Oncology introduction
10-11-2023
General remarks:
- Clinical oriented course
- No recordings?
- Process of accumulations of genetic alterations …
- Hallmarks of cancer: The circle with colors
- Cancer is a multi-step process
o Normal, initiation and promotion, progression, advanced cancer
- Exam
o Open questions
o One per topic
o Just like stem cell biology
- 9 lectures
- Interactive lectures
,LE1 - Epidemiological aspects of
tumors
10-11-2023
General remarks: Why this part?
- Kidney cancer
- Bladder cancer
- Etiology how does cancer develop?
- Know about trends in incidence and survival/ mortality after cancer
- Can be used to develop effective policies for cancer control.
Risks:
- Lifetime risk is important in cancer development Male 45% chance to develop cancer,
female 38% to develop cancer.
- Age is the highest risk factor for cancer development.--> time is necessary to accumulate
damage and mutations to develop cancer.
o Mutations in regulatory genes: Spontaneous, Chemical substances, radiation, viruses.
o Accumulation of damage / mutations in regulatory genes
o More damage to repair tools / repair tools less effective
o Less control by micro-environment
- Stomach cancer helicobacter pylori increases the risk of stomach cancer in Asia. Also food
conservation (pickled, salt) more prevalent in Asia. Very bad for the stomach.
- Liver cancer hepatitis B, Aflatoxin (mold on peanuts).
- Cervix cancer African countries, HPV more common.
- Male prostate cancer
- Female breast cancer
- Cancer risk obesity
- Physical activity reduces the risk for cancer development.
- Alcohol risk factor for cancer. Ethanol acetaldehyde DNA damage cancer.
- Red meat not sure if it is a real risk factor, not really randomized trial can be performed,
ethical.
Key epidemiological concepts:
- Prevalence number of people with cancer/ population at risk. At a certain moment in
time.
- Incidence Number of newly diagnosed cases of cancer/ population at risk. In a certain time
period.
o Incidence can be measured in various rates:
o • Number:
absolute number of new cases in a certain period
o • CR (crude rate):
number of new cases per 100,000 persons per year
o • ESR (European standardized rate):
number of new cases per 100,000 persons per year,
standardized for the age composition of Europe
o • WSR (World standardized rate):
number of new cases per 100,000 persons per year,
standardized for the age composition of the world
, - Mortality Number of cases that died from cancer/ population at riks. In a certain time
period.
- Relative survival % of cancer cases alive/ % of people of same age and sex expected to be
alive in the general population.
Grey pressure: Number 65+ age/ number 20-64 age
Public health problem: Double ageing phenomenon.
Better survival because of early detection, improved treatment.
More expensive health care Diagnosis, treatment
So focus on prevention!!
How do you identify (new) causes of cancer:
- Accidental finding / keep alert
o Radiation
o Tata steel
o Brush radiant paint
- Systematic counting / trends
o Retinoblastoma, difference between 1 eye and 2 eyes affected and its correlation to
cancer development.
o Migrant studies, from Japan to America and other way around, found that countries
affect cancer types prevalence.
o Trend in melanomas.
- Focused research human observational studies, experimental studies
o Case-control study Take a number of cases with a type of disease, compare to
control group, then compare the exposure between the cases and controls. This way
you can see if smoking is a risk factor with the disease. Also adenocarcinoma in
vagina case, in which miscarriage appeared in the mothers of the patients before the
daughter was born, so estrogens were taken and affected development. After disease
and trace back.
o Cohort study Questionnaires. Defined population Exposed, not exposed and
then see if the development of the disease or no disease over time. Before disease
experiment.
o Tabacco contains many carcinogens.
- Exploration
o GWAS: Genome sequencing: Genotyping, imputation, association statistics, meta-
analysis.
Diet and lifestyle with cancer risk development:
- Healthy life style can prevent 33% of cancer types.
Grading the evidence
- Convincing
- Probable
- Strong evidence: basis for recommendations
Limited evidence:
- Limited evidence- suggestive
- Limited evidence – No conclusion
- Substantial effect on risk unlikely
, Grading the evidence Convincing:
- Strong and unlikely to change in future
- No unexplained heterogeneity
- At least 2 independent cohort studies
- Good quality studies that account for error
- Dose response
- Robust evidence from laboratory studies
Grading the evidence Probable:
- No unexplained heterogeneity
- At least 2 independent cohort or 5 case-control studies
- Good quality studies that account for error
- Dose response
- Plausible evidence from laboratory studie
Case-Control Studies: outcome is known
Definition: In a case-control study, researchers start with individuals who have a certain outcome or
condition (cases) and compare them with individuals who do not have the outcome or condition
(controls). The goal is to identify factors that may have contributed to the development of the
condition.
Differences: The key characteristic is that it's retrospective, meaning researchers look back in time to
analyze and compare data. It's efficient for studying rare conditions or diseases, but causation can be
challenging to establish.
Prospective Cohort Studies: outcome is not known
Definition: In a prospective cohort study, researchers identify a group of individuals without the
outcome of interest and follow them over time to observe the development of the outcome. They
collect data on exposure factors and look for associations between these factors and the
development of the condition.
Differences: This study design is forward-looking, starting with a group of healthy individuals and
tracking them into the future. It's effective for establishing causation and understanding the natural
history of a condition. However, it can be resource-intensive and time-consuming.
Randomized Controlled Trials (RCTs): finding a treatment
Definition: In randomized controlled trials, participants are randomly assigned to different groups,
including an experimental group that receives the intervention being tested and a control group that
does not. This randomization helps control for confounding variables and allows researchers to assess
the impact of the intervention.
Differences: RCTs are experimental studies, often considered the gold standard for establishing
causation. They provide a high level of control over variables, helping to isolate the effects of the
intervention. Random assignment helps minimize bias and allows for statistical comparisons.
Population attributable (preventable) fraction (PAF)
- PAF = p(RR-1) / p(RR – 1) + 1
- Prevalence of the risk factors in the population (p)
- Relative risk of disease for the risk factors (RR)
Physical activity and cancer; RR for high vs low
- Physical activity reduces the risk for cancer development.
