1. Obesity and Cancer
Short Analytical Essay
Department of
Physiology
P.R.Jayawickrama
MD/2011/4114
34th
batch
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2. Obesity
Obesity is a disorder of body weight regulatory systems characterized by an accumulation of
excess body fat (1). In early ages in human civilizations, in which day today life required a
high level of physical activity and food was only available intermittently, a genetic tendency
favoring storage of excess calories as fat had a survival value. But, in modern era the
abundance of food has encouraged people to eat much. This,with the combination of less
activity levels found in developed countries,caused in a tendency for the sustained deposition
of fat.The prevalence of obesity increases with age. As the obesity in the world has increased
so the risk of developing associated diseases, such as diabetes mellitus, hypertension, and
cardiovascular disease and also it increase the risk of cancer.
Markers of the Obesity (1)
*Body mass index
* Body fat percentage
With the development of medicine they invented a standard scale for measuring obesity.so in
these days BODDY MASS INDEX (BMI) uses as the surrogate marker for body fat content,
it is calculated as:
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3. B M I = ( weight in kg ) / ( height in meters ) 2
or
B M I = ( weight in lb ) / ( height in inches ) 2
× 703
In use, The healthy range for the BMI is between 19.5 and 25.0.
BMI between 25 and 29.9 kg/m2 is called overweight, and a BMI higher than 30 kg/m2 is
called obese(2). But BMI is not a direct estimate of adiposity and doesn’t take consider the
fact that some individuals have a high BMI due to a high amount of muscle mass. Because of
this, the much better way to define obesity is to actually measure the percentage of total body
fat. Obesity is usually defined as 25 per cent or greater total body fat in men and 35 per cent
or greater in women.
METHODS OF ESTIMAING THE BODY FAT PERCENTAGE
*measuring skin-fold thickness,
*bioelectrical impedance,
*underwater weighing,
but above methods are very rarely used in general practice,and also there are debates on
methods like measuring skin fold thickness(3) ,so BMI is commonly used to assess obesity in
clinics..
CAUSSES FOR OBESITY
1. Greater Energy Intake than Energy Expenditure.
The main cause for obesity is Greater Energy Intake than Energy Expenditure(4).When
greater quantities of energy (in the form of food and drinks) enter the body than the amount
that expended, the body weight rises,so most of the excess energy is stored as fat in the
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4. adipose tissues,mainly in the form of triacylglecerols(5).so,excessive adiposity (obesity) is
caused by energy intake in excess of energy output. For each 9.3 Cals of excess energy that
uptake to the body, approximately 1g of fat is stored in adipose tissues.Fat is stored mainly in
adipocytes in subcutaneous tissue and in the intraperitoneal cavity in the abdomen, although
the liver and other tissues of the body also store high amounts of lipids in obese individuals.
also the amount of adipocytes are also rises with the weight gain.as a example an extremely
obese person may have as many as four times as many adipocytes, each containing twice as
much lipid, as a lean person.when a person has become obese and a stable weight is
gained,the energy uptake again equals to the energy output.so if a person need to lose
weight,he or she should maintain energy intake lesser than the energy expenditure.
2. Decreased Physical Activity and Abnormal Feeding Regulation as Causes of Obesity.
Though genes play a vital role in determining food uptake and energy utilization,lifestyle and
environmental issues also play the major role in many obese people.The rapid rise in the
prevalence of obesity in the past few decades show the important role of lifestyle and
environmental issuses.Because genetic changes couldnt have occurred so fast.
3. Sedentary Lifestyle Is a Major Cause of Obesity.
Regular physical training and physical exercises are known to increase muscle mass and
reduce body fat mass,so inadequate physical activity is generally associated with reduce
muscle mass and increased lipid content of the body.
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5. 4. Psychological Factors which are Contribute to Abnormal Feeding.
For example, people often gain large amounts of weight during or after stressful
situations,such as the death of a parent, a severe illness or even mental depression.
5. Childhood Over nutrition.
6. Neurogenic Abnormalities as a Cause of Obesity.
Individuals with hypophysial tumors that encroach on the hypothalamus often develop
progressive obesity.
7. Genetic Factors as a Cause of Obesity(6).
We can often identify obese people within the same family background.though it has been
difficult to determine the exact role of genetics in contributing to obesity,scientists suggest
that 20% to 25% of cases of obesity may be caused by genetic factors.
Genes can contribute to obesity by causing abnormalities of:
* One or more of the pathways that regulate the feeding centers.
* Energy expenditure and fat storage. There are three monogenic (single-gene) causes of
obesity.they are:
* Mutations of MCR-4 -the most common monogenic form of obesity discovered thus far.
* Congenital leptin deficiency caused by mutations of the leptin gene-which are very rare
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6. * Mutations of the leptin receptor-also very rare.
but these monogenic forms of obesity account for only a few percentage of obesity. It is
understandable that the many gene variations interact with environmental factors to influence
the total amount and distribution of body fat.
As discribed in the above obesity become a major health issue in the world, and it causes and
enhance the ill effects of many disease conditions like
*diabetes mellitus(DM)(7).
*high blood pressure and other cardiovascular diseases,
*strokes.
* cancers.
in the following segment im going to illustrate what are the co-relations between obesity and
cancers.
The relationship between obesity and cancer
According to modern researches obesity is associated with high risks of many cancer types,
like:
1 ) breast cancers(mainly post menopause).
2 ) cancers in the oesophagus.
3 ) cancers in the pancreas.
4 ) cancers in the colon and the rectum.
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7. 5 ) cancers in the endometrium.
6 ) cancers in the kidney.
7 ) cancers in the tyhyroid.
8 ) cancers in the gallbladder.
to understand the co-relation between the cancer and obesity,there is a set of possible
mechanisms have been suggested by the scientists,they are;
1 ) Adipose tissue manufactures high amounts of estrogen, high levels of which have been
co-related with the risk of breast(8),endometrial, and some other cancers.
2 ) Fatty people usually have high levels of insulin and insulin-like growth factor-1 (IGF-1)
in their plasma(this condition known as insulin resistance),this condition may help the
development of certain tumors(9).
3 ) Adipocytes manufacture hormones,known as adipokines,these hormones may stimulate or
inhibit cell growth and function.as a example, leptin, which can find in higher amounts in
fatty people, seems to promote cell proliferation.
4 ) Adipocytes can have direct and indirect effects on other tumor growth regulators,
including mammalian target of rapamycin (mTOR) and AMP-activated protein kinase.
5 ) Fatty individuals usually have chronic low-level, or “sub acute,” inflammation, which
may associated with higher risk of cancer.
Also there are other possible mechanisms like,
1 ) altered immune responses.
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8. 2 ) effects on the nuclear factor kappa beta system.
3 ) oxidative stress.
in the following section I will discuss how the above pathophysiological mechanisms give
rise to cancers.
Dysfunctional Adipose Tissue
Though the main function of the adipose tissue is to store lipids but also they are highly
functioning endocrine and metabolic tissues.these tissues are consists of many cell types,
such as adipocytes, pre-adipocytes, macrophages,fibroblasts,and also blood vessels.these
different cells product number of adipokines, such as leptin, adiponectin, vascular
endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α), interleukin (IL)
-6. ,and plasminogen activator inhibitor (PAI)-1. As adipose tissue grow,the adipocytes grow
bigger and these adipose tissues start to manufacture above factors in high amounts.
These obesity- corelted changes of adipose tissue metbolism are play a main role in the
development of insulin resistance & the production of leptin which is a major co-relation
between obesity and cancer,except that these factors also cause type 2 diabetes, and obesity-
related cardiovascular diseases.
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9. Insulin Resistance
Insulin resistance and the insulin-like growth factor (IGF) -1 system may explain in part the
link between obesity and cancer. In insulin resistance, which is commonly associated with
obesity,plasma insulin levels increase.Insulin enhance the effect of growth hormone (GH)
receptors in the liver,and this causes a stimulation in production of IGF-1.
Both insulin and insulin-like growth factor (IGF) -1 are play a vital role in cancer
development through binding with the insulin receptor (IR) and IGF-1 receptor (IGF-1R).
Insulin-like growth factor-1 can inhibit apoptosis and aid cell growth and development
through several mechanisms(9).
Also this unbalanced tissue environment aids the stepwise accumulation of genetic mutations
and it helps the carcinogenesis.
modern studies have shown that individuals with high levels of insulin-like growth factor-1
have an high risk of several cancer types,including postmenopausal breast cancer,prostate
cancer,colorectal cancers. high levels of serum insulin is also a risk factor for breast cancer in
women and also increases the risk of colorectal cancer and endometrial cancer.Further more,
diabetes mellitus (D.M.), which is characterized by insulin resistance,is also associated with
high risk of breast,pancreatic,colorectal cancers(9).So the Insulin resistance is play a
prominent role in carcinogenesis(9) , and it is one of the major mechanisms shows the co-
relation between obesity and cancer(9).
Adipokines
Adipose tissue cells manufactures a variety of biochemical substances which act like
hormones and cytokines,which are known as adipokines.Adipose tissue dysfunction as a
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10. result of obesity unbalanced the serum levels of adipokines,this may cause to obesity-related
carcinogenesis.
Leptin
Leptin is a protein hormone,it is secreted by adipocytes in the adipose tissuses, and plays a
major role in regulating the energy balance,by regulating the metabolic rate.Levels of leptin
are higher in obese individuals,. Though the findings of sciencetific studies of the relationship
between systemic leptin levels and breast or prostate cancer are inconsistent, but an
association reported for colorectal cancer and for the endometrial cancer.Also many cancers
such as colorectal, breast, and endometrial cancers overexpress the leptin receptor
ObR.studies have shown that leptin has mitogenic actions in the cancer cell lines,it vary one
from other by the type of cancer.it stimulates the growt and development of the breast,the
oesophagus, and the prostate cancer,But inhibits the growth of the malignent cells in
pancreatic tissue.
Though Mitogenic and anti-apoptotic functions of leptin described in both colon and prostate
mlignent cells,represion of MAPK and PI3-K inhibited these effects,this shows that these
pathways underlie the growth-encouraging effects of leptin.
In the above section we discussed how the obesity related pathophysiological mechanisms
give rise to cancers in a general aspect.in the following section I consider how the obesity
cause for cancers in specific sites in the body.
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11. Co-relation between obesity and breast cancer.
Modern studies have shown that overweight and obesity are associated with a moderate
increase in risk of postmenopausal breast cancer in women. and mainly in women who have
never used menopausal hormone therapy(MHT) and for tumors that express both
progesterone and estrogen receptors.
The correlation between obesity and breast cancer may be affected by the age of her life in
which she gain weight and becomes obese.Weight gain during adult life, most frequently
from about age eighteen to between the ages of fifty and sixty, has been consistently
associated with higher risk of breast cancer after menopause.
The higher risk of postmenopausal breast cancer is thought to be due to higher levels of
estrogen in obese individuals.After the menopause,the ovaries stop producing hormones,and
then the adipose tissue becomes the most important source of estrogen.As a result of obese
women have more adipose tissue,their estrogen levels are higher,and probably leading to
faster growth of estrogen-responsive breast tumors(8).
According to the sciencetific studies the correlation between obesity and breast cancer risk
may also vary by ethnicity and race. There is rare evidence that the risk associated with
overweight and obesity may be less among African American and Hispanic women than
among white women.
Co-relation between obesity and colorectal cancers.
In men,who have higher BMI is closely associated with elevated risk of colorectal cancer.The
distribution of body fat appears to be an important factor in here,as a example people with
abdominal obesity,show the strongest co-relation with colon cancer risk.
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12. A co-relation between BMI and abdominal obesity with colon cancer risk is also identified in
women, but it is weaker than in men.May be the use of menopausal hormone therapy (MHT)
modify the association in postmenopausal women.
Many mechanisms have been proposed to account for the co-relation between obesity with
increased colon cancer risk.One such mechanism is that elevated levels of insulin or insulin-
related growth factors in fatty individuals may uphold colon cancer development.also the free
adipokines , free fatty acids and many other proinflammatory chemokines which released
from the adipose tissue are known as factors which act a major role in regulating
carcinogenesis(10).
Though obesity is also related with rectal cancer risk,the increase in risk is lesser than the
colon cancer risk.
Co-relation between obesity and endometrial cancers.
Overweight and obesity is clearly related with endometrial cancers,which is cancer of the
lining of the uterus in females.Obese and overweight females have 2 to 4 times greater risk of
developing this disease than female with a normal BMI.
Many reacherchs have also show that the risk of endometrial cancer is higher with elevated
weight gain in adultlife because some studies shows that there is a higher risk of having a
endometrial cancer when a patient develop insulin resistance(11) specially in obese
individuals ,and among women who do not use menopausal hormone therapy(MHT).
Although it hasn’t yet been determined 100% how the obesity is a risk factor for endometrial
cancer,some other studies shows the possibility in combination with low levels of physical
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13. activity and elevated levels of estrogen manufactured by adipose tissue is co related with
endometrial cancer.
Co-relation between obesity and kidney cancers.
Obesity and having high BMI has been markedly related with renal tissue cell
cancer,according to the national cancer institute of USA it is the most commonly found
species of kidney cancer, in both males and females.The way that the obesity related to the
renal cell cancers is not cleared.But the high blood pressure is regarded as a risk factor for
renal cell cancer,but according to the modern studies the co-relation between obesity and
overweight with kidney cancer is not dependent on blood pressure status.May be the high
levels of insulin,which found in obese people play a important role in the development of
the renal cancers.
Co-relation between obesity and oesophageal cancers.
people with higher BMI are about two times as likely as people who have normal BMI to
suffer from a oesophageal cancer type known as oesophageal adenocarcinoma.But many
studies have observed no elevated risk, or even a decrease in risk, with high BMI for the
other major type of oesophageal cancer,which is known as squamous cell cancer.
The mechanisms by which high BMI may develop the risk of oesophageal adenocarcinoma
are not well defined, but according to some studies there are links between IGF-1, high levels
of estrogen (12) with oesophagieal cancers(13).
Also people who are with high BMI are more likely than people with normal BMI to have a
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14. record of gastroesophageal reflux disease/Barrett esophagus.And they are related with an
higher risk of oesophageal adenocarcinoma.
Co-relation between obesity and pancreatic cancers.
Modern studies have identified a little increase in risk of pancreatic cancer among individuals
with high BMI than the normal individuals. But the mechanism is not clear how the co-
relation of overweight and obesity with pancreatic cancer development.
also some studies shows that there is an increase in mortality rate with pancreatic cancer
patients who are obese(14) .
Co-relation between obesity and thyroid cancers.
Individuals with high BMI has been found to be associated with higher risk of thyroid cancer.
It is not clear how this association develops.
Co-relation between obesity and gallbladder cancers.
The risk of gallbladder cancer is higher when the BMI is higher than the healthy range(15).
The increase in risk may be due to the higher frequency of having gallstones in obese people
this is a risk factor for gallbladder cancers(15).
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15. Co-relation between obesity and other types of cancers.
The link between having high BMI and prostate cancer has been studied in deep, so when the
statistical data from numerous studies are pooled, analyses present that obesity may be
associated with a very little increase in the risk of having prostate cancers due to obesity.
the bio medical link between the risk of prostate cancer and obesity is the higher levels of
some hormones and growth factors, a major example is IGF-1.
Also some other studies have shown a poor link between obesity and risk of having an
ovarian cancer, specially in premenopausal females, But other studies haven’t found an link
between them. As like as some other cancers, the link between ovarian cancer and increased
BMI may explained with the increased levels of estrogens.Also there are suspicions for
association of obesity to liver cancers and to some species of leukemia and lymphoma.
so now we can understand that there is a clear link between obesity and the cancer risk.the
next problem is how to overcome this and how to reduse the cancer risk.as result of
thousands of studies in this field medical professionals suggest that, it is a possibility
of reducing cancer risk by reducing obesity.in the following section I will what are the
treatments for obesity.
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16. Treatments for Obesity
Treatments for obesity mainly depend on reducing energy input below energy loss and
making a relatively sustained negative energy balance until the needed weight loss is
gained,or simply reducing energy uptake or increasing energy loss. To reduce energy uptake,
most "reducing diets" are created to contain big quantities of “bulk”,that typically consist of
non-nutritive cellulose or other substances which are cannot be digested.
also ther are various drugs for reduce the degree of hunger and appetite as a treatment of
obesity.The most commonly used drugs are the amphetamines (or amphetamine
derivative),these drugs directly inhibit the feeding centers in the human brain.One such drug
in use for treating obesity is sibutramine, it is a sympathomimetic which decrease food uptake
and also increases energy wastage.But ther is a dark side in using these drugs,because these
drugs can overexcite the central nervous system(CNS), making the patient nervous and rising
the blood pressure.Also,when the time passes patients adapt for the drug, so that weight
reduction is usually a less amount,not higher than 5% to 10%. Also there is a another group
of drugs effect on lipid metabolism.As a example,orlistat,this is a lipase(enzyme that digests
lipids) inhibitor, decrease the intestinal digestion of lipids.As result of this a considerable
portion of the taken lipids with food is loss with the feces and as a result decreases the energy
uptake.but this drug also has some disadvantages,as a example fat loss with fecal matter may
result in unpleasant gastrointestinal side effects, also there is a waste of fat-soluble
vitamins( vit - A , vit - D , vit - E , vit - K ) with the feces.
Also a patient can achieve a significant weight loss by increasing physical activity. The
morephysical exercise one gets, the energy expenditure become greater and as a result obesity
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17. reduce. Therefore,physical exercise is an essential part of any treatment for obesity.So the
modern clinical methods for the treatment of obesity highlights that the 1st step be lifestyle
changes which includes increased physical exercises combined with a decrease in energy
(food) intake. For morbidly obese patients with BMIs higher than fourty, or for patients with
BMIs greater than thirty-five and with complications such as type II diabetes or hypertension
that predispose them to other serious disease conditions,there are variety of surgical methods
are to use for reduce the fat mass of the body or to reduce the quantity of food that a person
can taken at each meal. Two of the most common surgical procedures used in the world as a
treatment for morbid obesity are
1 ) Gastric bypass surgery.
2 ) Gastric banding surgery.
Though these surgeries produce a considerable weight loss in obese and over weight
patients,these are major operations, and also there may be long-term effects on overall health.
Summary
obesity is a major health problem in the modern world and it causes many ill effects on
human life. As there are clear connections between obesity and other diseases obesity plays a
major role in carcinogenesis. Because of that we can reduce cancer risk in society by
controlling obesity and adapting to a healthy lifestyle.
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20. Acknowledgement
I wish to thank our dear sir Dr.Mahinda Kommalage for all the advices and
his valuable time in completing this analytical essay.
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