and how fast the cell will grow and divide, when it will stop dividing, and even when it will die Cancer can result when controls over cell division are lost

Some Tumors Are Cancer, Others Are Not

Hyperplasmia Cells in a tissue overgrow Resulting defined mass: tumor (neoplasm)
Benign, e.g., moles
Slow growth Expands in the same tissue; does not spread Cells look nearly normal

Malignant
Rapid growth Invades surrounding tissue and metastasizes Cell differentiation usually poor

Some Tumors Are Cancer, Others Are Not

Dysplasia Abnormal change in the size, shape, and organization of cells in a tissue Often an early step toward cancer
Microscopic characteristics of cancer cells Behave differently from normal cells

Cancer Cells Are Abnormal in Their Growth and Appearance

Normal Moles Are Common Examples of Benign Growths

Main Features of Benign and Malignant Tumors

A Cancer Cells Structure Is Abnormal

Cancer is a result of a series of mutations in the cells genes
Larger cell nucleus and less cytoplasm Loss of structural specialization Cytoskeleton shrinks Plasma membrane proteins could be lost or altered New plasma membrane proteins may appear Changes passed on to cells descendants

Cancer Cells Also Do Not Divide Normally

Cancer cells dont necessarily divide faster than normal cells; more cancer cells are dividing than dying Cancer cells do not respond to crowding; loss of contact inhibition
Leads to a disorganized mass; cells may have extensions May produce HCG and angiogenin Metastasis: makes a cancer malignant

Threadlike False Feet Are a Common Feature of Cancerous Cells

Cancer Spreads Step-by-Step

Cancer is a Genetic Disease

Cancer is a genetic disease that develops in a predictable sequence of steps Carcinogenesis
Transformation of a normal cell into a cancerous cell Step-by-step transformation

Carcinogenesis Occurs in Predictable Steps

A Common Type of Colorectal Cancer May Develop by These Steps

Colon cancer results from genetic alterations in multiple genes

Inherited mutations in the APC gene dramatically increase risk of colon cancer

Cancer Usually Involves Several Genes

Proto-oncogenes
In normal cells
Code for proteins involved in the stimulus of cell division

If altered, may form oncogenes

Alone, do not cause malignant cancer Require other mutations, including one in a tumor suppressor gene

Cancer Usually Involves Several Genes

Tumor suppressor genes
Stop cell growth and division; prevent cancer formation May prevent expression of oncogenes Retinoblastoma: only one functional copy of a tumor suppressor gene on chromosome 13 BRCA1 and BRCA2 p53: codes for a regulatory protein that turns off cell division when the cell is stressed or damaged
If mutated, runaway cell division More than half of cancers has a mutated or missing p53 gene

Types of cancer genes

Type of gene Normal function Mutated function Types of proteins
Oncogene Promotes division Promotes division Growth factors - abnormal time or cell type Suppresses cell division Fails to suppress division Checkpoint molecules

Tumor suppressor gene

DNA repair Repair DNA gene mutation mutations

Fail to repair DNA mutations

Enzymes for mismatch or excision repair

Other Factors Also May Lead to Cancer

Inherited susceptibility to cancer
~5% of cancers

Viruses
Viral DNA may be inserted into a host cells DNA
May switch on a proto-oncogene May carry oncogenes

Other Factors Also May Lead to Cancer

Chemical carcinogens
Carcinogens: cancer-causing substances that can lead to a mutation in DNA
Asbestos, vinyl chloride, and benzene Hydrocarbons in cigarette smoke Aflatoxin: fungal product

Radiation
UV from the sun and tanning lamps X-rays: medical and dental Radon, cosmic rays, and gamma radiation

Cruciferous vegetables can lower cancer risk

Other Factors Also May Lead to Cancer

Breakdowns in immunity
Healthy immune system can target and destroy cancer cells When cancer cells have altered proteins at its surface, cells are not destroyed Risk of cancer increases:
With age When an immune system has been suppressed for a long time
HIV infection Immunosuppressant drugs Anxiety and depression

Focus on Environment: Cancer Risk from Environmental Chemicals

Exposure to pesticides
Agricultural chemicals in food and airborne chemicals due to spraying programs Reduce exposure; how?

Industrial chemicals Ames test

Assess chemicals ability to cause mutations

Some Industrial Chemicals Linked to Cancer

Some Major Types of Cancer

In general, a cancer is named according to the type of tissue in which it first forms Sarcomas: cancer of connective tissue Carcinomas: cancer arising from epithelium Lymphomas: cancer of lymphoid tissue Leukemias: cancer of stem cells Gliomas: cancer of brain glial cells

Cancer Is Named for the Site in the Body Where It First Develops

In the U.S., More than 1 Million People Are Diagnosed with Cancer Each Year

Cancer Screening and Diagnosis

Early and accurate diagnosis of cancer is important to maximize the chances that a cancer can be cured

Blood Tests Can Detect Chemical Indications of Cancer

Tumor markers
Produced by particular types of cancer cells Produced by certain cells in response to cancer Detected by blood tests
HCG PSA: prostate-specific antigen

Medical Imaging Can Reveal the Site and Size of Tumors

Medical imaging
MRI (magnetic resonance imaging): reveals tumors obscured by bone X-rays Ultrasound CT (computerized tomography)

Medical Imaging Can Reveal the Site and Size of Tumors

Radioactive tracers
Tracked using a PET scanner
Diagnosis of thyroid cancer using radioactive iodine

Radioactively labeled monoclonal antibodies

Useful in the location and size of certain tumors in the colon, brain, and bone

DNA probe: locates mutated genes, e.g., p53

Radioactive Tracers Also Can Reveal Cancer Tumors

Biopsy Is the Only Sure Way to Diagnose Cancer

Biopsy
Removal and microscopic examination of tissue

Seven common cancer signs: CAUTION

Light Microscope Image Shows Cancerous Cells in Breast Tissue

Cancer Treatment and Prevention

When a person is diagnosed with cancer, a variety of weapons are available to combat it Chemotherapy drugs

Radiation therapy
Surgery

Chemotherapy and Radiation Kill Cancer Cells

Chemotherapy
Drugs used to kill cancer cells; disrupt some aspect of cell division Toxic to healthy cells; hair, bone marrow, lymphocytes, and epithelial cells of intestinal lining Side effects include hair loss, nausea, vomiting, and reduced immune responses Genetic approach to chemo in the future

Chemotherapy and Radiation Kill Cancer Cells

Radiation therapy
Used when cancer is small or has not spread Radioisotopes used, e.g., Ra-226 and Co-60

Chemotherapy and radiation destroy healthy cells

More precise treatments

Monoclonal antibody treatment Interferon treatment; limited at present

Good Lifestyle Choices Can Limit Cancer Risk

Avoid tobacco completely Maintain a desirable weight; eat a low-fat diet with plenty of fruits and vegetables

Drink alcohol in moderation

Make sure your living and work environment is safe from carcinogens Protect your skin from the suns UV rays

This Cancer Cell Is Surrounded by White Blood Cells

Cancer Causes and Contributing Factors

Types of Cancer Skin Cancer

Colon Cancer
Prostate Cancer

Lung Cancer
Liver Cancer

Brest Cancer
Bladder Cancer