Download LESSON 1.5 WORKBOOK How do we determine cancer risk?

LESSON 1.5 WORKBOOK
How do we determine cancer risk?
DEFINITIONS OF TERMS
Risk factor – any agent that
increases the chance that someone will develop a disease.
For a complete list of defined
terms, see the Glossary.
The last lesson focused on how hard it is to definitively prove that a suspected
carcinogen actually causes cancer. This lesson looks at cancer from a different
perspective – how can we assess whether a specific behavior - like smoking
– increases the risk of developing cancer? Understanding how to assess risk is
critically important since it is clear that identifying a behavior as risky and then
eliminating it can be equivalent to avoiding a cancer-causing agent.
What are the major risk factors for cancer?
The previous lesson discussed how difficult it is to definitively prove that a substance is carcinogenic.
Because of these challenges most suspected carcinogens can only be categorized as risk factors. A risk
factor being any agent that increases the chance that someone will develop cancer. As seen in Figure 1,
the major risk factors of cancer are:
■■ Diet
■■ Tobacco
■■ Infections
■■ Obesity
■■ Others (Hormones, pollution, and radiation)
■■ Alcohol
■■ Genetics
Wo r k b o o k
Lesson 1.5
Surprisingly diet is the major risk factor for cancer, with
between 30-35% of all cancer being linked to diet. Diet
increases the risk of developing cancer directly and
indirectly: Directly, diets that are rich in red meats and
processed meats, and high in salt directly increase the
Figure 1: 95% of all cancers are caused
by environmental agents, chiefly diet and
smoking.
MC Questions:
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1. Which of the following is NOT a
major risk factor for cancer?
aa. Genetics;
bb. Infections;
cc. Tobacco products;
dd. Obesity.
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LESSON READINGS
risk of cancers of the digestive system: mouth, esophageal, stomach and bowel cancer. Conversely diets
rich in fruits, vegetables and fiber actually decrease the risk of these cancers. Diet plays an indirect role
in cancer by promoting obesity. Obesity in turn is often associated with abnormal hormone levels, which
also constitute a cancer risk.
It is estimated that 25-30% of all cancers are caused by smoking or exposure to tobacco smoke. While
we covered the link between tobacco and lung cancer in the previous lesson it is important to note that
smoking is a risk factor in a number of different cancers as well as lung cancer, the most prevalent being
mouth, esophagus, stomach, breast, and colon.
DEFINITIONS OF TERMS
Obesity – A medical condition
due to accumulation of excess fat
that can reduce life expectancy.
Hormone – an internal signal in
the bloodstream that regulates
cell and tissue growth and development.
Estrogen-like compounds –
chemicals that are commonly
found in plastics and that behave
like the hormone estrogen. A risk
factor for cancer.
Wo r k b o o k
Lesson 1.5
Infections are also responsible for causing 15-20% of all cancers; many different types are involved including stomach cancer, which is caused by the bacteria Helicobacter pylori, liver cancer which is caused by
Hepatitis B and C viruses (as well as the liver fluke parasite), and cervical and some oral cancers which
are caused by Human papillomavirus (HPV). Fortunately antibiotics against H. pylori and the liver fluke,
vaccines for HPV and Hepatiits B, and drugs to treat Hepatitis C all reduce the mortality associated with
these cancers.
Other environmental agents that promote cancer include hormones, pollution, and radiation. Chemicals
found in plastics behave like estrogen, a hormone that regulates cell growth. Overexposure to estrogen
promotes the risk of developing cancer. Pollution from coal, soot, and asbestos, typically from occupational exposure are cancer risk factors. Radiation exposure most typically occurs in the form of UV radiation
from the sun but may also be linked to occupational exposure.
Excessive alcohol intake is associated with increased risk of liver and
pancreatic cancer
To understand why the role of genetic inheritance in cancer risk is relatively small we need to consider
the two things that must have occurred to put the risk in place: First the DNA sequence of an important
gene, like a growth factor, must have been mutated in a specific way so as to interrupt its function.
Second that mutation must have occurred in the DNA of germ cells such as eggs and sperm so that the
mutation can be inherited. Nonetheless risk can be inherited: As we saw in lesson 1.3 mutations in the
retinoblastoma gene called Rb predispose to developing cancer of the retina of the eye (retinoblastoma)
as well as other types of cancers. Similarly, mutations in the BRCA1 gene predispose to risk for
developing breast, ovarian, prostate and pancreatic cancers. These issues will be addressed again in Unit
3.
MC Questions:
2. How is diet a risk factor for cancer?
(Circle all correct.)
aa. Diet can lead to obesity, which
promotes cancer.
bb. High meat diets increase cancer
risk.
cc. High fiber diets increase cancer
risk.
dd. Consumption of foods
containing estrogen-like
compounds can promote cancer.
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LESSON READINGS
As we saw in the last lesson, the ambiguities around causation as it relates to complex diseases like
cancer mean that it is usually not possible to determine unequivocally whether an agent truly “causes”
cancer. In contrast, establishing the risk associated with exposure to the suspected agent is much clearer.
Hill’s postulates don’t allow us to definitively prove whether or not cell phones cause brain cancer, but we
can easily calculate whether using cell phones increases the risk of developing brain cancer.
The ability to calculate whether a certain agent increases the risk of developing cancer allows us to start
to address critical questions such as: “What can I avoid in order to prevent cancer?”
DEFINITIONS OF TERMS
Relative risk – The extent to
which a risk factor is responsible
for causing disease in a population
Risk is generally calculated in one of two ways – as relative risk and as the odds ratio. They both
depend on the same concept – namely the likelihood that exposure to an agent will lead to disease.
The calculations are best understood using a simple example. The question being investigated is:
‘Does exposure to asbestos increase the risk of developing lung cancer?’. The researchers assembled
a population of people, some of whom were exposed to asbestos, some of whom weren’t. Then they
observed the population to figure out who developed lung cancer and who didn’t. The numbers are in
the table below. Even without a calculation it is evident that while the numbers of people who developed
lung cancer were similar, whether they were exposed to asbestos or not, the proportion of people who
developed lung cancer after asbestos exposure was much higher (1 in 1.6) compared with the group that
wasn’t exposed (1 in 7.6) Take a minute to make sure you understand how we got these numbers. Now
let’s use them to calculate relative risk:
Exposed to Asbestos
Odds ratio – The odds of a disease appearing in the population
after exposure to a risk factor.
Wo r k b o o k
Lesson 1.5
Not Exposed to Asbestos
Total
Lung Cancer
10
13
23
No Lung Cancer
152
747
899
Total
169
760
922
Relative Risk = (Exposed with lung cancer/Total Exposed) / (Not exposed with lung cancer/Total not
exposed)
Relative Risk = (10 / 162) / (13 / 760)
Relative Risk = 0.0617 / 0.0171
Relative Risk = 3.6
MC Questions:
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3. True or false: Relative risk is a
distinct calculation from odds ratio
and it is important to know the
difference between the two.
aa. True.
bb. False.
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LESSON READINGS
Another way to look at risk is with the odds ratio. Instead of comparing the people who got lung cancer
with the total in each group, it compares the people who got lung cancer in each group with the people
who didn’t get lung cancer in each group. Not surprisingly the numbers are slightly different:
Odds ratio =
(Exposed with cancer/Exposed and No cancer) / (Not exposed with cancer/Not exposed and no cancer)
Odds ratio = (10/152) / (13/747)
Odds ratio = 0.0657 / 0.0174
Odds ratio = 3.8
DEFINITIONS OF TERMS
Five-year survival rate – the
percent of people diagnosed with
the disease who are still alive
after five years.
Although both calculations are used for calculating risk, the relative risk is preferred over the odds ratio in
clinical studies, such as estimating cancer risk. This is because the odds ratio over-estimates risk unless
the disease is rare (you can substitute your own figures into the calculation to prove this point). Since the
definition of ‘rare’ is very subjective using the relative risk removes that concern.
But what does the number mean? If the relative risk or odds ratio is above 1, exposure to asbestos has
increased the risk of developing cancer. If the relative risk or odds ratio is 1, or close to 1 there is no
relationship between exposure to asbestos and cancer. But if the relative risk or odds ratio is below 1
exposure has actually protected against cancer. This clearly would not happen for asbestos, but for eating
fruits and vegetables the odds ratio of developing lung cancer is only 0.4, all other things being equal.
An asbestos worker might be tempted to think that (s)he could reduce their risk of developing lung cancer
by eating a healthier diet, but risk calculations can’t simply be added together in this way. While it is
certainly possible and often critically important to take the effect of more than one variable on an outcome
into consideration, the calculations are statistically very complex.
How do we measure cancer severity?
When considering whether to change a behavior, we might like to have more information in addition to
just the relative risk of developing the disease associated with it. For example, we might want to know
how severe the disease we are concerned about will be. The severity of a cancer is determined based on
three major characteristics: the number of people who will get it (incidence rate), the number of people
who will die (death rate), and the number of people who, having developed it, will still be alive five years
later (five-year survival rate).
Wo r k b o o k
Lesson 1.5
MC Questions:
4. Which of the following is not useful
to calculate an odds ratio for a risk
factor? (Circle all correct.)
aa. Number of people exposed to a
risk factor.
bb. Number of people who acquired
a disease.
cc. Number of people who died from
that disease.
dd. Number of people who received
a treatment.
5. True or false: A risk factor with an
odds ratio of 7 is very likely to be
responsible for causing cancer.
aa. True.
bb. False.
6. Which of the following is useful to
determine the severity of a type of
cancer?
aa. Incidence rate.
bb. Death rate.
cc. Five-year survival.
dd. All of the above.
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LESSON READINGS
Let’s look at the statistics for eight of the most common cancers arranged by incidence rate:
Tumor Type
DEFINITIONS OF TERMS
Incidence rate – the number of
people who develop the disease
per 100,000 people in the
population.
Death rate – the number of
people that die from the disease
per 100,000 people in the
population.
Incidence Rate Death Rate
(# w/ disease per 100K people) (# that die per 100K people)
Five-year
Survival Rate
All Types
465.2
178.7
65.2%
Prostate
69.4
9.1
98.9%
Breast
67.2
12.9
89.2%
Lung
62.6
50.6
15.7%
Colorectal
46.3
16.7
63.8%
Leukemia
12.5
7.1
53.2%
Pancreas
12.1
80.0
6.0%
Stomach
7.6
3.6
25.6%
Liver
7.5
5.5
16.6%
Both the incidence rate and the death rate are reported as the number of people per 100,000 (100K)
people in the population. So we can see that while prostate cancer is the most frequent cancer in the
population most people survive it. Prostate cancer is very slow growing and clinical symptoms usually
appear in the elderly. The five-year survival rate is also the highest for any of the cancers reported. All of
these considerations raise questions as to whether it is appropriate to treat prostate cancer aggressively,
especially if the treatment itself is very debilitating. We shall come back to this later.
Contrast prostate cancer with lung cancer. Lung cancer is less prevalent, but it has the highest death
rate and the number of people with lung cancer still alive after 5 years is low. This tells us that it would be
well worth changing any behavior that increases the risk of developing lung cancer (such as working with
asbestos, or smoking). Pancreatic cancer also has a poor prognosis. At least 80% of people with it will
die and fewer than 10% are alive after 5 years, indicating that good treatment is still lacking. Exposure to
carcinogens, like cigarette smoke, is also a significant risk factor for pancreatic cancer.
Wo r k b o o k
Lesson 1.5
The best way to assess disease severity is five-year survival, the final statistic on the table. While death
rates and incidence rates describe the extent that a cancer is present within a population, the five-year
survival rate provides an idea of how well the cancer can be managed, which is the ultimate goal. The
5 year survival with prostate and breast cancer is similar (98.9% vs 89.2%) but whereas many people
survive prostate cancer because it grows slowly, people survive breast cancer because detection and
treatment have improved considerably. Contrast these numbers with those surviving after pancreatic or
liver cancer, which have few effective treatments. In general cancers with five-year survival rates below
40% have poor treatment options. These therefore include lung, pancreas, liver and stomach. Brain
cancer also has poor survival but is not included on this chart.
MC Questions:
7. Based upon the table shown on the
left, which cancers are the most
severe?
aa. Breast and Prostate;
bb. Pancreas and Lung;
cc. Liver and Stomach;
dd. Leukemia and Colorectal.
8. Which of the following statistics
informs you that a cancer is easy to
treat? (Circle all correct.)
aa. Incidence Rate.
bb. Death Rate.
cc. Five-year survival.
dd. Odds Ratio.
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STUDENT RESPONSES
The odds ratio of artificial sweeteners (present in Diet sodas, like Coke and Pepsi) having a direct effect on various cancers
is 0.8. Would you avoid artificial sweeteners to reduce your risk of cancer? Why or why not? Is there another reason why you
might avoid artificial sweeteners, and might this be linked to cancer?
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Remember to identify your
sources
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Lesson 1.5
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TERMS
TERM
For a complete list of defined
terms, see the Glossary.
Wo r k b o o k
Lesson 1.5
DEFINITION
Death Rate
The number of people that die from the disease per 100,000 people in the population.
Estrogen-like compounds
Chemicals commonly found in plastics that behave like the hormone estrogen. A risk factor for cancer.
Five-year survival rate
The percent of people diagnosed with the disease who are still alive after five years.
Hormone
An internal signal in the bloodstream that regulates cell and tissue growth and development.
Incidence rate
The number of people who develop the disease per 100,000 people in the population.
Obesity
A medical condition due to accumulation of excess fat that can reduce life expectancy.
Odds ratio
The odds of a disease appearing in the population after exposure to a risk factor.
Relative risk
The extent to which a risk factor is responsible for causing disease in a population.
Risk factor
Any agent that increases the chance that someone will develop a disease.
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