Cancer

Hadil S. Subih,
Ph.D.
 What is cancer?
0

• Cancer is a term used for diseases in which abnormal

cells divide without control and are able to invade
other tissues.
• Cancer cells can spread to other parts of the body
through the blood and lymph systems.
 What is cancer?
0

• Cancer is not just one disease but many diseases. There

are more than 100 different types of cancer.
• Most cancers are named for the organ or type of cell in
which they start
• For example, cancer that begins in the colon is
called colon cancer; cancer that begins in basal cells
of the skin is called basal cell carcinoma.
 Different kinds of cancer
0
Cancer Prefixes Point to Location

Prefix Meaning

0
adeno- gland

chondro- cartilage

erythro- red blood cell

hemangio- Blood vessels

hepato- liver

lipo- fat

lympho- lymphocyte

melano- pigment cell

myelo- bone marrow

myo- muscle

osteo- bone
 Fast facts about cancer
0

• One in three people will develop cancer.

• One in four people will die of cancer.
• In 2007, more than 1.5 million new cases of cancer
were diagnosed.
• More than 1500 Americans die of cancer each day.
• Over 1,000,000 cases of skin cancer will be
diagnosed this year.
 Major causes of death
0
 CVD deaths vs cancer deaths
0
0

The Biology of Cancer

 Cancer biology
0

• Cancer is a disorder of altered cell differentiation

and growth.
• The resulting process is called neoplasia, and the
tissue, a neoplasm.
 Neoplasm
0

• A neoplasm can be thought of as an attempt by the

body to make some sort of new organ in response
to some type of stimulus.
• Neoplasms have the following characteristics:
• Uncontrolled cell growth and division
• Neoplasms tend to increase in size and continue to
grow after the initial stimulus is removed
 Cell proliferation
0

• Tissue renewal and repair, as well as the

pathogenesis of cancer, involves cell proliferation,
differentiation and apoptosis.
• Cell proliferation is the process whereby tissues
acquire new or replacement cells through cell
division.
 Cell proliferlation
0

• The permanent cells are unable to divide and

reproduce.
• Neurons and cardiac muscle cells (more specialized
cells)
• The stable cells are normally renewed more slowly
but are capable of more rapid renewal after tissue
loss.
• Liver cells
• The labile cells are in a constant state of renewal.
• Epithelial cells lining of the gastrointestinal tract and
the cells of the hematopoietic system
 Cell differentiation
0
 Cell differentiation
0
 Cell cycle
0

• The cell cycle is the interval between each cell

division, regulates the duplication of genetic
information and appropriately aligns the
supplicated chromosomes to be received by the
daughter cells.
 Cell cycle
0

G
0
 Cell cycle
0

• Interphase accounts for about 90% of the cell

cycle.
• The cell grows and copies its chromosomes in
preparation for cell division in interphase.
• G1 Phase (First Gap)
• S Phase (Synthesis)
• G2 Phase (Second Gap)
• G0 Phase (Quiescent)
0

The cell cycle can be divided in three periods:

•Interphase: during which the cell grows,
accumulating nutrients needed for mitosis preparing
it for cell division and duplicating its DNA
•Mitotic (M) phase: during which the cell splits itself

into two distinct cells, often called "daughter cells"

• Final phase
0

• G0: A resting phase where the cell has left the cycle and has
stopped dividing.
• G1: Cells increase in size in Gap 1. The G1 checkpoint control
mechanism ensures that everything is ready for DNA
synthesis.
• S: DNA replication occurs during this phase.
• G2: During the gap between DNA synthesis and mitosis, the
cell will continue to grow. The G2 checkpoint control
mechanism ensures that everything is ready to enter the M
(mitosis) phase and divide.
• M: Cell growth stops at this stage and cellular energy is
focused on the orderly division into two daughter cells. A
checkpoint in the middle of mitosis (Metaphase Checkpoint)
 Cell cycle checkpoints
0
 Cell cycle checkpoints
0

• G1 checkpoint is the “restriction point” in mammal

cells.
• If a cell gets a go-ahead signal at the G1
checkpoint, it will usually complete the cycle and
divide.
• If a cell does not receive the go-ahead signal at the
G1 checkpoint it will exit the cycle, switching into
a non-dividing state called G0 phase.
 Apoptosis
0

• Cell lifespan
• Born
• Proliferation and differentiation
• Function
• Die (through necrosis and apoptosis)
• Apoptosis is a form of programmed cell death
designed to eliminate senescent cells or unwanted
cells.
 Benign and malignant neoplasms
0

• Neoplasms can be either MALIGNANT or

BENIGN
• Malignant: a neoplasm which will invade and destroy
the surrounding tissue, spread to distant sites
(metastasize).
• Cancer and malignant neoplasm are synonymous
• Benign: a neoplasm which will compress but not
invade the surrounding tissue
• Their cells are microscopically similar to their tissue it
origin and are clustered together in a single mass.
benign cancer
can themilgnant
cancer
develop to

No
 Benign neoplasms
0

• Characteristics of benign neoplasms (tumors)

• Well-differentiated cells that resemble cells in the
tissue of origin.
• Grows progressively and slowly; may come to a
standstill or regress.
• Grows by expansion without invading the surrounding
tissues; usually encapsulated.
• NEVER spread by metastasis
• If it metastasizes it has turned malignant
 Malignant neoplasms
0

• Characteristics of malignant neoplasms (tumors)

• Cells are undifferentiated, with atypical structure that
often bears little resemblance to cells in the tissue of
origin.
• Rate of growth is variable and depends on level of
differentiation; the more undifferentiated the cells, the
more rapid the rate of growth.
 Malignant neoplasms
0

• Characteristics of malignant neoplasms (tumors)

• Grows by invasion, sending out processes that
infiltrate the surrounding tissues.
• Gains access to blood and lymph channels to
metastasize to other areas of the body.
 Mutation of a cell line
0
 Metastasis
0

• How tumor cells invade

• Local infiltration
• Invasion of surrounding tissue
• For some reason, cartilage, tendon and elastic tissue almost
never get invaded
 Metastasis
0

Metastatic Spread
• Seeding of serosal surfaces
• Mechanical transplantation
• Via the lymphatics
• Via blood vessels
 Metastasis
0

• Regardless of the route of metastatic spread, certain

tumors have unexplained preferences for certain
metastatic sites
• Common sites include lymph nodes, lung, liver, bone
and brain
Metastasis
0

Angiogenesis is the
physiological process
through which new
blood vessels form
from pre-existing
vessels

Intravasatin: invasion
of cancer cells through
the basal membrane
into a blood or lymph

Extravasatin: cancer
cells entering another
organ.
 of
because
0

Tumer cell
transformation

An oncogene is a gene
that has the potential
to cause cancer
W

product
End
 Etiology
0

• Cancer growth is controlled by three types of

genes:
1. Oncogenes promote cell growth in cancer cells.
2. Tumor suppressor genes inhibit the proliferation
of cells in a tumor.
3. Genes that control apoptosis
 Etiology
0

• Only when oncogenes are activated, tumor

suppressor genes are inactivated, and apoptotic
genes are altered, neoplastic phenotype are
expressed.
 1
Etiology I
0

r
T S
1
2
3
 Etiology
0

• Heredity
• Hormones
• Chemical carcinogens
• Radiation
• Oncogenic viruses
• Sun exposure
• Tobacco
• Physical inactivity
• Obesity
Etiology
0
 Loss of normal growth
several
happen
Sureshould
0 11s
Cancer
development
0
 Cancer staging
0

• Most tumors can be described as stage 0, stage I,

stage II, stage III, or stage IV.
• Physical exams, imaging procedures, laboratory tests,
pathology reports, and surgical reports provide
3
information to determine the stage of the cancer.
 Cancer staging
0

• The common elements considered in most staging

systems are as follows:
• Site of the primary tumor.
• Tumor size and number of tumors.
• Lymph node involvement (spread of cancer into lymph
nodes).
• Cell type and tumor grade (how closely the cancer cells
resemble normal tissue cells).
• The presence or absence of metastasis.
 Cancer staging
0

spread
didn't
 Treatment
0

• Surgery
• Radiation therapy
• Chemotherapy
Accordingtothe
casewedecide
thetreamentmay beonetreatmentor
twoor or c
t hree t hem naivaiuai.es
 Lung cancer
0

These cancers are categorized by small cell or

non-small cell carcinomas.
 Lung cancer risk factors
0

• Smoking — about 87 percent of lung cancers are

related to smoking
• Exposure to substances such as arsenic, asbestos,
radioactive dust or radon
• Radiation exposure from work, medical or
environmental sources
• A family history of cancer
 Lung cancer and smoke
0

e
0
 Lung cancer symptoms
0

• Cough that does go away and gets worse over time

• Chest pain
• Shortness of breath, wheezing, or hoarseness
• Weight loss and loss of appetite
• Coughing up blood
• Fever without a known reason
• Repeated problems with pneumonia and bronchitis
 Lung cancer types and screening
0

• Non small cell lung cancer (80%)

• Small cell lung cancer (20%)
• No recommended screening test for lung cancer.
 Colon cancer
0

• The colon and rectum comprise the large intestine

(large bowel)
• The primary function of the large bowel is to turn
liquid stool into formed fecal matter
 Colon cancer
0

0
 Colon cancer
0

• Polyp Advanced cancer

E
of
 Risk factors for colon cancer
0

• Uncontrolled risk factors

• Personal or family history of cancer
• Age
• Controlled risk factors
• Inflammatory bowel disease (IBD)
• Diet high in saturated fats, red meat
• Diabetes
• Overweight or obesity
• Lack of exercise
• Smoking
• Polyps
 Symptoms of colon cancer
0

• A change in bowel habits such as diarrhea,

constipation, or narrowing of the stool that lasts for
more than a few days
• A feeling that you need to have a bowel movement
that doesn't go away after doing so
• Rectal bleeding, dark stools, or blood in the stool
(often, though, the stool will look normal)
• Cramping or stomach pain
• Weakness and tiredness
 Colon cancer screening
0

• Annual fecal occult blood test

• Double Contrast Barium Enema (DCBE)
 Colon cancer screening
0

Sigmoidoscopy Colonoscopy
 Breast cancer
0

Mammary gland
 Types of breast cancer
0

• Ductal carcinoma in situ (DCIS)

• Lobular carcinoma in situ (LCIS)
• Invasive (infiltrating) ductal carcinoma (IDC)
• Invasive (infiltrating) lobular carcinoma (ILC)
• Inflammatory breast cancer (IBC)
 Risk factors for breast cancer
0

• Uncontrolled risk factors

• Race
• Age
• Personal or family history of cancer
• Genetic risk factors
• Dense breast tissue
• Menstrual periods
• Earlier breast radiation
 Risk factors for breast cancer
0

• Controlled risk factors

• Not having children or having them later in life
• Recent use of birth control pills
• Postmenopausal hormone therapy (PHT)
• Not breast-feeding
• Lack of exercise
• Being overweight or obese
 Symptoms of breast cancer
0

• Swelling of all or part of the breast

• Skin irritation or dimpling
• Breast pain
• Nipple pain or the nipple turning inward
• Redness, scaliness, or thickening of the nipple or
breast skin
• A nipple discharge other than breast milk
• A lump in the underarm area
 Breast cancer screening
0

• Yearly mammograms
are recommended
starting at age 40.
• Clinical breast exam
• Breast self-exam
 Prostate cancer
0

Bladder

Normal prostate
urethra

Prostate cancer
 Risk factors for prostate cancer
0

• Uncontrolled risk factors

• Age
• Family history

• Controlled risk factor

• Eat more red meat, fewer fruits and vegetables
 Symptoms of prostate cancer
0

• Early prostate cancer often causes no symptoms

• Symptoms of advanced prostate cancer
• Trouble having or keeping an erection (impotence)
• Blood in the urine
• Pain in the spine, hips, ribs, or other bones
• Weakness or numbness in the legs or feet
• Loss of bladder or bowel control
 Liver cancer
0
 Risk factors for liver cancer
0

• Uncontrolled risk factors

• Gender (Men > women)
• Inherited Metabolic Diseases
• Controlled risk factors
• Certain Types of Chronic Viral Hepatitis
• Diabetes
• Obesity
• Aflatoxins
• Vinyl Chloride and Thorium Dioxide (Thorotrast)
• Anabolic Steroids
• Arsenic
 Symptoms of liver cancer
0

• Early liver cancer often causes no symptoms

• Signs of liver cancer are relatively non-specific
• Unexplained, unintentional weight loss
• Constant loss of appetite
• Feeling very full after a small meal (early satiety)
• Enlarged liver
• Enlarged spleen
• Persistent pain in the abdomen
• Swelling or fluid build-up in the abdomen
• Skin itching, yellowing of the skin and eyes (jaundice)
 Liver cancer screening
0

• Because signs and symptoms do not usually appear

until the cancer is in its later stages, liver cancer is
seldom diagnosed early.
• Alpha-fetoprotein (AFP) blood test
• Ultrasound
 Cancer prevention
0

• Choose a diet rich in a variety of plant-based foods.

• Eat plenty of vegetables and fruits.
• Maintain a healthy weight and be physically active.

• Select foods low in fat and salt.

• Prepare and store food safely.

i
 Diet
0

• Evidence for the influence of dietary factors and

cancer is uncertain.
• Both fruits and nonstarchy vegetables were
associated with “probable decreased risk” for
cancers of the mouth, esophagus, and stomach.
• Fruits, but not nonstarchy vegetables, were also
judged to be associated with “probable decreased
risk” of lung cancer.
 Maintain a desirable weight
0

• Obesity was first proposed as a potential risk factor

for several cancers over thirty years ago.
• Obesity is being increasingly recognized as an
important cancer risk factor.
 Cancers associated with Obesity
0

Woman Man
•Breast (postmenopausal) • Prostate
•Endometrium • Colorectal
• Cervical • Kidney
•Ovarian •Liver/ Gall Bladder
•Colorectal •Pancreatic

• Kidney •Esophageal
• Liver/ Gall Bladder •Hematopoietic

•Pancreatic risk
Obesity the
increase
and
men
both
•Esophageal
cancerfor
of
women

• Hematopoietic
 Body weight, cont.
0

• Excess calorie intake in animals has a significant

influence on the appearance of spontaneously, or
chemically or radiation-induced cancers
• Tumor yield is much higher in rodents allowed to
consume food ad libitum compared to those given
s
calorie restriction
 Body weight, cont.
0

• Calorie restriction appears to exert a more powerful

effect on cancer than fat restriction
• Calorie restriction appears to reduce metabolic rate.
body temperature, free radical generation, and genetic
mutations.
• Calorie restriction may also increase the body’s ability
to detoxify carcinogens.
 Physical activity
0

• A growing body of epidemiologic evidence

suggests that people who are more physically
active have a lower risk of certain malignancies
than those who are more sedentary.
 Vitamin and dietary supplement use
0

• Some have advocated vitamin and mineral

supplements for cancer prevention.
• Many different mechanistic pathways for anticancer
effects have been invoked.
 Vitamin and dietary supplement use
0

• A commonly tested hypothesis is that antioxidant

vitamins may protect against cancer, based on the
premise that oxidative damage to DNA leads to
cancer progression.
• Hence preventing oxidative DNA damage would
prevent progression to cancer.
• However, the evidence is insufficient to support the
use of multivitamin and mineral supplements or
single vitamins or minerals to prevent cancer.
 Vitamin and dietary supplement use
0

• Beta carotene is an antioxidant that was thought to

prevent or reverse smoking-related changes leading
to lung cancer, based on the results of several
observational epidemiologic studies
• However, few prospective placebo-controlled trials
found that smokers and former smokers who
received beta carotene supplements had increased
lung cancer incidence and mortality.
 Vitamin and dietary supplement use
0

• Research into the potential anticancer properties of

vitamin and mineral supplements is ongoing, and
the results continue to reinforce the lack of efficacy
of vitamin supplements in preventing cancer.
• Results from several large-scale randomized trials
were published in early 2009. The results of the
Selenium and Vitamin E Cancer Prevention Trial
indicated that taking daily selenium or vitamin E or
both did not reduce the incidence of prostate cancer
compared with placebo.
 Vitamin and dietary supplement use
0
• The results of the Women’s Antioxidant
Cardiovascular Study indicated that, compared with
placebo, supplementation with vitamin C, vitamin
E, or beta carotene was not efficacious in reducing
total cancer incidence.
• In this same study, daily supplements containing
folic acid, vitamin B6, and vitamin B12 were
compared with placebo; this intervention was not
efficacious in reducing the overall risk of
developing cancer.
 Vitamin and dietary supplement use
0

• An exploratory analysis of pooled data from two

Norwegian randomized controlled trials showed an
increase in both cancer incidence and cancer death
in patients treated with folic acid and vitamin B12
versus those receiving placebo or vitamin B6 alone.
 Environmental Exposures and
0 Pollutants
• Cigarette smoking and infections have represented
much greater proportions of the cancer burden than
have environmental pollutants.
• Perhaps because the lung is most heavily exposed
to air pollutants, many of the most firmly
established examples of pollutants and cancer relate
specifically to lung cancer, including secondhand
tobacco smoke, indoor radon, outdoor air pollution,
and asbestos for mesothelioma.
 Environmental Exposures and
Pollutants
0

• Another environmental pollutant linked with cancer

is highly concentrated inorganic arsenic in drinking
water, which is causally associated with cancers of
the skin, bladder, and lung.
• Many other environmental pollutants, such as
pesticides, have been assessed for risk with human
cancer, but with indeterminate results.
Grading system for benefit vs. harm: Nutrition during and after cancer treatment A1:
Proven benefit; A2:Probable benefit, but unproven; A3: Possible benefit, but unproven;
B: Insufficient evidence to conclude benefit or risk; C:Evidence of possible harm and
benefit; D:Evidence of lack of benefit; E: Evidence of harm
0

Dietary factors Prostate Breast lung

Food safety A1 A1 A1
Intentional weight loss during E E E
treatment
Intentional weight loss after B A2 B
recovery
Decreased dietary fat A3 A2 B
Increased fruits and vegetables B A3 A2
Increased physical activity A3 A2 B
Fasting therapies D D D
Juice therapies B A3 A3
Grading system for benefit vs. harm: Nutrition during and after cancer treatment A1:
Proven benefit; A2:Probable benefit, but unproven; A3: Possible benefit, but unproven;
B: Insufficient evidence to conclude benefit or risk; C:Evidence of possible harm and
benefit; D:Evidence of lack of benefit; E: Evidence of harm
0

Dietary factors Prostate Breast lung

Macropiotic therapies C C C
Vegetarian therapies A3 A3 A3
Vitamin and mineral supplement A3 B C
Flaxseed oil B B B
Fish oil B B B
Genger B B B
Soy foods C C B
Teas B B B
Grading system for benefit vs. harm: Nutrition during and after cancer treatment A1:
Proven benefit; A2:Probable benefit, but unproven; A3: Possible benefit, but unproven;
B: Insufficient evidence to conclude benefit or risk; C:Evidence of possible harm and
benefit; D:Evidence of lack of benefit; E: Evidence of harm
0

Dietary factors Prostate Breast lung

Vitamin E supplements A3 B B
Vitamin V supplements B B B
ß-carotene supplements C C E
Selenium A3 B A3
 Cancer prevention research — then and
now
0

• To date none have been verified as effective in clinical

trials
Cancer prevention research — then and
now
0
 Guidelines on Nutrition and Physical
Activity for Cancer prevention
0

• Maintain a healthy weight throughout life.

• Adopt a physically active lifestyle.
• Adults: Engage in at least 30 minutes of moderate to
vigorous physical activity, above usual activities, on 5
or more days of the week; 45 to 60 minutes of
intentional physical activity are preferable.
• Children and adolescents: Engage in at least 60
minutes per day of moderate to vigorous physical
activity at least 5 days per week.
 Guidelines on Nutrition and Physical
Activity for Cancer prevention
0

• Eat a healthy diet, with an emphasis on plant

sources.
• Choose foods and drinks in amounts that help achieve
and maintain a healthy weight.
• Eat 5 or more servings of a variety of vegetables and
fruits each day.
• Choose whole grains over processed (refined) grains.
• Limit intake of processed and red meats.
0
Cancer prevention research — then and
now
Complete strategy for
eliminating cancer