Cancer: causes and treatment

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Cancer causes and treatment
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Causes of mutations

• Replication errors
• Exacerbated by poor DNA repair
• Other biological agents
• Viruses
• Transposons
• Environmental factors
• Ultraviolet light
• Mutagenic chemicals
• smoking, industrial waste, natural toxins

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Change in the US Death Rates by Cause, 1950
2000
Rate Per 100,000
1950 2000
Cancer
HeartDiseases
Pneumonia/Influenza
Stroke
Age-adjusted to the 2000 US standard
population. Source US Mortality Volume 1950,
National Vital Statistics Report, 2002, Vol. 50,
No. 15.
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Cancer Death Rates, for Men, US, 1930-1999
Rate Per 100,000
Lung
Stomach
Prostate
Colon and rectum
Pancreas
Liver
Leukemia
Age-adjusted to the 2000 US standard
population. Source US Mortality Public Use Data
Tapes 1960-1999, US Mortality Volumes 1930-1959,
National Center for Health
Statistics, Centers for Disease Control and
Prevention, 2002.
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Cancer Death Rates, for Women, US, 1930-1999
Rate Per 100,000
Lung
Uterus
Breast
Colon and rectum
Stomach
Ovary
Pancreas
Age-adjusted to the 2000 US standard
population. Source US Mortality Public Use Data
Tapes 1960-1999, US Mortality Volumes 1930-1959,
National Center for Health
Statistics, Centers for Disease Control and
Prevention, 2002.
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Treating cancer

• Avoid it
• Avoid mutagens
• DNA repair gets less efficient as we age

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Our immune system protects us from cancer
T-cells recognize and eliminate abnormal cells
such as cells with many mutations
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Treating cancer

• Avoid it
• Avoid mutagens
• DNA repair gets less efficient as we age
• Surgery
• Must remove all cancer cells
• Non-invasive

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Treating cancer

• Avoid it
• Avoid mutagens
• DNA repair gets less efficient as we age
• Surgery
• Must remove all cancer cells
• Non-invasive
• Radiation
• Directed at tumor causes DNA damage
• -gt cellular self-destruction
• Mutagenic, side effects

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Treating cancer

• Avoid it
• Avoid mutagens
• DNA repair gets less efficient as we age
• Surgery
• Must remove all cancer cells
• Non-invasive
• Radiation
• Directed at tumor
• Mutagenic, side effects
• Chemotherapy
• Toxins directed at rapidly dividing cells
• Mutagenic, many side effects

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Chemotherapy
Toxin
X
X
a rapidly dividing cell
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Normal Multi-Drug Resistance protein
toxin/hormone/etc
MDR
toxin/hormone/etc
toxin/hormone/etc
MDR
MDR
MDR
toxin/hormone/etc
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Some cancers over-express MDR
toxin
toxin
toxin
toxin
Toxin
MDR
MDR
MDR
MDR
Im a cancer cell with over-expressing MDR. I
laugh at your toxins.
toxin
MDR
toxin
MDR
toxin
toxin
MDR
MDR
MDR
MDR
MDR
MDR
toxin
toxin
toxin
toxin
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Mutations continue after cancer develops
The Epigenetic Progenitor Origin of Human Cancer
(2007) A P Feinberg, R Ohlsson, S Henikoff
Nature Reviews Genetics 7 21-31
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Evolution changes in DNA as information
transmitted
O
O
O
Cancer cell with mutation causing MDR
over-production
O
O
O
O
O
O
O
O
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Evolution changes in DNA as information
transmitted
O
O
O
Cancer cell with mutation causing MDR
over-production
O
O
O
O
O
O
O
O
Apply chemotherapy
X
X
X
O
O
O
X
X
X
O
O
O
O
X
X
X
X
O
O
O
O
Kills most cells. Except if some have mutation
that allow them to be resistant.
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Evolution changes in DNA as information
transmitted
O
O
O
Cancer cell with mutation causing MDR
over-production
O
O
O
O
O
O
O
O
Apply chemotherapy
Continues to replicate
O
X
X
X
O
O
O
X
X
X
O
O
O
O
X
X
X
X
O
O
O
O
Kills most cells. Except if some have mutation
that allow them to be resistant.
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Evolution changes in DNA as information
transmitted
O
O
O
Cancer cell with mutation causing MDR
over-production
O
O
O
O
O
O
O
O
Apply chemotherapy
Continues to replicate
O
X
X
X
O
O
O
O
O
O
X
X
X
O
O
O
O
O
O
O
O
X
X
X
X
O
O
O
O
Kills most cells.
O
O
O
O
Tumor with cells expressing MDR
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Some cancers over-express MDR
toxin
toxin
toxin
toxin
Toxin
MDR
MDR
MDR
MDR
Im a cancer cell with over-expressing MDR. I
laugh at your toxins.
toxin
MDR
toxin
MDR
toxin
toxin
MDR
MDR
MDR
MDR
MDR
MDR
toxin
toxin
toxin
toxin
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Treating cancer

• Avoid it
• Avoid mutagens
• DNA repair gets less efficient as we age
• Surgery
• Must remove all cancer cells
• Non-invasive
• Radiation
• Directed at tumor
• Mutagenic, side effects
• Chemotherapy
• Toxins directed at rapidly dividing cells
• Mutagenic, many side effects

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CB18.22
Multiple mutations are required for a single cell
to become cancerous.
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How can mutations be minimized?
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Telomeres are non-gene DNA at the ends of DNA
strands.
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Telomeres are non-gene DNA at the ends of DNA
strands.
Telomeres are shortened during DNA replication.
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Telomeres are non-gene DNA at the ends of DNA
strands.
Telomeres are shortened during DNA replication,
and also by DNA damage.
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Telomeres are non-gene DNA at the ends of DNA
strands.
Short telomeres will cause cells to stop
replicating or cell death. The critical size is
unknown.
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Human Life Cycle
high levels of telomerase
very little telomerase
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Why not produce telomerase all of the time?
high levels of telomerase
very little telomerase
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Telomeres are non-gene DNA at the ends of DNA
strands.
Telomeres are shortened during DNA replication,
and by DNA damage. Short telomeres will cause
cell senescence or cell death. Telomere size is
an indirect measure of mutations.
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Balance between Longevity and Health
Fig. 3 TRENDS in Ecology and Evolution Vol 21 pg
47
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Do telomere dynamics link lifestyle and
lifespan? Pat Monaghan and Mark F.
Haussmann TRENDS in Ecology and EvolutionVol 21
pg 47
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Telomere length varies in different parts of
adults telomeres - mitosisstomach blood
cells....short - often
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Telomere length varies in different parts of
adults telomeres - mitosisstomach blood
cells....short - often muscle brain.long -
rare
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Telomere length varies in different parts of
adults telomeres - mitosisstomach blood
cells....short - often muscle brain.long -
rare liver kidney..short - rare
40
Telomere length varies in different parts of
adults telomeres - mitosisstomach blood
cells....short - often muscle brain.long -
rare liver kidney..short - rare gameteslong
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Telomere length in red blood cells of different
birds
Zebra finch
Age (years)
Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg
47
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Telomere length in red blood cells of different
birds
common tern
Age (years)
Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg
47
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Telomere length in red blood cells of different
birds
albatross
TRENDS in Ecology and Evolution Vol 21 pg 47
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Telomere length in red blood cells of different
birds
Leachs storm petrel
Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg
47
45
Telomere length in red blood cells of different
birds, different species have different patterns
of telomere length and age
Zebra finch
common tern
albatross
Leachs storm petrel
Fig. 1 TRENDS in Ecology and Evolution Vol 21 pg
47
46
Telomere length in white blood cells of different
aged people. Telomere length generally declines,
but there is wide variability
Fig. 2 TRENDS in Ecology and Evolution Vol 21 pg
47
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Telomeres are non-gene DNA at the ends of DNA
strands.
Telomeres are more sensitive to DNA damage, and
may act as a sensor for overall DNA damage levels
in a cell.
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Does telomere length indicate longevity?
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Telomere length and mortality in people over 60
years old
proportion surviving
upper 50 of telomere length
lower 50 of telomere length
years after initial assessment
THE LANCET Vol 361 pg 393
50
Telomere length may indicate biological
age. Early stress may cause premature telomere
degradation.
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Balance between Longevity and Health
Fig. 3 TRENDS in Ecology and Evolution Vol 21 pg
47
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