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Epidemiology and prevention of

colorectal cancer
ICD9: 153, 154

1. Significance

The second leading cause of cancer death in men & women (The
# 1 is..). It accounts for 10% of all cancer deaths in the
USA.

More lives are lost each year to colorectal cancer than to


breast cancer and AIDS combined.

it accounts for nearly half of the diagnosed new cases of


cancer.

The incidence and mortality of colorectal cancer (CRC) show


increasing tendency worldwide.

Compared to 2000 data, the new cases in 2007 approximate


1,200,000 and the death cases 630,000, a total increase of
27% and 28% and an annual increase of 3.9% and 4.0%,
respectively.

The overall 5-year survival rate for CRC is 61%; 91% for CRC
in local stage.

2.

Pathophysiology

Not well understood


Some research suggests delay transit of fecal material.
Related to:

Low fiber diet intake


Lack of physical activity

Predominant cell type is adenocarcinoma (96% of all cases).

3.

a.

Descriptive epidemiology
High-Risk Groups
Gender: 44% Higher for men
Race: 15% higher for Blacks than for Whites.
Age: Incidence rises sharply after the age of 50 years;
>80% of diagnosed cases of colorectal cancer occur
in patients older than 55 years.
The mean age at diagnosis is 62 years.
SES: People in higher socioeconomic groups.
Certain genetic and medical conditions Predispose to CRC include:

First kin relatives


Familial polyposis
Inflamatory bowel disease (e.g. Ulcerative colotis, Crohns ).

b.

Geographic distribution

Worldwide,
CRC is highest in developed countries in North
America, Northern and Western Europe, and New
Zealand.

Extremely low in Japan; Japanese immigrants to the


USA have similar rates as the Americans.

In USA, CRC is highest in Northeast and North-Central


states, lowest in Western and Southwestern states.

c.

Time trends
The incidence of CRC varies regionally and changes over the

time.
a.

b.

In previously identified high-incidence areas, there are


three tendencies:

The incidence keeps rising such as in UK,

The incidence is stable such as in New Zealand, and

The incidence tends to decrease such as in US and


Western Europe.
In previously identified low-incidence areas, the incidence
of CRC is increasing, such as in Japan, Hong Kong,
Singapore, Hungary, Poland, and Puerto-Rico, especially in
Japan, where the incidence increases the fastest.

Since 1991, the average increase in mortality of CRC is 4.7%


every year.
The increasing number of female patients and the shift of the
tumor location to the right side are also the trends noticed for
CRC in recent years.

4. Risk Factors
a.

Magnitude of risk factors


Modifiable risk factors for colorectal cancer, US

Magnitude
Strong RR>4
Moderate RR 2-4
Weak RR <2

Risk Factor
None
None
High fat-diet
Low-vegetable diet
Physical inactivity

Pop.Att.Risk (%)
15-25
25-35
32

Possible

Alcohol
Occupation (asbestos, wood dust, metals)
Aspirin use (protective)
Obesity
Vitamin D deficiency
smoking

Relative Risk= Risk of disease/death in the exposed population


Risk of disease/death in the unexposed population
Population Attributable Risk is: Proportion of a disease in a
population that is associated (attributed to) a certain risk factor.

b. Population Attributable Risk


Up to one-half of CRC may be related to diet.
Within this proportion, it is estimated that 15%-25% of CRC may be
related to fat intake and that 25%-35% may be related to low
intake of fruits and vegetables
An estimated 32% of CRC may be related to physical inactivity.

5.
a.

Prevention and Control Measures


Prevention
The overwhelming evidence indicates that primary prevention of colon
cancer is feasible.
At least 70% of colon cancers may be preventable by moderate
changes in diet and lifestyle.
i. Diet and Nutrition

There is convincing evidence from epidemiological and experimental


studies that dietary intake is an important etiological factor in
colorectal neoplasia.
The precise mechanisms have not been clarified, yet several lifestyle
factors have a major impact on colorectal cancer development.

- Fats and meats


US Nurses Health Study:
In 1990 Willett et al published the results from follow up of
88,751 women aged 34-59 years who were without cancer or
inflammatory bowel disease at recruitment.

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Consumption of animal fat was found to be associated with


increased risk of colon cancer, after adjustment for total energy
intake.

RR in the highest compared with the lowest quintile = 1.89 (95%


confidence interval 1.13 to 3.15) (P=0.01).
No association was found with vegetable fat.
RR in women who ate beef, pork, or lamb as a main dish every day
was 2.49 (1.24 to 5.03) compared with women reporting
consumption less than once a month.
The study data supported:
- the hypothesis that a high intake of animal fat increases the
risk of colon cancer, and
- the existing recommendations to substitute fish and chicken for
meats high in fat.

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- Fiber
Fiber has many components commonly grouped into:
insoluble, non-degradable constituents (mainly found in cereal fiber)
and soluble, degradable constituents, such as pectin and plant gums
(mainly found in fruits and vegetables).

Epidemiological studies have reported differences in the effect of


these components.
Many studies, however, found no protective effect of fiber in
cereals but have consistently found a protective effect of fiber in
vegetables and perhaps fruits.
This might reflect an association with other components of fruits
and vegetables, with fiber intake acting merely as an indicator of
consumption.
Recent epidemiologic studies tended not to support a strong
influence of fiber; instead, some micronutrients or phytochemicals
in fiber-rich foods may be important. Folate (and methionine) is
one such nutrient that has received attention lately and is being
studied in randomized intervention trials.

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International and migrant population data indicate that a


substantial reduction in the incidence of CRC could be achieved in
10 years through dietary changes alone:

By increasing per capita consumption of fiber from fruits and


vegetables to 20-30 grams/day.

By decreasing per capita consumption of fat to below 30% of


total calories.
ii.

iii.

Vitamin D
A scientific review of literature found that vitamin D was beneficial
in preventing colorectal cancer. There is an inverse relationship
with blood levels of 80 nmol/L or higher. These levels are
associated with a 72% risk reduction compared with lower than 50
nmol/L levels.
Chemopreventive agents (aspirin and postmenopausal estrogens):
There is much evidence suggesting an inverse relationship between
aspirin or non-steroidal anti-inflammatory drug (NSAID)
consumption and CRC incidence and mortality.

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However, NSAID consumption is not problem-free; 1997 data


show 107,000 hospitalisations and 16,500 deaths due to NSAID
consumption in the U.S. alone.
Therefore, drugs that have more acceptable side-effect profiles
are required.
Cyclo-oxygenase (COX)-2-specific inhibitors, which have an
improved safety profile, seem to be well-suited drug candidates
for CRC prevention.
Pharmacology and genetics are collaborating to develop new
chemoprevention agents designed to affect molecular targets
linked to specific premalignant or predisposing conditions.

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iv.
v.

Physical inactivity, and to a lesser extent excess body weight,


are consistent risk factors for colon cancer.
Exposure to tobacco products early in life is associated with a
higher risk of developing colorectal neoplasia.

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Screening for CRC

The evidence is convincing that there are substantial benefits to


screening in asymptomatic adults.
U.S. Preventive Services Task Force (USPSTF) recommends
screening for colorectal cancer in all asymptomatic adults from 50
to 75 years of age.
Balancing the small benefit and potential increased harms, the
USPSTF does not recommend routine screening in asymptomatic
adults from 75 to 85 years of age and
recommends against screening in asymptomatic adults older than 85
years of age who have previously been adequately screened.

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screening for colorectal cancer with:

High-sensitivity fecal occult blood testing (fecal DNA and fecal


immunochemical testing)
sigmoidoscopy, or
colonoscopy
Modeling evidence suggests that population screening programs
between the ages of 50 and 75 years using any of the following 3
regimens will be approximately equally effective in life-years
gained, assuming 100% adherence to the same regimen for that
period.

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annual high-sensitivity fecal occult blood testing,


This strategy, (sensitivity for cancer 70%) that has a false-positive
rate less than 10% (that is, specificity >90%), is estimated to
require the fewest colonoscopies while achieving a gain in life-years
similar to that seen with screening colonoscopy every 10 years
2)
sigmoidoscopy every 5 years combined with high-sensitivity fecal
occult blood testing every 3 years, and
3)
screening colonoscopy at intervals of 10 years.
1)

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