Bio Factsneu

BiologicalBasisof Cancer
of cancer.
This Factsheetdescribesthe causes,characteristics, diagnosisand treatment
There are over 200 different forms of cancer,All have a similar origin: the Exam Hint: Learn the detailsof celt division because this will help you
uncontrolled replication of cells, resulting in the formation of fumours' to answer longer essaYquesfions.

Cancers account for about 25oh of all deaths in the UK, and are the
secondbiggest killer aftet cardiovasculardisease.In males, lung cancer
is the most comlnon, whereasin femalesit is breastcancer.
Remember - epidemiologt is the study of the patterns of disease and
the variousfactors that affect the spreadof diseasewithin populations
Tumour DeveloPment
The tumours aise from prob)ems wttlt tbe mechan)sms responsible for
the control of cell division' The problems may be due to:
. mutations:
. abnormal activation of the genesinvolved (if this occurs the genesare
referred to as oncogenes).The genesmay be activatedby carcinogens"
A carcinogen is any agentthat can causethe developmentof cancer.

Fig 1. Cervical smears,showing normal cellsand malignant cells' If these abnormal cells are not recognised by the immune system and
(a) Normal cervical cells suppressed,they will multiply uncontrollably, resulting in the formation
Normal cells have clear cYtoPlasm r)
fi^
^v\r\ ola bundle of identical cells, called the primary tumour' Tumour cells
and nuclei

,is\dp
v\Yc
can break away and spread to other parts of the body by two methods:
. the tumoul cells become mobile by amoeboid action (then called
'tadpole cells') and can migrate into nearby areas'
. the tumour cells can be ffansported in the bloodsffeam and the
lymphatic sYstem.

b? The process of invasion of other body tissues by cells from the prirnary
tumour is called metastasis. This gives rise to secondary tumours or
metastasesin organs such as the liver, adrenal glands and the brain' If the
tumour cells are transportedin the blood the secondarytumour is likely to
be distant from the primary tumour, however if the transport system is the
lymph, it is most likely to occur in a lymph node closeto the original tumour'

Some tumours that form do not spread and are referred to as benign, and
are usually harmless.Tumours that spread,thus causingthe development
of secondarytumours, (which can also spread),are classedas malignant
and can result in seriousillness or death.

Exam Hint: A common (and simpte)mistakels fo confusebenign and

malignanttumours.

Fig 2. Diagram of development and spread of secondarytumours.

Normarcerswhose,:;;;3;1.' bv
removed
not
_ r*"\cm ffffi:xlce's
&p
areactivatedbycarctnosens oC/T v
W,
\ *_

he
Tumour supplied bY blood/lYmPh'
Tumour cells becomemobile,
Tumour gets larger, cells
some enter vesselsand are
ffansported to other organs
vfl, may become mobile
(tadpole cells)

Via blood
Secondary tumour tbrms tn
Tumour (tadpole) cells squeeze lymph node
through wall of caPillary and
invade surrounding tissue

'Tadpole cell lymph node

 Bio Factsbeet
Biologicalbasisof cancer It,w tt,.c u r ri c ul u m Dre ss'c o. u k

Table I Carcinogenic agents.

Relevant information Associatedcancers

in the Skin cancer

Ultraviolet light
(non-ionising radiation).
Wavelengthsbetween250 to 270 nrn
are the most dangerous and are
found in bright sunshine,particularly
since ozone has become dePletedin
the upper atmosPhere.
X-raysr cr, F, T - rays, cosmic raYs. Alpha-raysareheliumnuclei,beta-raysareelectronsorpositrons,
(ionising radiations)
Mutagenic chemicals
Polycyclic hydrocarbons
nitrosamines,aromatic amines'
uv-light energy is absorbed by the niffogenous bases in DNA and results
thymine dimers. These couple across the DNA instead of thymine (Xeroderma
formation of
Most people have pigmentosum).
coupling to adenine,causingthe DNA to develop abnormalbulges.
which
un .nry-. that in light repairs the DNA. Some people have a gene mutation
to be damaged, and this allows the development of skin
causesthe repair .niy-.
UV-light cannot penetratefurther than the epidermis.
cancers.
gamma-raysareelectomagnetic Lung, breast,bone
and act by:
gamma-rays maIToWCancers.
radiation.They all come from radioactivesources.X-rays
. directly breaking DNA and RNA into short lengths'
. splitting water into reactive ionised fragmentswhich damageDNA indirectly.
base Environmentally
Mustard gas adds a methyl or similar alkyl group to guaninealtering its ability to
cancers,such
pair. This causesthe releaseof guanine from DNA so that the position occupied by caused
other chemicals are base analogues as lung cancer
guani.e can then be filled by anotherbase.Many
to the normal basesand so can become incorporated into (linked to polycyclic
which have similar structures
Other hydrocarbons).
the DNA in place of them during replication. An example is 5-bromouracil.
mutagenic chemicals include dioxin, colchicine, caffeine, some pesticides and several
tobaccoproducts. Polycyclic hydrocarbonsare found in soot and tobacco smoke'

Some viruses can contain genesthat when inserted into the host cells DNA become Cervical cancer
Viruses
an (linked to papilloma
EPstein-oncogenes.For example,when a retrovirus such as HIV-I, (an RNA virus), invades
HIV-1,papillomaviruses,
cell it rr., ..u...e to
transcriptase convert the viral RNA into copy DNA' The viruses).
Barrvirus. animal
genes
cDNA can then be insertedinto the host's genomealtering the host's cell division
cell to become malignant. DNA viruses such as the
and switching them on, causingthe
virus contain their own oncogenes, which when inserted into the host's
Epstein-Barr
DNA causeuncontrolled cell division'

Causes of cancer Lung Cancer

The incidenceof some cancersincreaseswith age, for example,cancerof
the gut, skin and urinary tract. Some cancelshave been shown to have a
strong genetic predisposition, such as breast cancer and ovarian cancer'
The genes involved may be oncogenes,or genes that stop the immune
systemfrom recognisingand attacking cancercells thereforeallowing the
developmentof tumours.Also, carcinogens(seeTable 1) can increasethe
chanceof tumour formation.
It is likely that the formation of a malignant cancer cell is caused by
severalfactors operatingover a number of years,rather than being caused
by a single factor alone.
The link between lung cancer and smoking was first identified by
epidemiological studies. By studying and comparing graphs (Fig. 2)
sirowing the number of cigarettessmokedand the number of deathsfrom
lung cancer it was possibleto seethe first evidenceof an association'
Practice exam technique: study the graphsand practisesummansng
the trends shown.tf a questioniusfasks you to describe the data, then
referto the trendsshown and include values,but do not try to explain
the data, because markswitt not be availablefor an explanation.lf you
are askedto compare the data for malesand femalesyou must refer
to both for each comparison you make'

Fig 2. Smoking and lung cancer

30,000 4,500 30,000
tr 4,500 Women
o
a l<
L C)
4,000
8. 4,000 25,000
L
C)
25,000 t-
0-)

3,500
3 3,500 tr
()
c) >.
*- 20,000 l-1
b 3,000 (.) 3,000 CD

2.500
E 2,500
C) .t
0 JZ 15, 000
15,000
- CD
CD

a 2,000 (t
a
2,000 (D
a
c)
C! 0)
-
10,000
E r.soo
d
10,000
C)
l'

o0
1,500
.30 O

; 1.ooo (r 1,000
*r
5,000 t<
q)

-8 5oo - 500

z 0 0 Z
t991 l91l 1 9 3I 1951 l99l
1931 1951 t97 |
Year
Year

Key: Deaths Cigarettessmoked per personper year

Biologicalbasisof cancer
There is a clear correlation showing that as smoking became more
prevalent, due to changing fashions, so the number of deathsfrom lung
cancerincreased.while thesesfudiesweren't conclusive,when they were
repeatedfor other possiblecauses,such as atmosphericpollution, no such
correlationswere found.
Since these studies, experimentalevidencehas shown a direct causative
link befweenthe chemicalscontainedin cigarettesmoke and lung cancer.
It has been shown that the tar present in cigarettes contains polycyclic
hydrocarbon carcinogens,such as benzyprene and co-carcinogens. A
co-carcinogenis a substancethat increasesthe chancethat a carcinogen
will causechangesin DNA
Throughout both the developed and developing world, the number of
people smoking is still very high, despite the evidence of the risk to
health, not just of developing lung cancer, but also of developing
coronary heart disease,and of the increasedrisk of strokes.This has lead
to a huge strain on the health service, both financially and physically,
resulting in calls to prioritise treatment,with smokersbeing treatedafter
non-smokers,also the withholding of certain treatments,(such as heart
bypasssurgery), if the patient is still smoking.
Smoking and Lung Cancer
o The risk of developinglung cancerwill be higher if the smoker:
. Inhales
. Smokes high tar cigarettes
. Smokes for a long period of time
. once cancer is diagnosed,the choice of treatment depends on the site,
Smokes a large number of cigarettesa day
. nature and extent of the tumours. The main treatmentsare:
Starts smoking from a young age
. Smokes cigaretteswithout filters
o If smoking is stopped the risk decreases,but it takes over ten
years for the risk to return to the samelevel as a non-smoker
o One-third of all cancer-related deaths are a direct result of
cigarettesmoking
a Lung cancer is responsiblefor 25o/oof all deathsof smokers
o Smokers are nearly 20 times more likely to develop lung cancer
than non-smokers
Skin Cancers/Melanoma
Similar to lung cancer,there has been a link observedbetweenincreasing
levels of UV-radiation in sunlight and skin cancer. Over the years UV
levels have been increasing, due to the depletion of the ozone layer
causedby polluting CFCs used in refrigerators,aerosolpropellants and
foam expanders.The increasein UV-light intensity is linked directly to an
increasedincidence of skin cancer,although this trend is being reversed
to some extent by increasedpublic awarenessabout pollution and use of
sun lotions which 'filter out'the UV-light.
The skin pigment melanin provides some protection by absorbing the
radiation. Melanoma is a highly malignant tumour, which often forms
secondarytumours in the brain, resulting in death.
Exam Hint: The topic of UV-radiation and skin cancer often appears in
guesfbns relating to pollution,particularlyin synoptic guesflbnsand essays.
Diagnosis of cancer
The sooner cancer is diagnosedthe better the prognosis (likelihood of a
cure), therefore a lot of researchhas focusedon this aspectof cancer. As
a result there are a range of techniquesavailable,ranging from X-raying
the possibleaffected areasuch as the breast(mammography)or assessing
the area using imaging techniques such as ultrasound scanning,
Bio tactsbeet
rt,rttut.cu rriculum ss.co.uk
computerised tomography (CT) and magnetic resonance imaging
(MRI). The successof these techniquesrelies on the presenceof a
tumour that is large enough to be detected. others techniques involve
taking samples of body fluids, such as blood, and testing them
biochemically for abnormal products of cancer cells or histologically for
abnormal leucocytesin leukaemias.
More recently there have been advancesusing monoclonal antibodies,
which allow the diagnosis of cancers much earlier than the other
techniques. The advantage of using monoclonal antibodies is their
specific binding to antigenson the cancercells in question.For example,
leukaemiasand lymphomas are both cancersof white blood cells, which
are hard to distinguishbetween.The use of monoclonal antibodiesallows
the recognition of the different antigenson these cells. The monoclonal
antibodiesare taggedwith harmlessradioactive tracers (radionuclides)
which emit gamma-rays.As the tracer collects at clumps of cancer cells
it can be visualised by gamma scanning(not all types of gamma-ray are
dangerous).A three-dimensionalimage of the tumour and its position can
be built up and this enables radiotherapy treatment to be accurately
directed. A radionuclide in common use is technetium (*Tc). For thyroid
studies,radionuclidesof iodine (r25Iand ','I) are used,
Diagnostic techniqueslike this should enableearly diagnosisof common
cancers,such as breastand colon cancer,without taking samplesof body
fluids.
Treatment
. Surgery to remove the fumour
. Radiotherapy of the affected area using X-rays or y-rays to kill
tumour cells. Some tumours respondpoorly to this type of treatment
if they have low intemal oxygen levels. Becauseradiation has to be
precisely directed to the cancer, radiotherapy can only be used for
cancersthat are in discretetumour form and cannot be used asainst
dispersedcancercells.
. Chemotherapy of the whole body using chemicals which kill
dividing cells, including normal and tumour cells.
. Chemotherapy using drugs such as Tamoxifen, which reduces the
risk of developing of breasttumours by reducing oestrogenlevels as
high oestrogenlevels can stimulate the growth of breasttumours.
A natural means of defence against cancer is the immune system, and
research is being directed towards finding ways to stimulate immune
reactions,for example, by using interferons and interleukins produced
by genetically modified bacteria.
Radiotherapyand chemotherapyunfortunately kill some norrnal dividing
body cells as well as cancercells and so treatmentwith thesemethods has
unpleasantside effects, for example, hair loss and damage to the gut
lining. Fortunately the cancer cells are much more sensitive to the
treatmentsthan normal cells and so treatmentis still possible.
The use of monoclonal antibodies in diagnosis has already been
discussed,but they also have a potential role in the treatmentof cancers.
Anti-cancer drugs can be attachedto the antibody and thus delivered to
the desiredsite; theseare the so-calledmagic bullets.
Another technique is to tag monoclonal antibodies with an enzyme that
convertsthe inactive form (prodrug) of an anti-cancerdrug into an active
form. The prodrug is then administeredin high doses,but will only be
activatedat cancercells by the presenceof the enzyme,thus killing them,
while not having any effect on non-cancerouscells. This technique is
called ADEPT (Antibody Direct Enzyme Prodrug Therapy).
 Bio Factsbeet
Biologicalbasisof cancer w u,ra.c u rricu I u m P re ss.co. u k

Practice Questions Answers

1. (a) (i ) rapid fall of deathsper thousandfrom1.4 to 0.6inumber
l. The graphshowsthe deathrateper thousandof the populationfrom
andex-smokers.
luns cancerof non-smokers of deaths(more than) halve in first five years,
decreasesmore slowly in next 10 years from 0'6 to 0'2;
levels off at around 0.2 deathsper thousand;
J

named deposit take time to remove

(ii) carcinogens/deposits/
1.6
from lungs;
t.4
cancersalready presentdue to exposureto carclnogens
t.2 before stopping smoking;
1.0 lung damagedue to smoking takeslong time to rePair;
- ex-smokers max 2
0.8
0.6 (b) (i) more people smoke in developing countries;
a
0.4 fewer contols on industrialemissionsin developingcounffies;
q)
0.2 non-smokers L

0
5 1 0 1 5 2 0 (ii) in developing counffies people more likely to die of
time sincestoppingsmoking/years communicablediseases;
developedcountriespeople live longer so more likely to
die ofcancer;
(a) (i) Describethe pattern of the curve for ex-smokers. in developed countries better diagnosis of cancer as
3 causeof death; max 2

(ii) Suggesttwo reasonswhy it takes so many years for the 2 . oncogenesare activatedby carcinogens;
number of deaths to decrease to the lowest point' cancerouscell does not respondto signals from other cells;
a
L mitosis occurs;
cancerouscells are not removed by the immune system;
There are approximately 5.9 million new cancer casesin the world rapid mitosis occurs,
each year and I in 10 deaths is causedby cancer.The table below tumour gets bigger, cells changetheir appearanceand can be detected
shows somedifferencesbetweendevelopedand developingcounffies: under a microscoPe;
ref to migratory cells/tadpolecells;
Developed countries Developing countries tumour supplied with blood and lymph vessels;
tumour cells spreadin thesevesselsto other parts of the body;
Number of new
3.0 million ref to metastasis/cellsinvade other tissues;
cancercasesper year 2.9 million
secondarycancersform throughoutthe body;
Number of deaths due max l0
to cancerper year lin16
3. (a) (i) A carcinogenis an agentwhich can causethe development
of cancer; 1
Age range with highest
incidenceof cancer
(ii) benzyprene/polycyclichydrocarbons;
lulg cancer; 2

(b) Suggestan explanation for the difference between developed

(industrialised)countriesand developing countriesin: (iii) ultra-violetlight;
gf,[g cancer/melanomaixerodermapigmentosum;
2
(i) the age range with the gteatestincidence of cancer'
2
t31I'
(b) ref to radionuclides/technetium/eeTc'/iodine lt2slI
(ii) the deathsper year due to cancer' 2 taken up preferentially by cancercells/attachedto monoclonal
Total 9 antibodieswhich attachto cancercells;
emit harmless/softgammarays which can be imaged by a
gaffIma scanner/gammacamera;
2. Outline the sequenceof eventsin the formation of a secondarytumour'
Total 10 tumours can be directly inadiated with damaging radiation;
harmful,/hard X-rays or gamma-rays;
3. (a) (i) Define the term
'carcinogen'. 1 cancer cells more susceptibleto radiation damagethan normal cells;
max )

(ii) Name a chemical carcinogenand say which cancer it is

implicated to. 2

(iii) Name a non-ionising radiation and say which cancerit is Acknowledgements

implicated to. 2 This Factsheet was researched and written bv Fiona MacBain'
Bio Press.unit 3058, TheBig Peg, 120 VvseStreet,Birmingham BI8 6NF
their
Bio Factsheetsma.v-be copied free of charge bv teaching staJf or students,provided that
'Ionising radiationscan be used for diagnosisand for treatment stored in a
(b) school is a registered subscriber. No part of these Factsheets mav be reproduced,
prior
of cancer'. Explain this statement' 5 retrieval system, or transmitted, in anv other form or bv any other means, without the
Total 10 permissionofthe publisher ISSN I35l-5136