cancer the facts

Cancer is not just one disease
More than 200 different types of cancer have been identified
What is cancer?
CANCER

Defining cancer
Cancer is an accumulation of abnormal cells that multiply through uncontrolled
cell division and spread to other parts of the body by invasion and/or distant
metastasis via the blood and lymphatic system
MetastasisTumour growthNormal cells Abnormal cells
Invasion into
surrounding tissues
Uncontrolled
cell division
Spread via blood or
lymphatic system

Incidence of cancer across the globe (2008, estimate)1
Estimated number of new cancer cases
(% of total)
Africa(6%)
Asia(48%)
Europe (25%)
LatinAmericaand Caribbean
(7%)
Northern (13%)
Oceania(1%)
1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v2.0, Cancer
Incidence and Mortality Worldwide: IARC Cancer Base No.10 [Internet]. Lyon, France: International Agency
for Research on Cancer; 2010. Available from: http://globocan.iarc.fr, accessed on 06/06/2013.

Changing prevalence of cancer
Global cancer incidence and
mortality rates continue to rise1
21.3 M
12.7 M
13.1 M
7.6 M
CASES DEATHS
2030
2008
20302002
25 M
people living
with
cancer*2
75 M
predicted to
be living with
cancer2
*Diagnosed in last 5 years
GROWING AND
AGEING POPULATION
ADOPTION OF
UNHEALTHY
LIFESTYLES
IMPROVEMENT IN
DIAGNOSIS/SCREENING
Incidence and Mortality Worldwide: IARC Cancer Base No.10 [Internet]. Lyon, France: International
Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr, accessed on 14/01/2013.
2. The International Agency for Research on Cancer. World Cancer Report 2008. Available from:
http://www.iarc.fr/en/publications/pdfs-online/wcr/, accessed on 06/06/2013.

Common cancers in men and women worldwide1
Incidence and Mortality Worldwide: IARC Cancer Base No.10 [Internet]. Lyon, France: International
Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr, accessed on 06/06/2013.
16.5
13.6
10
9.77.9
4.9
4.4
3
3
27
Men (%) Lung(16.5)
Prostate(13.6)
Colorectum(10.0)
Stomach(9.7)
Liver(7.9)
Oesophagus(4.9)
Bladder(4.4)
Non-Hodgkinlymphoma(3.0)
Leukaemia(3.0)
Otherandunspecified(27.0)
8.5
22.9
9.4
5.83.78.84.8
3.72.7
29.7
Women (%) Lung(8.5)
Breast(22.9)
Colorectum(9.4)
Stomach(5.8)
Liver(3.7)
Cervixuteri(8.8)
Corpusuteri(4.8)
Ovary(3.7)
Thyroid(2.7)
Otherandunspecified(29.7)

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and
Mortality Worldwide: IARC Cancer Base No.10 [Internet]. Lyon, France: International Agency for Research on
Cancer; 2010. Available from: http://globocan.iarc.fr, accessed on 06/06/2013.
2. American Cancer Society. Global Cancer Facts and Figures 2nd Edition. Atlanta: American Cancer Society; 2011.
Global cancer mortality
Both sexes Men Women
0
5
10
15
20
25
Lung
Stomach
Liver
Colorectal
Female
breast
Mortality(%ofallcancertypes)
Approximately 7.56
million people died from
cancer in 2008,1
accounting for 13% of all
deaths (from any cause)2
Lung, stomach, liver,
colorectal and female
breast cancers
cause 50% of all
cancer deaths1

Common terms
Localised
the cancer is still confined
to the site of origin and has
not yet invaded the
surrounding tissues or
spread to other sites
Invasive
the cancer has spread
from the site of origin into
the surrounding tissues
Metastatic
the cancer has spread to
distant sites in the body to
form new tumours
Stage
classification of the cancer,
important for treatment
decisions, based on the
size, presence or absence
of metastasis and involve-
ment of lymph nodes
Grade
how abnormal cancer cells appear in comparison
to normal cells and how aggressive the cancer is
Low grade – nearly normal in appearance;
slow rate of growth and metastasis
High grade – very abnormal-looking cells;
high rate of growth and metastasis

Cancer categories
Carcinoma
cancer of the skin or
tissues that line or
cover the internal
organs
Sarcoma
cancer of bone,
cartilage, muscle, fat,
blood vessels, and
connective tissues
Leukaemia
cancer of the bone
marrow affecting the
white blood cells
Lymphoma
cancer arising in the
lymph glands
Central nervous
system cancers
cancer of the brain or
spinal cord

Making sense of cancer names
Artwork originally created for the National Cancer Institute.
Reprinted with permission of the artist, Jeanne Kelly. Copyright 2013.

Risk factor definitions
RISK FACTOR
Something that increases
the chances of getting
a disease
Intrinsic
risk factor
…is an integral part of
the individual and
cannot be changed
(genetics, age, etc.)
Extrinsic
risk factor
…is related to an
individual’s own actions
and environment
(tobacco, pollution,
diet, etc.)

Risk factors are multiple
and differ according to the cancer type
RISK
FACTORS
Age
Obesity
Bacteria
H.pylori
Hormones
Radiation
Diet
Smoking
tobacco
General
health
Hereditary
Chemicals
Viruses
HPV
HBV
EBV
Sun
exposure

Absolute risk vs. Relative risk
Absolute risk
The risk of an
individual
developing
cancer during
their entire
lifetime
Relative risk
The risk of a
group of people
developing
cancer in
comparison to
another group

Benefits of assessing risk
Allows the individual at risk to undertake prevention
strategies (e.g. stop smoking, avoid radiation)!
Alerts physicians to those individuals at risk of
developing cancer!
Early detection enables physicians to initiate
treatment, whist the tumour is still in the initial stages!
Enables screening procedures to detect cancer at
an early stage!

1. Nowell, PC. The clonal evolution of tumor cell populations. Science (1976) 194:23-28.
2. Cavenee, WK & White, RL. The genetic basis of cancer. Scientific American (1995) 272:72-79.
Emergence of a cancer cell
Malignant cell
Cancers originate
from a single cell1,2
A series of mutations accumulate in successive
generations of the cell in a process known as
clonal evolution
Eventually, a cell
accumulates enough
mutations to become
cancerous
First
mutation
Second
mutation
Third
mutation
Fourth or
later mutation
Genetic mutations, i.e. changes to the
normal base sequence of DNA, contribute to
the emergence of a cancer cell

In order for cancerous cells to develop and form a tumour, mutations
and other alterations that allow the cell to acquire a succession of the
following biological capabilities must occur:1,2
The hallmarks of cancer
1. Hanahan D & Weinberg RA. The hallmarks of cancer. Cell (2000) 100:57-70.
2. Hanahan D & Weinberg RA. Hallmarks of cancer: the next generation. Cell (2011) 144:646-674
Sustaining proliferative signalling
Evading growth
suppressors
Activating invasion
& metastasis
Enabling replicative immortality
Inducing
angiogenesis
Resisting cell
death

Normal cells rely on positive growth signals from other cells
Cancer cells can reduce their dependence on growth signals by:1,2
- Production of their own extracellular growth factors -
- Overexpression of growth factor receptors -
- Alterations to intracellular components of signalling pathways -
Sustaining proliferative signalling
Cell wallIntracellular signalling
Growth factor receptors
Growth factors

• Normal cells rely on
antigrowth signals to regulate
cell growth1,2
• Cancer cells can become
insensitive to these signals
• One way that this can
happen is by disruption of the
retinoblastoma protein (pRb)
pathway1
• pRb prevents inappropriate
transition from the G1 phase
of the cell cycle to the
synthesis (S) phase1
• In cancer cells, pRB may be
damaged, allowing the cell to
divide uncontrollably1
Cell
division
cycle
G1
S
G2
M
Evading growth suppressors

Resisting cell death
Hanahan D & Weinberg RA. The hallmarks of cancer. Cell (2000) 100:57-70. 2. National Cancer Institute, What is Cancer, 2010.
3. Hanahan D & Weinberg RA. Hallmarks of cancer: the next generation. Cell (2011) 144:646-674. Artwork originally created for
the National Cancer Institute. Reprinted with permission of the artist, Jeanne Kelly. Copyright 2013.
An important hallmark of many
cancers is resistance to apoptosis,
which contributes to the ability of the
cells to divide uncontrollably1,2
When normal cells become
old/damaged, they go through
apoptosis (programmed cell death)
Normal cell
division
Cell damage –
no repair
Apoptosis
Cancer cell
division
First
mutation
Second
mutation
Third
mutation
Fourth or
later mutation
Uncontrolled
growth

Another important hallmark of
cancer is the ability of the cell to
overcome the boundaries on how
many times a cell can divide1
These limits are usually set by
telomeres (the ends of
chromosomes):1,2
• In normal cells, telomeres get
shorter with each cell division
until they become so short that
the cell can no longer divide
• In cancer cells, telomeres are
maintained, allowing the cell to
divide an unlimited number of
times
Enabling replicative immortality
Normal cells Cell division Cancer cells
Telomeres
No
apoptosis
Apoptosis
Chromosomes

1.Folkman J. Clinical applications of research on angiogenesis. N Engl J Med (1995) 333:1757-63.
2. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer (2008) 8:579-591.
Inducing angiogenesis
The formation and maintenance
of new blood vessels
(angiogenesis) plays a critical
role in tumour growth.1,2
New blood vessels supply the
cancer cells with oxygen and
nutrients, allowing the tumour to
grow.
Angiogenesis is mediated
principally through vascular
endothelial growth factor (VEGF)
Other growth factors also play a role,
e.g.:
• Fibroblast growth factor (FGF)
• Platelet-derived growth factor (PDGF)
Nearby blood vessels grow into the tumour.
Oxygen and
nutrients Blood vessel
Blood vessel
Pericyte
Endothelial
Smooth
muscle
Cell wall
VEGFRFGFR PDGFR

Activating invasion & metastasis
2. Gupta GP & Massagué J. Cancer metastasis: Building a framework. Cell (2006) 127: 679-695
Eventually, tumours may
spawn pioneer cells that can
invade adjacent tissues and
travel to other sites in the
body to form new tumours
(metastasis)1
This capability allows
cancerous cells to colonise
new areas where oxygen
and nutrients are not
limiting1
Metastasis causes 90% of
deaths from solid tumours2
Nearby blood vessels grow into the tumour.
Oxygen and
nutrients
Cells escape
and metastasiseBlood vessel

There is evidence that a further two emerging hallmarks are involved
in the pathogenesis of cancer1
The acquisition of these hallmarks of cancer is made possible by two
enabling characteristics1
Enabling characteristics and emerging hallmarks
Evading immune
destruction
Enabling characteristics
Genome instability
and mutation
Deregulating cellular
energetics
Tumour-promoting
inflammation
Emerging hallmarks
The immune system is responsible for
recognising and eliminating cancer
cells, and therefore preventing tumour
formation. Evasion of this immune
surveillance by weakly immunogenic
cancer cells is an important emerging
hallmark of cancer.
Cancer cells achieve genome instability
by increasing their mutability, or rates
of mutation, through increased
sensitivity to mutagenic agents or
breakdown of genomic maintenance
machinery.
The uncontrolled growth and division of
cancer cells relies not only on the
deregulation of cell proliferation, but
also on the reprogramming of cellular
metabolism, including increased
aerobic glycolysis (known as the
Warburg effect)
Immune cells infiltrate tumours and
produce inflammatory responses, which
can paradoxically enhance
tumourigenesis, helping tumours
acquire the hallmarks of cancer
Click on each hallmark or enabling characteristic for more information

Diagnostic tests include:
• Physical examination
• Laboratory tests
• Imaging
• Endoscopic examination
• Biopsy
• Surgery
• Molecular testing
How is cancer diagnosed?
‘Cancer’ is an umbrella
term for a broad group of
diseases
There is no single test
that can diagnose all
cancers1
1. Stanford Cancer Institute, Cancer Diagnosis, 2012
If there are symptoms
suggestive of cancer a
broad range of tests
allow HCPs to make an
accurate and detailed
diagnosis

Laboratory tests
Assess the general health of the body
and levels of certain compounds
Typically, blood and/or urine samples
Blood is assessed for its composition,
and can give an indication of liver and
renal function
Blood, proteins and other compounds in
the urine indicate there could be a
problem
Tumour markers detected in blood or
urine are substances created by the
body in response to cancer cells
• Currently, markers are used to
monitor treatment efficacy and
recurrence
• May become more important in
diagnosis in the future
1. Stanford Cancer Institute, Cancer Diagnosis, 2012.
CEA, carcinoembryonic antigen, several cancers can raise
CEA levels; AFP, alpha-fetoprotein; HCG, human chorionic
gonadotropin; CA 15-3 and CA 27-29 are most useful in assessing
advanced breast cancer treatment
Marker Cancer
CA 125 Ovarian
CEA Colorectal
AFP Liver, ovarian, testicular
HCG
Testicular, ovarian, liver,
stomach, pancreatic, lung
CA 19-9 Colon, stomach, bile duct
CA 15-3 Ovarian, lung, prostate
CA 27-29
Colon, stomach, kidney,
lung, ovarian, pancreatic,
uterus, and liver

Imaging
Produce images of the organs
and structures
Reveal location and extent of
disease
Three main types:
• Transmission imaging: high-
energy photons beamed through
body – the ‘opacity’ of different
structures/tissues varies > X-ray,
CT scan, bone scan, mammogram,
lymphangiogram
• Reflection imaging: high
frequency sound reflected
differentially depending on
structures/tissues > Ultrasound
• Emission imaging: atoms excited
to emit energy waves detected by
a scanner > MRI, PET
magnetic field
direction
Imaging
Transmitted
radio waves
Emitted
radio waves

Endoscopy
1. Stanford Cancer Institute, Cancer Diagnosis 2012.
• Bronchoscopy
Used to examine the airways and
obtain tissue samples from the lungs
• Colonoscopy and sigmoidoscopy
Used to view the large intestine or just
the sigmoid colon
• Endoscopic retrograde
cholangiopancreatography (ERCP)
Combined with X-ray to examine the
liver, gallbladder, bile ducts, and
pancreas
• Oesophagogastroduodenoscopy
(upper endoscopy)
Used to view the inside of the
oesophagus, stomach, and duodenum
• Cystoscopy (cystourethroscopy)
Device inserted through the urethra to
examine the bladder and urinary tract
Oesophagus
Endoscope
Stomach
Light
Interior of
stomach
Endoscope
Light
Stomach
lining
Biopsy sample
An endoscope is a small, flexible tube with a light, lens and tools

Biopsy
Biopsy type Description
Endoscopic
Tissue sample removed
via an endoscopy
Bone
marrow
Bone chip or cells
aspirated from the sternum
or hip
Excisional
or incisional
Full thickness of skin even
whole tumour removed
Fine needle
aspiration
(FNA)
Tiny pieces of tumour
extracted via a thin needle
Punch
Short cylinder of tissue
taken
Shave Top layer of skin removed
Skin Small sample of skin taken
Tissue or cells from
the body for
examination under a
microscope
Performed in the
doctor’s office or
hospital, depending
on the type of biopsy
and location of the
tumour

Pathology
1. National Cancer Institute, Understanding Cancer, 2009.
Tests on biopsies and
samples of patient
tissue or body fluids
reveal a great deal
about the cancer
Microscopic
examination can reveal
the presence of cancer
cells, the origin of the
cancer cells (sub-type),
and information on
stage, etc.
Biopsy
Blood sample
or
tissue sample
Pathology
Proteomic profile
Genomic profile

What is TNM?
TNM is a system for classifying malignant tumours!
It is a cancer staging system, which describes
the extent of a person's cancer!
Most medical facilities use this system as their
main method for cancer reporting1!
Most types of cancer have TNM designations,
but some do not1!
1. National Cancer Institute, Cancer Staging, 2010

How does the TNM system work?
The 3 parameters
of the TNM system1:
T = extent of the tumour
N = the extent of spread
to the lymph nodes
M = presence of distant
metastases
A number is
added to each letter
to indicate1:
the size or extent of
the primary tumour
the extent of cancer
spread

T = extent of primary tumour
organ
local tissues
T0 T1 T2 T3
T is classified as follows:1
Tx: Primary tumour cannot be evaluated | T0: No evidence of primary tumour
Tis: Carcinoma in situ (CIS)2 | T1, T2, T3, T4: Size and/or extent of the primary tumour
2. CIS – abnormal cells are present but have not spread to neighbouring tissue; although not cancer, CIS
may become cancer and is sometimes called pre-invasive cancer

N = extent of spread to lymph nodes
distant
nodes
local nodes
N0
N is classified as follows1:
Nx: Regional lymph nodes cannot be evaluated | N0: No local lymph node involvement
N1: Tumour has spread to local lymph nodes | N2, N3: Involvement of local and distant
lymph nodes (number of lymph nodes and/or extent of spread)
N1 N2

M0
M = presence of distant metastases
M is classified as follows1:
Mx: Distant metastasis cannot be evaluated | M0: No distant metastasis
M1: Distant metastasis is present
bone
lung
liver
M1 Mx
?

Intrinsic vs. extrinsic factors
Cancer caused by intrinsic
factors, i.e. inherited mutations,
can only be prevented by
screening and appropriate early
intervention
Cancer Prevention
1. National Cancer Institute, Understanding Cancer, 2009.
Cancer caused by extrinsic
factors can be prevented by
reducing or eliminating exposure
to these factors (e.g. chemicals,
tobacco, radiation, viruses)
Radiation
Viruses
or bacteria
Carcinogenic
chemicals

Tobacco products
1. National Cancer Institute, Understanding Cancer, 2009. 2. WHO Fact Sheet 339, 2012.
The use of tobacco products
is implicated in ~33% of all cancer
deaths1
~1 person dies every 6 seconds
due to tobacco2
The combination of tobacco
and alcohol products appears to
be particularly dangerous1
As well as lung cancer,
tobacco products have also been
implicated in cancer of the mouth,
larynx, oesophagus, stomach,
pancreas, kidney, and bladder1
Avoiding tobacco is the single
most important factor in reducing
cancer risk
Lung Cancer Risk Increases with
Cigarette Consumption1
15x
10x
5x
0 15 30
Lung
Cancer
Risk
Cigarettes Smoked per Day
Non-smoker

Excessive exposure to UV radiation
1. WHO Fact Sheet 305, 2009.
Excessive UV exposure,
particularly in fair-
skinned individuals can
cause:1
• cutaneous malignant
melanoma
• squamous cell carcinoma
• basal cell carcinoma
In 2000, >200,000 cases
of melanoma were
diagnosed worldwide1
Stratosphere
Sun
exposure
Ozone
Epidermis
Dermis
Hypodermis
UV-A
UV-B
UV-C

Diet
National Cancer Institute, Understanding Cancer, 2009.
Unlike tobacco products, UV
radiation and alcohol, dietary
components that influence
cancer risk have been difficult
to determine1
Limiting fat and calorie
intake appears to reduce
cancer risk1
A diet rich in meat
increases cancer risk,
especially colon cancer1
NumberofCases(per100,00People)
Correlation Between Meat
Consumption and Colon Cancer
Rates in Different Countries1
40
30
15
Grams (per person per day)
N.Z.
20
10
0 80 100 200 300
U.S.A.
DEN. CAN
G.B.
SWE
NOR NETH
GERMANY
ICE
ISR
JAM
FIN P.R.
HUNG
ROM
COLNIG
JAPAN
YUG POL
CHILE

HPV Infection Increases Risk for
Cervical Cancer2
Viruses
1. Liao JB. Viruses and Human Cancer. YJBM 2006 (79);115-122. 2.National Cancer Institute, Understanding Cancer, 2009.
Artwork originally created for the National Cancer Institute. Reprinted with permission of the artist, Jeanne Kelly. Copyright 2013.
Worldwide, 15% of all cancers
may be caused by viruses,
including:1
• Epstein-Barr virus
• Human papilloma virus (HPV)
• Hepatitis B virus
• Human herpes virus-8
• Human T lymphotrophic virus
type 1
• Hepatitis C virus
Reducing exposure to these
viruses reduces cancer risk
In the case of HPV, avoiding
unprotected sex with many
partners reduces the risk of
contracting this virus2
High
Low
Non-infected
women
Cervical
Cancer
Risk
Women infected
with HPV

Strategies for prevention
about cancer and risk factors (warnings on cigarette packets,
campaigns about sun and exposure to UV radiation)
pink ribbons for breast cancer,
world cancer day
don’t smoke, stay out of the sun, avoid toxic chemicals and
polluted areas
cervical smear, mammography, colonoscopy
HPV vaccine to reduce risk of cervical cancer; Hep B
vaccine to reduce risk of liver cancer
normal weight, healthy diet, exercise
regular check-ups, seek medical attention early
Education
Awareness
campaigns
Risk
avoidance
Screening
Vaccines
Lifestyle
Healthcare

Breast Cancer Screening
What is screening?
Screening is the name
given to a range of tests
that can detect cancer at
an early stage before
symptoms appear
Finding cancer early
usually means it is easier
to treat/cure
By the time symptoms
appear, the cancer may
have grown and spread
and therefore be more
difficult to treat/cure
1. National Cancer Institute, Cancer Screening Overview, 2012.

Screening: the rationale
For screening to be effective, two requirements
must be met:
A test or procedure must be available to detect
cancers earlier than if the cancer were detected
as a result of the development of symptoms
!
Evidence must be available that treatment initiated
earlier as a consequence of screening results in an
improved outcome
!
1. National Cancer Institute, Cancer Screening HCP, 2012.

Cervical Cancer Screening
Screening tests
National Cancer Institute, Cancer Screening Overview, 2012. Artwork originally created for the National Cancer Institute.
A variety of tests are used in
cancer screening:
• Physical exam and history:
check general health and
review medical history
• Laboratory tests: investigate
samples of tissue, blood,
urine, etc.
• Imaging: visualise the insides
of the body using e.g. x-ray,
ultrasound, CT, MRI, etc
• Molecular tests: look for
specific mutations that are
linked to some types of
cancer
Biopsy
Normal
Pap smear
Abnormal
Pap smear
Patient‘s blood sample
or
tissue sample
Pathology
Proteomic profile
Genomic profile

Screening: pros and cons
Pros
• Reduction in cancer deaths
• 3–35% of premature deaths
due to cancer could be
avoided with screening
• Improved outcomes (does
not apply in all cases)
Cons
• Some screening
procedures carry their own
risks
• False negative results –
patient wrongly assured
there is no problem
• False positive results –
patient may receive
treatment they do not need
1. National Cancer Institute, Cancer Screening HCP, 2012.

Heredity and cancer
Screening and high risk populations
By focusing on high-risk
populations, screening
resources can be better
applied
Patients with a personal
history/strong family
history of cancer are
deemed to be high-risk
The ability to test for
specific genetic mutations
has further refined the
identification of high-risk
patients
National Cancer Institute, Cancer Screening HCP, 2012. Artwork originally created for the National Cancer Institute.
All Breast Cancer Patients
Inherited factor(s) Other factor(s)
Genes and Cancer
Radiation
Viruses
Chem
icals
Heredity
Chromosomes
are DNA molecules

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