Lecture 1: Introduction
Big 5 > breast, squamous cell carcinoma (skin), lung, prostate, colon
In total, 216 different cancer types. 86% are rare (1 in 5 diagnosed per year has a rare cancer).
Lecture 2: Public health issues in oncology
Definition public health
= the science and art of preventing disease, prolonging life and promoting health through the
organized efforts of society.
o Health is a state of complete physical, mental and social well-being and the absence of
disease.
Public health vs medicine
Public health
o Population based
o Disease prevention
o Health promotion
o Interventions are environmental and human behavior (lifestyle, nutrient score, etc)
Medicine
o Focusses on individual patients
o Diagnosis
o Treatment
o Intervention is medical care
Application of public health
Population: from local areas to the world population (organize sports day in neighborhood to
promote physical activity).
Causes of disease: from behavior to broader environments (e.g. why someone starts smoking
can be dependent on the environment).
Prevention of disease: from individual patients to national policies (vaccination).
General health outcomes: form quality of life to healthy life expectancy.
3 fields of public health research
Epidemiology and community diagnosis
Collective prevention and health promotion
Health care organization and performance
Public health functions
Assessment and monitoring health
Formulation of policies
Focus on cos-effective care, etc.
Public health achievements
Since 1900: vaccination, safer workplaces, control of infectious diseases.
Since 1920: safer/healthier food, healthier mothers and babies, family planning.
Since 1965: fluoridation of drinking water, motor-vehicle safety, recognition of tobacco as a
health hazard, decline in deaths of CAD and stroke.
Biggest success in public health > improved sewage disposal and clean water.
,Global burden of cancer
Cancer is leading cause of death. Expected to rise enormously. 1 in 8 deaths worldwide.
o Getting older, earlier diagnostics, lifestyle, population is increasing.
Geographic variation
o Stomach cancer > 7x increased risk in Japan and Korea
o Breast & prostate > less in Asia, more in Caucasian people
o Melanoma > more in Australia and sunny parts
o Liver cancer more in south-east Asia and east Africa
o Thyroid cancer: deficiency of iodine in local food and water supplies (swiss alps)
Cancer prevention
Primary prevention
o Prevent people from getting the disease (e.g. healthier lifestyle)
o In cancer: HPV vaccination, encourage healthy lifesyle
Secondary prevention
o Try diagnosing in early stage of disease (e.g. mammograms, pap smear, etc)
o In cancer: screening for breast, cervical or colon cancer
Tertiary prevention
o Preventing the disease from getting worse or slow it down (e.g. relieving side effects
of chemo)
o In cancer: survivorship care (improve HRQoL), prevention cancer reoccurrence
How much of your cancer risk can be reduced by living healthy?
a. 20-25%
b. 30-35%
c. 40-45%
d. 50-55%
B > about a third.
How do we study risk factors
Cant do RCT. Do retrospective cohort or case-control study (basically same thing).
o End up with an WCRF matrix
How much variables are related to different kinds of cancer.
What lifestyle improvement will reduce your cancer risk the most?
a. Start being physically active
b. Stop consumption of alcohol
c. Overweight > healthy weight
d. Stop smoking
D
,Lecture 3: Introduction into oncology
Patient case
CT scan
o Black = lung
o White in the middle is heart
o White on the right corner (next to the heart) is a tumor
Biopsy is taken > diagnosis lung cancer.
PET-scan to be able to stage patient (how far has the cancer spread).
o Glucose taken in before the scan. Tracer accumulates in the tumor (takes it up) > can see
where exactly it is.
o See metastasis
What is cancer
Can arise in any cell of the body.
Cancer comprises a large group of diseases characterized by abnormal cells, which:
o Continuously proliferate
o Invades local tissue
o Can spread to other organs.
Difference benign and malignant
Benign does respect normal borders (even though it can grow quite big). Will never form
metastasis and wont kill you.
Malignant tumors have an irregular shape, do metastasize.
How many cancer cells are needed to form a tumor as big as a grape?
a. 10.000
b. 100.000
c. 1.000.000
d. 100.000.000
D
1.000.000 cancer cells > head of a pin
1.000.000.000 cancer cells > small grape.
Patient usually has had cancer for several years before it is detected or causes symptoms.
Types of cancer
Carcinoma (85%, most common)
o Squamous cell carcinoma
Comes from the lining (surface)
o Adenocarcinoma
Comes from glandular tissue (underneath the surface). Responds differently to
treatment
Sarcoma
o From bone and soft tissue
Glioma
o From glial cells in CNS (often brain tumors)
Melanoma
o From melanocytes in the skin
Leukemia
o From blood-forming tissue of the bone marrow
Lymphoma and myeloma
, o From lymph node tissue
How does cancer arise
DNA replication is complex and vulnerable to damage (especially by toxins (e.g. smoke,
asbestos)).
o Can be direct (due to the toxin) or indirect (increased cell replication)
o Can also have random errors
Normally cells repair the damage or undergo apoptosis
o Some cells survive
Types of genomic alterations
Point mutation > 2 bases switched around. Leads to different protein
Deletion > get smaller/shorter protein
Insertion > extra bases inserted into the DNA. Leads to larger protein
Translocation > DNA of 2 chromosomes are exchanged, leading to abnormal protein
Consequences of genomic alterations
Type and location of the alteration are important > determine the consequence.
2 types of genes that can be mutated
o Tumor suppressor gene (break system)
Normally block cell cycle progression
E.g. non-functional p53. Cant target it yet. See in almost all cancers.
Normally activated when there is DNA damage > binds > hold replication
process > DNA repair > if not work > cell suicide (so damage isn’t passed on)
E.g. tumor suppressor
BRCA1/2 > hereditary breast cancer
o (proto-)oncogene (accelerator)
Normally, codes for protein involved in cell growth
Mutation > more active protein > increased cell growth
Ras is on continuously (stimulates Raf, causing cell devision)
E.g. oncogenes
HER2 > breast cancer (can be targeted)
B-RAF and MEK > important in development melanoma (also can be targeted)
Hallmarks of cancer (multi-hit model) (first 3 most important)
Stimulate their own growth (self-sufficiency)
Resist inhibitory signal
Resist programmed cell death
Multiply indefinitely (limitless replicative potential)
Stimulate growth of new blood vessels (sustained angiogenesis)
Invade local tissue and metastasis
Abnormal metabolic pathways allow them to survive
Evade immune system
Show genome instability and mutation
Show tumor promoting inflammation
How many genes altered
In common solid tumors (e.g. colon, breast) > 33-66 genes display mutations
o Outliers > lung and melanoma (+-200 mutated genes).
Led to immunotherapy being used in these types (more foreign, easier to be
removed by immune system)
Big 5 > breast, squamous cell carcinoma (skin), lung, prostate, colon
In total, 216 different cancer types. 86% are rare (1 in 5 diagnosed per year has a rare cancer).
Lecture 2: Public health issues in oncology
Definition public health
= the science and art of preventing disease, prolonging life and promoting health through the
organized efforts of society.
o Health is a state of complete physical, mental and social well-being and the absence of
disease.
Public health vs medicine
Public health
o Population based
o Disease prevention
o Health promotion
o Interventions are environmental and human behavior (lifestyle, nutrient score, etc)
Medicine
o Focusses on individual patients
o Diagnosis
o Treatment
o Intervention is medical care
Application of public health
Population: from local areas to the world population (organize sports day in neighborhood to
promote physical activity).
Causes of disease: from behavior to broader environments (e.g. why someone starts smoking
can be dependent on the environment).
Prevention of disease: from individual patients to national policies (vaccination).
General health outcomes: form quality of life to healthy life expectancy.
3 fields of public health research
Epidemiology and community diagnosis
Collective prevention and health promotion
Health care organization and performance
Public health functions
Assessment and monitoring health
Formulation of policies
Focus on cos-effective care, etc.
Public health achievements
Since 1900: vaccination, safer workplaces, control of infectious diseases.
Since 1920: safer/healthier food, healthier mothers and babies, family planning.
Since 1965: fluoridation of drinking water, motor-vehicle safety, recognition of tobacco as a
health hazard, decline in deaths of CAD and stroke.
Biggest success in public health > improved sewage disposal and clean water.
,Global burden of cancer
Cancer is leading cause of death. Expected to rise enormously. 1 in 8 deaths worldwide.
o Getting older, earlier diagnostics, lifestyle, population is increasing.
Geographic variation
o Stomach cancer > 7x increased risk in Japan and Korea
o Breast & prostate > less in Asia, more in Caucasian people
o Melanoma > more in Australia and sunny parts
o Liver cancer more in south-east Asia and east Africa
o Thyroid cancer: deficiency of iodine in local food and water supplies (swiss alps)
Cancer prevention
Primary prevention
o Prevent people from getting the disease (e.g. healthier lifestyle)
o In cancer: HPV vaccination, encourage healthy lifesyle
Secondary prevention
o Try diagnosing in early stage of disease (e.g. mammograms, pap smear, etc)
o In cancer: screening for breast, cervical or colon cancer
Tertiary prevention
o Preventing the disease from getting worse or slow it down (e.g. relieving side effects
of chemo)
o In cancer: survivorship care (improve HRQoL), prevention cancer reoccurrence
How much of your cancer risk can be reduced by living healthy?
a. 20-25%
b. 30-35%
c. 40-45%
d. 50-55%
B > about a third.
How do we study risk factors
Cant do RCT. Do retrospective cohort or case-control study (basically same thing).
o End up with an WCRF matrix
How much variables are related to different kinds of cancer.
What lifestyle improvement will reduce your cancer risk the most?
a. Start being physically active
b. Stop consumption of alcohol
c. Overweight > healthy weight
d. Stop smoking
D
,Lecture 3: Introduction into oncology
Patient case
CT scan
o Black = lung
o White in the middle is heart
o White on the right corner (next to the heart) is a tumor
Biopsy is taken > diagnosis lung cancer.
PET-scan to be able to stage patient (how far has the cancer spread).
o Glucose taken in before the scan. Tracer accumulates in the tumor (takes it up) > can see
where exactly it is.
o See metastasis
What is cancer
Can arise in any cell of the body.
Cancer comprises a large group of diseases characterized by abnormal cells, which:
o Continuously proliferate
o Invades local tissue
o Can spread to other organs.
Difference benign and malignant
Benign does respect normal borders (even though it can grow quite big). Will never form
metastasis and wont kill you.
Malignant tumors have an irregular shape, do metastasize.
How many cancer cells are needed to form a tumor as big as a grape?
a. 10.000
b. 100.000
c. 1.000.000
d. 100.000.000
D
1.000.000 cancer cells > head of a pin
1.000.000.000 cancer cells > small grape.
Patient usually has had cancer for several years before it is detected or causes symptoms.
Types of cancer
Carcinoma (85%, most common)
o Squamous cell carcinoma
Comes from the lining (surface)
o Adenocarcinoma
Comes from glandular tissue (underneath the surface). Responds differently to
treatment
Sarcoma
o From bone and soft tissue
Glioma
o From glial cells in CNS (often brain tumors)
Melanoma
o From melanocytes in the skin
Leukemia
o From blood-forming tissue of the bone marrow
Lymphoma and myeloma
, o From lymph node tissue
How does cancer arise
DNA replication is complex and vulnerable to damage (especially by toxins (e.g. smoke,
asbestos)).
o Can be direct (due to the toxin) or indirect (increased cell replication)
o Can also have random errors
Normally cells repair the damage or undergo apoptosis
o Some cells survive
Types of genomic alterations
Point mutation > 2 bases switched around. Leads to different protein
Deletion > get smaller/shorter protein
Insertion > extra bases inserted into the DNA. Leads to larger protein
Translocation > DNA of 2 chromosomes are exchanged, leading to abnormal protein
Consequences of genomic alterations
Type and location of the alteration are important > determine the consequence.
2 types of genes that can be mutated
o Tumor suppressor gene (break system)
Normally block cell cycle progression
E.g. non-functional p53. Cant target it yet. See in almost all cancers.
Normally activated when there is DNA damage > binds > hold replication
process > DNA repair > if not work > cell suicide (so damage isn’t passed on)
E.g. tumor suppressor
BRCA1/2 > hereditary breast cancer
o (proto-)oncogene (accelerator)
Normally, codes for protein involved in cell growth
Mutation > more active protein > increased cell growth
Ras is on continuously (stimulates Raf, causing cell devision)
E.g. oncogenes
HER2 > breast cancer (can be targeted)
B-RAF and MEK > important in development melanoma (also can be targeted)
Hallmarks of cancer (multi-hit model) (first 3 most important)
Stimulate their own growth (self-sufficiency)
Resist inhibitory signal
Resist programmed cell death
Multiply indefinitely (limitless replicative potential)
Stimulate growth of new blood vessels (sustained angiogenesis)
Invade local tissue and metastasis
Abnormal metabolic pathways allow them to survive
Evade immune system
Show genome instability and mutation
Show tumor promoting inflammation
How many genes altered
In common solid tumors (e.g. colon, breast) > 33-66 genes display mutations
o Outliers > lung and melanoma (+-200 mutated genes).
Led to immunotherapy being used in these types (more foreign, easier to be
removed by immune system)
