UNDERSTANDING CANCER

UNDERSTANDING CANCER

 

The word ‘cancer’ is an umbrella term referring to about 200 known diseases affecting humans, of which the name is so given based on the location/part of the body where it  starts – eg. breast cancer - breast, stomach cancer - stomach etc.  

 All these diseases have two common characteristics:

  1. an uncontrolled growth of cells and
  2. the ability to invade and damage normal tissues either locally or at a distant site of the body.     

To understand cancer, it's helpful to know or understand to a certain degree how a normal cell becomes a cancerous cell, how it develops and spreads through your body.

 2.1 Life cycle of cell

 The beginning of life

 We all begin life as a single cell (a fertilized egg) in the womb.  This single cell multiplies and forms communities of cells (trillions of them), which specialize into many different cell types in the body during early growth depending on which function they perform eg. brain cell, blood cell, etc.  

 All our bodily functions are carried out by cells and these cells communicate with each other, carry out self- repair and self- regulation.   Both normal and cancerous cells are produced and destroyed all the time.

 Our body produces millions of new cells every minute and these new cells develop from pre-existing cells through a process of cell division called ‘mitosis’ and between 500 and 700 billion cells die each day due to ‘apoptosis’ (programmed cell death). 

 During the early years of a person’s life, normal cells divide faster to allow the person to grow.   After the person becomes an adult, most cells divide only to replace worn-out or dying cells or to repair injuries.

 Do note that along with the normal cells, ‘abnormal’ cells are sometimes produced in the body and this is no cause for alarm. 

 2.2  Difference between ‘normal’ and ‘abnormal’ cells

 Simplistically, the main difference is that normal cells are programmed to live and after a certain time (ranges from days to months) will undergo ‘apoptosis’ - a     programmed cell death which follows a controlled,  predictable routine.  When this occurs, the old cell will be replaced with a new one. 

 However, in ‘abnormal’ cells, due to a series of changes (mutations) in the cell they are damaged and cannot be destroyed through this normal process.  These     disturbances in its cellular functioning may cause it to become cancerous – especially if the terrain is conducive.

 A few ‘abnormal’ cells within the body do not cause immediate damage for they need time and resources to build into a dangerous mass and this can take anywhere between 1 – 40 years.  In addition, when our immune system is healthy, it is able to detect and destroy these aberrant (abnormal) cells just as it does with invading viruses and bacteria, thus preventing the cancer cells from overwhelming the body. 

 However, if our immune system is weak, these cancer cells can slip through the defense system and begin to multiply uncontrollably and induce formation of new blood vessels to supply the required nutrients to the cancerous mass.  Initially they grow where they first occur, but  small clumps can break off and travel in the blood or lymph system to other parts of the body and grow there.  When this happens, it is called ‘metastasis’ or circulating tumor cells.

 2.3 The onset of cancer

 Cancer is first and foremost a disease of the cell; the smallest and the most fundamental component of the human body.  The onset of cancer is a  gradual phenomenon, evolving quietly over a period of time before symptoms appear. 

Broadly, we can divide the development of cancer in 4 steps: initiation, promotion, progression and metastasis (spreading).  

 Stage 1 - Initiation

 In the initiation stage, some kind of a change is happening in a cell that   begins the carcinogenic or mutation process.  Although there are many kinds of cancer, all cancers begin with ‘abnormal cells’ that grow out of   control.   How does ‘normal cell’ become abnormal?  It becomes ‘abnormal’ because of the  damage to its DNA* or the adaptation changes within the cell to the environmental influences (survival mechanisms).

 *DNA (deoxyribonucleic acid)  is the   genetic ‘instruction manual or the blue print’ found in all the cells. 

 What causes ‘damage DNA’ or  the adaptive changes?

 Our cell is under constant bombardment and damage can occur.  The damage to the cell can   occur in the following ways:

 randomly, caused by mistakes in the normal DNA replication

  • inherited genetically
  • exposure and contact with viruses and carcinogenic substances such as free radicals, ionizing radiation and chemicals in smoke or things we eat.

 In a normal cell, when the DNA/ cell is damaged the cell either repairs itself or goes into suicide mode.  Abnormal cells are also destroyed by our immune system.   However, when the ‘abnormal’ cells are not repaired and they do not die, they develop mechanisms to evade the ‘immune system’. They will live on, multiplying and making an army of ‘abnormal cells’.   These abnormal cells may not be cancerous at this stage – but they could potentially be, given the chance.  

 The ‘abnormal cells’ remain vulnerable; only some will succeed in progressing further and to achieve these, there must be ‘factors or conditions’ that promote proliferation (or growth).   In most cases, the damaged cells may form a tumor (see insert on page 14 for more on tumor).  Over time, the tumors can replace normal tissue and form lumps or swellings.  Some cancers, like leukemia, rarely form tumors. Instead, they involve the blood and blood-forming organs and circulate through other tissues where they grow.

Stage 2 - Promotion

In this next section we will briefly review risk factors that have been well documented over the years as the factors that may trigger the onset of cell mutation, aberrant behavior and promote its growth.  

 Factors that can trigger and promote cancer

  We all have a risk of developing cancer and some have more risk than others.  Understanding the factors that promote the development of cancer is crucial to enable us to acquire an increased    understanding of the cell’s behavior as well as to formulate strategies for treating it. 

Almost everyone knows that smoking can cause cancer, but very few people realize that daily activities such as eating and lack of physical activities can also result in cancer. 

Intriguing  scientific research has shown that our risk in developing cancer actually depends on a combination of genes, environment and also lifestyle.  Despite popular belief, only about 5% of cancer incidence is attributable to genetic defects while the remaining 90–95% actually have their roots in the environment and lifestyle.  While a cellular mutation may be the beginning of the   cancer process, the underlying mechanisms that initiate the cascade of molecular events that lead to the growth and aggressiveness of cancer is inflammation*, caused by the interaction of our genes within their environment. 

 Various factors which increase inflammation in the body include carcinogens (cancer causing agents) from tobacco, alcohol, diet (excess or lack of), obesity, infections, radiation (both ionizing and non-ionizing), stress, emotion, lack of physical    activity, substance exposure at work, insulin like growth hormone, environmental pollutants and other factors.  Insulin like growth hormones can also play a key role in ‘damaged cells’ proliferation.

Regular or prolonged exposure to the above ‘factors’ enables the damaged cells to gain characteristics which render the cells more malignant. 

 * Inflammation is the body's response to any tissue damage, be it caused by injury, infection, exposure to toxins or other types of trauma.  The body's inflammatory response (swellings, redness, tenderness) triggers immune responses that result in repair of the damaged tissue, and begin the healing process at the site of the injured tissue. 

Table 1—The percentage contribution of the various  factors to cancer is as shown below:

RISK FACTORS ASSOCIATED WITH CANCER 

*The lower percentage has been taken, except alcohol the original data was 4-6%

Source:  National Center for Biotechnology Information - Cancer is a Preventable Disease that Requires Major Lifestyle Changes 2008 July 15 – read more at

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515569/

Genetically or epigenetically influenced, what is your take?

 Let’s remind ourselves that historically cancer was a rare disease.  It is only in the early part of the twentieth century that cancer has increased dramatically, especially in industrialized nations.  For example, cancer occurrence in America in the early 1900s was rare and affected only 3% of its population, yet right now almost one in three Americans will be diagnosed with cancer in their lifetime1.   In Malaysia, it is estimated that one in four Malaysians (1:4) will develop cancer by the age of 75 2.  A  disease once associated with the affluent nation is now increasingly common even in developing countries like Malaysia.

 Your view and belief on the role of genetics in the evolution of cancer is crucial because it affects your  perception and subsequently how you prevent/ treat cancer. 

 Genetically oriented? 

 Those in this school of thought will likely be looking to the human genome for solutions to most chronic illnesses, including the diagnosis, prevention, and treatment of cancer. In a recent high profile case, the famous American actress Angelina Jolie underwent a double mastectomy after she was found to be carrying the ‘faulty’ BRCA1 gene, giving her an estimated 87 per cent chance of developing breast cancer and 50 per cent risk of developing ovarian cancer.   Her belief in genetic science caused her to remove her pair of normal breasts to reduce the risk of cancer.   A believe that genes are the cause of cancer renders us  powerless against the disease and the way forward is to target the malignant cell with chemo and radiation, along with surgery to remove the cancerous cell or tissues that may potentially become cancerous.

 On the other hand, many reputed studies have revealed that 90-95% of cancer cases are actually linked to lifestyle and environmental factors (epigenetics).   These studies have indicated the relative significance of certain lifestyle factors such as smoking, poor diet, obesity, drinking and etc. increases the risk not only of cancer but also of a range of other serious chronic conditions such as cardiovascular diseases and diabetes.  When we accept that the vast majority of cancers are not caused by genetic defects it means that in most cases we have the power to modify or eliminate most of the factors that lead to it.

 For example, the one thing we know for sure is that obesity increases the risk of a number of different types of cancer.  For example with hormonally driven cancers such as breast cancer, obese patients have a worse  prognosis.  Therefore, to reduce the risk of developing breast cancer (even for women with BRCA1 and BRCA2 genes) is to control their weight, improve their nutritional status and to exercise regularly.  

 Believing that you are in control of the situations that affect your body will provide you with far more opportunities to prevent and treat cancer. 

Genes have very little impact on life outcomes3

 After sequencing his own genome, pioneer genomic researcher Craig Venter remarked at a leadership for the twenty-first century conference that “Human biology is actually far more complicated than we imagine. Everybody talks about the genes that they received from their mother and father, for this trait or the other. But in reality, those genes have very little impact on life outcomes. Our biology is way too complicated for that and deals with hundreds of thousands of independent factors. Genes are absolutely not our fate. They can give us useful information about the increased risk of a disease, but in most cases they will not determine the actual cause of the disease, or the actual incidence of somebody getting it. Most biology will come from the complex interaction of all the proteins and cells working with environmental factors, not driven   directly by the genetic code”

Stage 3 - Progression

 At the progression stage the damaged cells override the normal signaling system that regulates their growth.  They continue to reproduce rapidly, form new vessels by angiogenesis and refuse to die. 

 Stage 4  -  Metastasis

 Metastasis is the spread of cancer to the other locations in the body and is very common in the  later stages of cancer.  It can occur via the blood or the lymphatic system or both.  The cancer that a patient begins with, becomes very different in the later stages; more mutated and difficult to treat.

 2.4      Classifications of cancer

 Cancer classification is generally made according to the site of origin of the malignant cells.  Here are some common examples of site of origin classification.  ( not an exhaustive list )

Carcinoma          :  Cancers arise in the epithelium (the layers of cells covering the surface of the body and the lining of internal organs and various glands)

Sarcomas           :  Cancers originating from the supporting/ connective tissues of the body, such as bone, muscle, cartilage, fat and blood vessels.

Leukemias          :  Cancers involving blood and blood-forming organs such as bone marrow, lymphatic system and spleen

Lymphomas        :  Cancers originating from the lymphatic glands and systems

Gliomas              :  Cancers of the nerve tissue

Melanomas          :  Cancer of the skin

Myeloma             :  Originates in bone marrow

Blastoma             :  Originates in embryonic tissue of organs

Adenocarcinoma  : Originates in glandular tissue

Leiomyosarcoma  :  Originates in smooth muscle

Neurosarcoma     :  Originates in the nerve cell

Liposarcoma        :  Originates from fat cells

 Tumor or cancer?

2.5         Tools for finding or diagnosing cancer

 Some people panic upon finding out that they have lumps but some fail to get proper treatment because they dismiss  a simple lump as not cancerous.  

 Are all lumps or swellings cancerous?   Not necessarily.

 A tumor is basically a swelling, a mass, lump or lesion formed in your body by an abnormal growth of cells.  It can be:

 ¨ benign (non-cancerous)

¨ pre-malignant (pre-cancerous or a growth that is probably harmless at the moment but does have a significantly increased risk of cancer.

¨ malignant (cancerous).

 Example of benign growth would be ‘lipoma’, the fatty encapsulated lumps  beneath the skin of the arms, neck or back, unsightly but do no harm.  For women, lumps may also be noted in the breast tissues especially before their  menstrual cycle, these usually disappear after a few days.    

 Although benign tumors are mostly    harmless, some may have negative health effects, such as pushing against vital    organs or blood vessels or overproduction of certain hormones.  Due to this, benign tumors may still need to be removed via surgery.  Removing a benign tumor is   relatively easy through surgery, and that’s it - the condition does not recur.

 The way to check if a tumor is cancerous is through a BIOPSY, a procedure where a small sample of tissue from the mass is taken and a series of tests performed to determine if the tumor is cancerous.

 Tools for finding or diagnosing cancer

 ¨ Ultrasound — the use of reflected high-frequency sound waves to examine tissues of the body;

 ¨ Biopsy — removal of a small piece of tissue, which is looked at under a microscope;

 ¨ X-ray — producing an image by passing x-rays through the body;

¨ Computed tomography (CT) — the use of x-rays to produce a cross-sectional picture of body parts; and

¨ Magnetic resonance imaging (MRI) — the use of magnetic fields and radio waves to show changes in soft tissues without the use of x-ray

 Mammogram, Ultrasound, X-ray, CT, and MRI are all painless and noninvasive; however, having too many CTs or x-rays can increase your risk of developing cancer because they expose you to radiation.   Other tools for finding and diagnosing cancer or abnormal cells that may become    cancer include Pap tests, which look for abnormal cervical cells; HPV DNA tests, which look for DNA from cancer-causing HPV types in cervical cells; fecal occult blood tests (FOBT), which check for blood in the stool; sigmoidoscopy,which examines the lower colon; and colonoscopy, which examines the entire colon. Some people choose to do self-exams, such as feeling around their breasts or testicles for new lumps or looking over their skin.   If you notice anything unusual, consult your doctor.

 In summary, when you have cancer, irrespective of where it shows up; the cause is the same – malfunctioned cells or cells that refused to die.  While some of us may be unfortunate enough to carry the ‘cancer gene’, it is important to know that this incidence is relatively small ie. 5 - 10% and that these genes may not be ‘activated’ in an environment which is not favorable to their growth.  By and large it is the ‘epigenetic’ factors that are hugely responsible for the increase in the cancer incidences. 

 What if I have a gene associated with cancer?  Firstly, it does NOT mean that you will definitely get cancer.  It simply means that it is a risk factor.  It is similar to the other non-genetic risk factors like smoking, toxin exposure or diet—the strategy is to make preventive lifestyle and behavioral changes that discourage the expression and/ or the growth of the cancer cells.

 Sources of carcinogens ( and therefore damage to cells ) turn up in things that we least expect;  detoxification is therefore imperative to maintain optimal health. 

 

Sources: 

      1. American Institute of Cancer Research. 

  1. National Cancer Society Malaysia).
  2. 'Genes have very little impact on life outcomes' - Dr. J. Craig Venter Pioneering Genomic Researcher

 

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