Colon Cancer and Physical Activity a Content Analysis

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Colon Cancer and Physical Activity: A Content Analysis
of Reciprocal Relationship
Ivo P. Janecka
Health Research International Boston, MA.

Background: Colon cancer is among the leading causes of cancer mortality and its incidence is increasing worldwide. This
is true in spite of broad basic research into colon cancer while, concurrently, physical activity has been shown to offer
significant preventive potential. This background led to the formulation of the following research questions:
• Why is physical activity so effective in decreasing the incidence of colon cancer?
• Is there a common denominator to colon cancer and physical activity, which has a reciprocal function?
• Knowing the potential for public health impact of physical activity on colon cancer, has physical activity-colon cancer
relationship been in the forefront of research efforts?
Methods: Content analysis of archival literature has been carried out on census of 32,822 message units, extracted from
the National Library of Medicine and its PubMed database. The following search terms were used: colon cancer, physical
activity, melatonin, age/genetics, diet (obesity, vitamin D, calcium), immunity/inflammation, and bioactive substances
incorporating insulin-like growth factor 1, interleukins, and prostaglandins. The research timeframe for each category began
with the first article published and ended with the last one printed in 2005.
Results/Conclusions: The effectiveness of physical activity in decreasing the incidence of colon cancer is likely the result
of its biologic activity within not one or two but all of the major known colon cancer etiologies, demonstrating a powerful
reciprocal relationship. Melatonin is identified as a plausible common denominator of colon cancer and physical activity.
The greatest volume of publications deals with colon cancer and genetics. A significant societal health care impact could
be achieved by adopting physical activity as a major cancer control strategy.
Keywords: colon cancer, physical activity, melatonin, exercise, content analysis


The incidence of colon cancer is increasing worldwide. Ten million people developed colon cancer in
2000 and about five million died from this cancer. Many risk factors are known and include: diet, inadequate physical activity, obesity, alcohol consumption, and smoking, as well as family history and aging.
The most prominent among the etiologic factors are physical inactivity and obesity, which are strongly
and consistently associated with higher risk of colon cancer (Willer, 2003). Emmons et al. (2005) state
that colorectal cancer (CRC) is the fourth leading cause of cancer and the second leading cause of
cancer death in the United States.
A strong preventing influence of physical activity on colon cancer development has been well
documented in the literature. The mechanisms of action, however, have been mostly hypothesized
(Slattery et al. 1997; McTiernan et al. 1998; Thune and Furgber, 2001; Peters et al. 2001).
This study attempted to shed additional light on “how and why” a single preventive step, physical
activity, can be so highly effective in lowering colon cancer incidence. A search has also been made to
identify a plausible common denominator for colon cancer and physical activity that expresses reciprocal

Material and Methods

An archival literature research, through content analysis methodology, was chosen as the framework
for this study. The three-dimensionality of this study had the following parameters: the breadth
Correspondence: Ivo P. Janecka, M.D., M.B.A., Ph.D., 333 Westbrook Rd., St. Helena Island, SC 22920.
Email: [email protected]
Copyright in this article, its metadata, and any supplementary data is held by its author or authors. It is published under the
Creative Commons Attribution By licence. For further information go to:

Clinical Medicine: Oncology 2007:1 81–89



encompassed all articles published on topics
extracted with specific key search terms of colon
cancer, physical activity, melatonin, and related
terms of age/genetics, diet (obesity, vitamin D,
calcium), transit time plus immunity/inflammation,
and bioactive substances incorporating insulin-like
growth factor 1, interleukins, and prostaglandins.
The depth of this methodology included a detailed
examination of all relevant articles and a numerical
summary of all message units, which included the
key search terms and their combination. The methodological timeframe began with the first article
published on a given topic and ended with the last
one printed in 2005.
Data was collected through an electronic search
of the National Library of Medicine’s database,
PubMed. Neudorf’s outline of content analysis
methodology was used allowing systematic, objective, and quantitative analysis of message units
(Neuendorf, 2002).
A unit of data analysis in this study was represented by a single published article as generated
by the PubMed database in response to the key
word input.


Physical activity was documented to exert its beneficial influence in all previously identified main
colon cancer etiologic categories. Physical activity
and colon cancer have a strong but reciprocal
mutual relationship. With decreasing physical
activity there is increasing incidence of colon
cancer and vice versa.
Melatonin was identified as a plausible common
denominator to colon cancer and physical activity
due to the fact that it takes an active but reciprocal
part in all colon cancer etiologic categories. It is
diminished during cancer development but its level
rises with moderate and strenuous physical
The numbers of publications identified are summarized in Figure 1. It illustrates that 10,047
articles were published on the topic of colon cancer and genetics but only 249 dealing with colon
cancer and physical activity. Similarly, only 243
articles were published addressing colon cancer
and obesity. The second highest volume of publications dealt with colon cancer and immunity.
Figure 2 highlights the fact that physical activity
takes part in all colon cancer etiologic categories.
Under positive influence of physical activity, these

categories become health benefit groups. The
highest number of publications-4,288- dealt with
physical activity and obesity. Figure 3 combined
data for colon cancer and physical activity. It provides visual comparison of “what was studied” and
to what extent. The gap between the 10,000 plus
articles on colon cancer and genetics, and the only
200 plus publications related to physical activity
and colon cancer is clearly evident. Colon cancer
and obesity tracks only 200 plus publications.


It has been quite revealing to look at the issue of
colon cancer and physical activity through the
method of content analysis. This process allowed
for numerical and graphic comparisons of the
research efforts of the scientific community studying the major colon cancer etiologic categories and
the impact of physical activity within identical
groups (Fig. 3). The major emphasis of researchers,
as expressed by the highest number of publications,
was found to be centered on the topic of genetics
and colon cancer. Comparing the absolute numbers
of publications-10,047 for genetics and colon cancer, and 249 for physical activity and colon cancer,
the research effort into physical activity represents
only about 2.5% of that expended on the field of
genetics. Epidemiological data, however, suggest
that the ration should probably be reversed in order
to achieve the greatest societal health impact. This
concept is based on reports that genetics play only
a relatively small role in the etiology of colon
cancers while it is estimated that physical activity
could prevent 40–70% of colon cancers (Shephard
and Shek, 1995; National Institute of Health, 2005;
Fleet, 2006). If one considers a number of publications as a proxy to the effort and funding of the
research community, a large discrepancy is apparent between the research into the genetics of colon
cancer and the influence of physical activity.
A similar gap exists on the topic obesity-only
200 plus articles were found, while obesity is
quoted to be one of the key causative factors of
colon cancer (Willer, 2003). Slattery et al. (2005,
p 148) also indicated that it is obesity, physical
activity and energy intake that appeared to alter
the risk of colorectal cancer while this risk
appeared to be minimally influenced by genetic
Batty and Thune (2000, p 1424) elaborated that
physical activity has a marked effect on several
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Colon cancer-physical activity

Colon cancer etiologies







Figure 1. Number of publications for search term combinations of colon cancer and etiologic categories including the first publication year.

functions of the human body that may influence
cancer risk and that this association may vary
across the life course. These effects, according to
the authors, vary according to the mode, duration,
frequency, and intensity of the activity which produce changes in bowel motility, endogenous
hormones, energy balance, immune function and
DNA repair. Also, Slattery and Potter (2002, p 913)
wrote, that physical activity has been consistently
but inversely associated with colon cancer
In real time, however, the individual etiologic
factors do not work in isolation. Multifactorial
influence seems to be the norm. For example,
Fernandez et al. (2004) compared the effect of
environmental factors and family history on the
risk of developing colon cancer. For subjects
Clinical Medicine: Oncology 2007:1

without family history, they found that the odds
ratio for colon cancer was 2.27; it reached 3.20 for
those with family history and low risk factor score;
and finally, for those with family history and high
risk factor score, the odds ratio was 7.08.
Examining the individual etiologic categories
also revealed some interesting observations. As
Emmons et al. (2005) documented, there is a
parallel aging-colon cancer relationship. This
observation heralds that colon cancer incidence
will continue to increase with its accompanying
human and economic cost. This is due to the fact
that, as The National Institute of Health (2005, p
1) reported, there is an evolving striking shifts in
aging on a population scale. One pathway of influence, between aging and colon cancer, may be, as
Shephard and Shek (1995, p 1) reported, the


Physical activity benefits

Figure 2. Number of publications for search term combinations of physical activity and its health benefits categories including the first
publication year.

depression of immune function that is secondary
to old age which is known to be associated with
an enhanced susceptibility to tumors. These authors
also demonstrated exercise-induced changes in the
activity of macrophages, natural killer cells, lymphokine activated killer cells, neutrophils, and
regulating cytokines suggesting that immunomodulation may contribute to the protective value
of exercise. Along the same line, Johe and Osterud
(2005, p 324) confirmed that physical exercise is
associated with cellular activation of the blood
Another negative societal shift that is evolving
and predisposing a great number of people to colon

cancer, according to Abu-Abid, Szold and Klausner
(2004, p 73), is the fact that more than half of adult
Americans are overweight or obese. Furthermore,
it is of great concern that older children and adolescents in the United States currently do not
achieve the recommended intake of calcium, as
reported by Greer and Krebs (2006, p 578). Regular physical activity, on the other hand, provides
health benefits, including the reduction in risk
of colon cancer, and premature mortality, as
documented by Belza and Warms (2004, p 181).
Slattery et al. (2005, p 75) considered the degree
of energy expenditure as an important factor in the
etiology of colon cancer.
Clinical Medicine: Oncology 2007:1

Colon cancer-physical activity

Figure 3. Number of publications for search term combinations of colon cancer (CA) and etiologic categories, and physical activity (PA) and
its health benefits categories including the first publication year.
Note: Negligible numbers of articles for search terms CA-Transit time (85), PA-Transit time (68), CA-Hyperinsulinemia (52).

Vitamin D, as observed by Slattery et al (2004)
who identified cellular vitamin D receptors, is
involved in cell growth and differentiation. Freedman, Dosemeci, and McGlynn (2002, p 257)
previously commented on the correlation between
the exposure to sunlight and the mortality from
female breast, ovarian, prostate, and colon cancer.
Closely related to the issue of vitamin D and colon
cancer is the impact of calcium. Fleet (2006, p 527),
for example, indicates that colon cancer risk is
reduced both by high dietary calcium consumption
and high total dairy food intakes. He observed that
dietary calcium and vitamin D status were comodulators of colon cancer and that vitamin D
Clinical Medicine: Oncology 2007:1

deficiency abolished the protective effects of
calcium on tumor formation. Cosman (2005, p 73)
argued that because bone loss with age is universal,
its prevention requires adequate vitamin D intake
and regular physical activity.
Inflammation is another suspected pathway
leading to colon cancer. This is derived from observations similar to Clevers (2006, p 761) who points
out, for example, that chronic inflammation of the
intestine and colorectal cancer are closely associated and that the risk of colorectal cancer among
patients with ulcerative colitis is an order of magnitude higher than the risk among those without it.
Pertinent to the question of the role of inflammation


in colon cancer etiology are also the observations
on the effect of nonsteroidal anti-inflammatory
drugs (NSAIDs) and the incidence of colon cancer.
Potter (1999, p 916) summarized that NSAIDs,
including aspirin, have been consistently associated with a reduced risk of colorectal cancer in
rodents and that aspirin and celecoxib, a specific
cyclooxygenase-2 [COX-2] inhibitor, restrained
carcinogenesis. All the mechanisms by which
physical activity may affect colon cancer are not
clear, however. For example, Hou et al. (2004, p
860) considered interleukin 1 levels as playing an
important role in the etiology of colon cancer, and
Slattery et al. (2003, p 214) proposed that biologic
mechanisms through which physical activity
reduces the risk of colon cancer may involve altering prostaglandins levels. In addition, DeLellis
et al. (2004, p 1444) confirmed that a high circulating concentration of insulin-like growth factor-1
(IGF-1) and the low circulating concentration of
IGF binding protein-3 (IGFBP-3) have been associated with increased risk for several cancers
including colorectal cancers. They also found a
positive correlation between IGF-1 levels and
colon cancer incidence rates within a multiethnic
cohort for both sexes. Subsequently, it was Slattery
et al. (2005, p 148) who noted that high serum
IGF-1 levels are associated with an increased risk
of colorectal cancer. Willer (2003, p 283) stated
that increased physical activity and weight reduction increases IGF-1 binding protein production
and therefore decrease IGF serum level thus diminishing the availability of free sex hormones, an
effect that should further decrease the cancer risk.
Hou et al. (2004, p 860) observed that physical
activity is a strong determinant of insulin resistance
and hyperinsulinemia, and that physical activity
appears to modify insulin sensitivity.
Of note are also observations by Batty and Thune
(2000, p 1424) regarding the fact that physical activity reduces the risk of colon cancer possibly even
through the increase in bowel transit time and thereby
the duration of contact between fecal carcinogens
and colonic mucosa. Hou et al. (2004, p 860) has
made similar observations. The increase of transit
time, referred to by the authors, likely accompanies
only moderate physical activity as intensive activity
would diminish the intestinal transit.
Reiter and Robinson (1995, p 7; p 20; p 185)
describe melatonin as a substance that plays a
primary role in the body’s defense against cancer
and hence this substance was investigated for its

possible relationship to colon cancer and physical
activity. The connection of melatonin to the colon
cancer etiologic categories and physical activity is
highlighted with the following examples: Among
its many functions, melatonin protects and
enhances the immune system. As previously stated,
there is a gradual crippling of the immune system
that comes with age which parallels the known
age-related decline of melatonin. Reiter and
Robinson (1995) also state that calcium is vital for
melatonin production thus connecting the vitamin
D, calcium, melatonin and colon cancer. Das (2005,
p 343) pointed out that calorie restriction which
diminishes obesity also enhances melatonin production. Vijayalaxmi et al. (2002, p 2575) stated
that the gut seems to produce proportionately more
melatonin than does the pineal gland. In addition,
they confirmed that melatonin markedly reduces
acute inflammation and that it stimulates the production of interleukins. Knight and Thompson
(2005, p 1114) confirm that exercise was found to
be significantly related to an increase in melatonin
production. This study was preceded by Poon et al.
(1996, p 77) observation that melatonin binding
sites were identified in the mucosa of the human
colon. The brain center of circadian rhythm which
is related to melatonin production is entrained by
incoming light into the eyes; it is the lack of light
during night time that allows for the production of
beneficial melatonin. The undesirable resetting of
the day/night rhythm can be generated by prostaglandin E2 (Tsuchiya et al. 2005). Physical activity lowers the levels of prostaglandin E2.
Considering the above information, it seems reasonable to regard melatonin as a likely common
denominator to colon cancer and physical activity.
In the colon cancer etiologic categories, it is diminished, but with physical activity, its level is
enhanced converting the etiologic categories into
beneficial health impact groups.
The scientific literature continues to accumulate
evidence that physical activity lessens the chances
for colon cancer development. Zhang et al. (2006)
found that twice per week engagement in recreational activity reduced colon cancer incidence by
30% for all sites, and 40% for the right colon.
Those participants who had both high occupational
and recreational physical activity experienced the
lowest cancer risk (odds ratio of 0.5).
Much remains to be done to fully understand the
reciprocal relationship of colon cancer and physical
activity. Most recent articles, published by Campbell
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Colon cancer-physical activity

and McTiernan (Cambpell, McTiernan, 2007), made
additional observations in this regard. They found
decreases in serum estrogen, testosterone, and
insulin in overweight, sedentary postmenopausal
women with a 1 year exercise program (aerobic
exercise, 45 min/d, 5 days/week). Furthermore,
Campbell and co-investigators (Campbell et al.
2007) explored the expression of pro- and antiapoptotic proteins in colon crypts. They found that
the density of Bax, which is an apoptotic promoter,
increases in the crypts following a 13-month program in male exercisers.


Colon cancer and physical activity operate through
the same categories of influence, labeled either etiologic or health benefit categories, but with an opposite effect. Physical inactivity promotes metabolic
abnormalities in each of the colon cancer etiologic
categories, thus increasing the risk of colon cancer
development. On the other hand, enhanced physical
activity normalizes metabolic processes within all
such categories, thus contributing to better health
and lower cancer incidence. No other currently
known colon cancer preventive step, besides physical activity, is involved in a reciprocal fashion with
all the potential colon cancer etiologic categories.
Societal health might benefit greatly if research effort
into colon cancer was proportionate to the epidemiological evidence of its health impact.
This study also identified melatonin as a common denominator to colon cancer and physical
activity exhibiting a beneficial and reciprocal


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