All lectures of the master course oncology (NWI-BM015c) are covered in the document (using the powerpoint slides and additional information covered in the lectures). The figures included are taken from the PowerPoint slides. All processes and concepts discussed are extensively described using examp...
Oncology lectures
Lecture 1: epidemiological aspects of tumours
Descriptive epidemiology
The life-time risk (85 years) of cancer in females is about 38% percent. In males this risk is about 45%.
This because the cancer types and women differ, but also the lifestyle factors they are exposed to are
different. An example is smoking, which used to be more common in males.
- Breast cancer is the most common cancer type in females, prostate cancer is the most
common cancer type in males.
Cancer epidemiology is important because it helps to gain knowledge about trends in incidence,
survival, and mortality of cancer. This can help to make informed decisions regarding health policy.
Epidemiology can also be used adequate evaluation of clinical developments.
The key epidemiological concepts are the following:
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑒𝑜𝑝𝑙𝑒 𝑤𝑖𝑡ℎ 𝑐𝑎𝑛𝑐𝑒𝑟
- Prevalence: 𝑝𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 𝑎𝑡 𝑟𝑖𝑠𝑘
.
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑛𝑒𝑤𝑙𝑦 𝑑𝑖𝑎𝑔𝑛𝑜𝑠𝑒𝑑 𝑐𝑎𝑠𝑒𝑠 𝑜𝑓 𝑐𝑎𝑛𝑐𝑒𝑟
- Incidence: .
𝑝𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 𝑎𝑡 𝑟𝑖𝑠𝑘
Incidence can be expressed in different formulas:
o CR (crude rate): number of new cases/100.000 persons/year.
o ESR (European standardized rate): number of new cases/100.000 persons/year
standardized for the age composition of Europe.
o WSR (world standardized rate): number of new cases/100.000 persons/year
standardized for the age composition of the world.
These different formulas of calculating incidence make it possible to notice differences in
cancer prevalence between countries.
The population of risk can be defined by a certain age group. Therefore, the population at risk may
be different for the different calculations.
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑎𝑠𝑒𝑠 𝑡ℎ𝑎𝑡 𝑑𝑖𝑒𝑑 𝑓𝑟𝑜𝑚 𝑐𝑎𝑛𝑐𝑒𝑟
- Mortality: .
𝑝𝑜𝑝𝑢𝑙𝑎𝑡𝑖𝑜𝑛 𝑎𝑡 𝑟𝑖𝑠𝑘
The mortality is expressed as CR, ESR, and WSR as well.
- Relative survival: the percentage of cancer cases alive at a certain time period after
diagnosis. This number does not include those who died from other diseases.
There are worldwide differences in cancer incidence. There is especially high incidence in cancer
cases in western countries, which can be related to lifestyle, e.g. BMI is an important risk factor for
cancer.
Worldwide differences
The incidence of different cancer types differs per country. For example, stomach cancer is mostly
common in Asian and South-American countries. In these countries infections with the Helicobacter
pylori are much more common, which is a great risk factor. Also, the food conservation is very
different in Asian countries, e.g. fish is conserved with the help of salt, which is associated with a
higher risk of stomach cancer.
Liver cancer is most prevalent in China and some African countries. This because hepatitis B infection
is more common in these countries. Also, when peanuts are stored under mouldy circumstances the
substance aflatoxin develops → people in these countries are exposed more to aflatoxin, which is a
risk factor.
,Cervix cancer is most common in African countries, which is due to the Human Papillomavirus (HPV),
which is an important risk factor for getting cervix cancer. HPV is more present in this part of the
world, and the screening procedure for cervical cancer is less organized.
In the Netherlands about 118,000 people/year are diagnosed with cancer. The last years the
incidence of incidence has been increasing. In the Netherlands, the most frequent cancer types are
the following:
- Man: prostate, skin, colorectal, lung.
- Woman: breast, skin, colorectal, lung.
The ESR standardized rate of lung cancer shows a decrease in the incidence of lung cancer in man
(less smoking) while there is an increase of lung cancer in woman (more smoking).
The mortality of cancer in the Netherlands is also increasing over the years, although the relative
mortality is decreasing. Lung cancer is the cancer with the highest mortality rate in both men and
women. The relative survival changes with age and cancer stage.
Etiology
The most important risk factor for cancer in general is age. The development of mutations takes
time. Mutations can be either spontaneous, or after exposure to chemical substances, radiation, or
viruses. Mutations need to accumulate in the daughter cells before cancer will develop. Older people
have been exposed to more risk factors, and therefore have a higher change of cancer development.
The body has several protective tools to help prevent cancer formation:
- DNA repair.
- Apoptosis.
- Senescence (mitosis stops).
However, at an older age there is accumulation of damage and mutations in regulatory genes.
Because of this damage the repair tools are less effective and there is less control by the
microenvironment.
- For most cancers, alterations start after age forty.
Over the past hundred years, the life expectancy in the Netherlands has dramatically increased.
Therefore, the number of older people has increased, which leads to “grey pressure”: the number of
old people relative to the number of young people is increasing. The consequence of this is an
increase in the number of cancer diagnoses per year. However, the survival rates of cancer are
improving as well → there is a higher incidence, but also a higher survival.
Cancer is an enormous public health problem, and the double aging phenomenon (people are getting
older, and there are more older people) only enhances this. There is better survival because of
improved treatment and early detection, but this also leads to more expensive health care.
Therefore, cancer prevention is very important.
The incidence of in very old people (>80) decreases. Explanations might that these people already
survived for a long time without cancer, meaning that they have lower genetic susceptibility to
cancer. They also have a lower cell division, and higher senescence → more protected against
cancer. Furthermore, cancer might be more undetected in older people (they undergo less
screening).
Identifying causes of cancer
1. Accidental finding.
, 2. Systematic counting.
3. Focussed research, human observational, model experimental.
4. Exploration.
Accidental finding
Some examples of accidental findings:
- High incidence of breast cancer in nuns. This was the first idea that hormones might be
related to breast cancer.
- High incidence of skin lesions and leukaemia in doctors working with radiation. Also, women
who were suffering from tuberculosis and therefore receiving many x-rays, had a higher risk
of breast cancer.
- Watch painters used radium to paint the numbers on the watch. The women put the radium
containing brushes in their mouths and showed with higher cases of tumours in their mouth
and throat. These women also showed many cases of bone cancer and leukaemia.
Systematic counting
Some examples of systematic counting:
- A doctor investigated retinoblastoma. Some children developed this in both eyes, others only
in one eye. After investigation of these children, the two-hit model was invented: the
children with retinoblastoma in two eyes often had hereditary mutations, while the
retinoblastomas in one eye often were not hereditary.
- Stomach cancer is more common in Asian countries. To investigate the relation of lifestyle
and cancer, people who grew up in Japan and immigrated to the USA were followed. People
who grew up in Japan had high incidence in stomach cancer, but the first generation of
offspring already had a lower change of getting stomach cancer, although their changes were
still higher than other US inhabitants. Whereas for breast cancer, which is more common in
the US than Japan, it was shown that over the first and second generation of offspring the
changes of getting breast cancer increased. It is likely that lifestyle plays a high role in this.
- In the 1970s the incidence of melanoma increased → in this period sunbathing started to
become more popular. After sunscreen became more available, the incident of melanomas
dropped again.
Focussed research
A possibility is a case-control study. In
this study, you start with the cases, for
example women with breast cancer. The
control group consists of women without
the disease. Investigation often goes via a
questionnaire; ask the subject whether
they have been exposed to specific
environmental things (e.g. smoking,
certain diets, alcohol consumption, etc).
It can be checked whether the exposure
differs between the cases and controls. The limitation of this is that the cases might remember this
better than the controls.
- One of the earlies case-control studies was done by a gynaecologist. He observed many
young women with squamous adenoma carcinomas in the cervix, where this is normally
observed in older women. The mothers of the women were questioned about intrauterine
exposure. He investigated anti-depressives, x-rays, smoking, and miscarriages. It was shown
that the mothers of the young women with cervical cancer used oestrogens during their
pregnancy to prevent miscarriage → desdochters.
, Another option of focussed research is the
prospective cohort study. In this study, you
start with a certain population and
investigate who has been exposed to certain
factors, and who has not → e.g. comparing
smokers and non-smokers. Within this group,
investigate whether the incidence of disease
is different between the exposed and non-
exposed group. The advantage above case-
control studies is that the questionnaire is
taken before disease development → no bias
between disease and non-disease group.
- On of the first cohort studies was a
study showing the relation between
smoking and cancer. The study showed that half of cigarette smokers would be either killed
by cancer or heart disease. Smoking is an important risk factor for cancer: 95% of lung
cancer, 50% of bladder cancer, stomach cancer, intestine cancer, etc. are all influenced by
smoking. Several substances in cigarette smoke can induce mutations which eventually lead
to (lung) cancer.
Cancer prevention
33% of cancers can be prevented by a healthy diet, healthy body weight, and physical activity. This
however depends on cancer type:
- Colorectal cancer: 50% can be prevented by a healthy lifestyle because the colon is
continuously exposed to the ingested food.
This was investigated through a systematic literature review.
𝑝(𝑅𝑅−1)
To calculate the population attributable (preventable) fraction (PAF): 𝑝(𝑅𝑅−1)+1. In this formulate, RR
is the relative risk of disease for the risk factor, and p is the prevalence (proportion) of the risk factor
in the population.
Obesity is related to different
cancer types. There are different
reasons for this association:
- More inflammatory
factors.
- Higher exposure to
hormone levels.
- Higher exposure to
different types of growth
factors.
Sufficient physical activity is
protective for cancer, mostly
endometrial cancer, breast
cancer, and colorectal cancer.
A reason can be, that more
physical activity lowers the risk of
being overweight. But physical
activity itself has an effect on
oestrogen levels and
inflammation markers →
decreasing the risk of cancer.
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