Few topics evoke greater sense of apprehension than the word cancer. Everyone knows what it is, and no one wants to get it. The question is: are we doing enough to prevent it?
Prevention is about stopping cancer from developing in the first place - it is not the same as early detection. For example, detecting a breast lump while it is still small is called early detection. Prevention refers to stopping the process way before it starts, almost like what Arnold Schwarzenegger’s ‘Terminator’ tries to do: go back in time and change things so the future is better. While early detection is possible for many cancers, only very few cancers are genuinely preventable, and colorectal cancer is one of them.
James Cameron’s The ‘Terminator’ tries to go back in time and change things for a better future. An idea closely related to cancer prevention.This article describes the fascinating mechanisms of how a healthy cell turns into cancer, followed by a discussion on strategies to prevent colorectal cancer, which is currently ranked no.2 in the world among lethal cancers.
What are the symptoms of bowel cancer?
As the large intestine is a wide-bore elastic tube and the cancer is tiny to start with, symptoms do not occur in the early stages. As the lump grows in size over the years, there may be blood in stool, change in bowel habits or a sense of incomplete evacuation.
Fortunately the vast majority of people with such symptoms turn out not to have cancer. In other words, these symptoms cannot be relied upon when searching for colorectal cancer. As a result, diagnosis is often delayed.
Many people with delayed or missed diagnosis of cancer will give a history of having been erroneously diagnosed as haemorrhoids (‘piles’) several years prior. Unfortunately, such patients are often not adequately investigated with colonoscopy, which could have caught the cancer at a much earlier stage.
Why does someone develop bowel cancer?
Most people are aware that cancer occurs more commonly in certain families, and also among those with certain lifestyles more so than others. While this is true, a large number of cancers occur even among people who have a healthy lifestyle with no family history. That is because cancer is predominantly a disease that originates in the DNA. Lifestyle and environmental factors account for only one-third of the cancer burden worldwide.
The lining of the large bowel is particularly susceptible to cancer because of its high cell multiplication rate – a process so rapid that the entire mucosal lining gets renewed every five days.
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Colorectal cancer is the end-result of progressive abnormalities of the cell DNA, some of which may be inherited or spontaneous, while others are caused by environment – by both known and unknown factors. Known lifestyle factors include alcohol use, lack of adequate fiber in diet, along with excess intake of red meat, saturated fat and processed meat. Bowel cancer occurs more commonly among those who are obese or diabetic. Increasing age is the most consistent risk factor for colorectal cancer, the risk increasing with each passing decade above 40.
The role of genes in bowel cancer.
DNA is a long and coiled thread located inside the nucleus (core) of the cell. It is made of nucleotides that are strung together in a purposeful sequence, short segments of which are called genes. If our DNA was a gigantic novel, our chromosomes comprise the 23 chapters, while our genes would represent only a few paragraphs that mostly describe the manufacture of proteins and cell division. We inherit a copy of each gene from our parents. Each of our 20,000 genes has a role to play in normal health, and when altered, some are involved in cancer.
An error in the DNA sequence is termed a mutation, and this can range in size from a single nucleotide (point mutation), to an entire segment of a chromosome that involves several genes.
Genes that guard against cells turning cancerous are called tumor suppressor genes. The APC gene is a typical example, whose role in health is to regulate cell growth, cell-to-cell interaction and cell death - in short, helping cells stay organized within tissue. Mutation in the APC gene turns off this ‘natural brake’, leading to uncontrolled cell growth. The APC gene has thus been termed the gatekeeper gene for colorectal cancer. As it is a recessive gene, both copies of the gene need to be turned off to cause cancer.
Cancer-causing genes like the K-ras gene are called oncogenes. Under healthy conditions, these genes are gainfully employed in the cell-signalling department, relaying messages from outside the cell into the nucleus about how and when the cell should divide, mature or die. They are called oncogenes because of their ability to be turned on into cancer-inducing genes by mutation. Such mutations result in the cell-signalling switch being stuck permanently in the ‘on’ position, leading to uncontrolled cell multiplication. As they are dominant genes, mutation in only one copy will be enough to cause cancer.
In addition to oncogenes and tumour suppressor genes, there are also the so-called stability genes, which protect us by preventing mutations from happening in other genes. These genes basically function as maintenance workers who instantly repair any inadvertent error that creeps in during normal DNA replication process. Examples include the MMR (mismatch repair) gene. When such genes malfunction, they can accelerate cancer formation simply by allowing mutations to happen.
Many mutations are inherited. Others occur spontaneously as the cell repeatedly divides, or are caused by environmental factors. In fact, it takes a lot of steps for a cancer to successfully develop – several mutations and genetic abnormalities have to first accumulate in tissue, each time escaping the body’s natural defense mechanisms.
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As the colony of cancer cells enlarges into a tumour, it gradually builds its own food and oxygen supply by recruiting new blood vessels, soon invading surrounding structures and later spreading to distant sites.
What is the role of diet in colorectal cancer?
Though traditionally, bowel cancer has been linked with consumption of red meat, some large studies have shown similar cancer rates among vegetarians and meat eaters. Greater intake of saturated fat and processed meat such as bacon and ham are linked with bowel cancer. Ingestion of fish offers some degree of protection. Though it would be tempting to believe that a fiber-rich diet with plenty of fruits and vegetables should help reduce colorectal cancer risk, several studies have refuted it.
Some of the earlier studies that linked dietary factors with cancer have been found to be flawed due to recall bias, a common problem with studies of case-control design. Recall bias occurs when a researcher asks a pointed question such as “Did you ever take a lot of red meat in your diet?”
A cancer sufferer will be more likely to admit things such as high red meat and low fiber intake, as they would have been asked this question by several others prior as part of their cancer workup, and is already suffering from a sense of guilt. Thus, in comparison, a cancer patient is more likely to admit to higher meat intake, compared to a healthy person.
As obesity and diabetes are linked with several cancers including colorectal cancers possibly by the effect of insulin-related growth factors on cells, it is prudent to maintain a healthy body weight by limiting intake of sugary and fatty foods.
There is also published evidence that those who migrated from low-incidence areas to high-incidence areas acquire the cancer risk of the new region. This could be an effect of the acquired diet and lifestyle. It could also be an apparent increase in the number of otherwise silent cancers discovered due to greater access to colonoscopy as part of better healthcare facilities.
How has colon cancer been curbed by the western nations?
Celebrity news anchor Katie Couric appears on the cover of TIME magazine for her effort in colorectal cancer prevention.Thanks to effective public health intervention in the past two decades, the number of deaths from colorectal cancer has finally started to come down in western nations.
The first step towards defeating it was to build awareness about this cancer. Visual and print media played a major role in this, with celebrity news anchor Katie Couric spearheading the campaign by appearing live on national TV in the US while undergoing a colonoscopy herself. As a result, the procedure was watched simultaneously by millions of people. Katie took up this cause after her husband became a victim of colorectal cancer in 1998, and she realized that is was a preventable disease. This single daring move not only increased public awareness, but also reduced the stigma about undergoing such an examination.
Doctors noted that the chance of developing bowel cancer was greater with advancing age. As most bowel cancers start as small benign lumps called polyps, doctors figured out that removing a polyp before it got a chance to turn into cancer was by far the best strategy to prevent colorectal cancer.
Colonoscopy allows detection and removal of polyps, preventing colon cancer in the long term.What is colonoscopy?
Colonoscopy is a bedside test that is performed by inserting a long, thin rubber tube with a lighted tip and camera through the rectum after washing the bowel clean. The tube is then manoeuvred through the large intestine while the walls are carefully examined. With adequate sedation, pain medication and skill, it can be done without discomfort to the patient as an outpatient procedure. Polyps, when seen, can be safely removed without the need for surgery.
Colonoscopy is usually done to evaluate certain symptoms of the digestive tract such as bleeding and change in bowel habits. When performed in a person without symptoms with an aim to search for and eliminate polyps, it is called a screening colonoscopy.
Not all polyps grow into cancer. However, most colorectal cancers start off as precancerous polyps which are initially too small to cause symptoms. Adenomatous polyps are traditionally called precancerous polyps. As they grow, more DNA changes occur, becoming genetically more abnormal and unstable. Those that are larger than 1 cm in size have a much greater chance of cancer, and are called advanced adenomas.
Though the polyp grows slowly at first, once it turns cancerous, it grows rapidly, invading deeper layers of the bowel wall and spreading to neighboring organs. It may spread to faraway places such as the liver. This is called metastasis. Treatment of colorectal cancer requires an operation, followed in selected cases by chemotherapy and radiation. The chance of survival depends on the stage of cancer at the time of diagnosis. What is impressive is that the need for such major interventions can be eliminated by undergoing a screening colonoscopy ahead of time. This is a classic example of the phrase ‘a stitch in time saves nine’.
The polyp-cancer sequence.
In the natural history of colorectal cancer, intervening early can result in complete cure, even without an operation.As polyps take about 5-15 years to grow to cancer, removing them ahead of time is the most effective preventive strategy at this time. Once the polyp is removed, its biopsy test report will give an indication of its cancer potential. If there is malignant potential, a repeat examination will be required after a few years. In addition to polyp detection, screening colonoscopy also allows early detection of cancer in a few instances, which improves the chance of complete cure.
Less effective alternatives to colonoscopy include sigmoidoscopy (a partial examination of the large bowel, often criticized as being similar to performing mammography of only one breast, as the other half remains untested) and CT colography, the latter unfortunately necessitating a subsequent colonoscopy to remove any polyps found.
As large numbers of healthy people over the age of 50 underwent screening colonoscopies from the late 1990’s, there has finally been a decline in the number of new colon cancer cases in the western nations in recent years.
What is screening?
Screening involves performance of a diagnostic test in a person before the onset of symptoms, in an attempt to reduce the future risk of death from that disease. Naturally, one might wonder why not perform all tests on everyone so that no one ever gets a disease. The answer to this question was detailed in my earlier article on lab tests -- clearly, not all tests should be done for everyone.
For a disease to be considered worthy of screening, it must fulfil certain criteria. First, it must be common, as screening for rare diseases isn’t worth the effort and expense involved. Second, the test must be easily available, safe and economical. Third, the test must be able to detect the disease sufficiently early so that cure is possible. Fourth, there must be proof that doing the screening test will reduce the death rates from this specific disease.
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Bowel cancer satisfies all these criteria, and that is the reason why developed countries recommend screening colonoscopy for all their citizens. They reckon that the cost of screening is less than the expense incurred in treating disease at an advanced stage, not to forget the added years of good-quality life for the patient.
Needless to say, those who experience the symptoms of large bowel origin discussed above should consult a doctor regarding the need for colonoscopy to ascertain the diagnosis. This cannot be considered ‘screening’ as it is done for evaluation of a worrisome symptom.
What is the Indian scenario? Who should get a colonoscopy to check for polyps? What is the global standard?
American guidelines advocate the first screening colonoscopy at age 50 for Caucasians and at least every ten years thereafter, while for African-Americans, starting at a younger age is recommended. Canadian, British and European screening guidelines are similar, with mild regional differences.
Though already established as standard of care in parts of Asia such as China, Taiwan and Singapore, screening colonoscopy is not widely practised or recommended in India at this time. There is a perception that colon cancer is less common in India. However, it is difficult to directly compare the occurrence rates in India with that of developed nations because of scarce local published data and limited access to colonoscopy among the communities surveyed.
Though an individual’s risk of developing colon cancer is higher when there is a family history of cancer, it is worth noting that over 70 percent of colon cancers occur in people with no such family history. Therefore, opting to screen only those with an established family history will miss the majority of cancers.
It is known nevertheless that undergoing a thorough, good-quality colonoscopy will reduce the person’s future risk of colon cancer by about 60 percent. For those who are interested, the age of opting for colon cancer screening in India is yet to be determined. Studies from India have reported a sharp increase in the risk of polyps as well as colorectal cancer by age 40, therefore it would seem a reasonable age to undergo individual screening, although no community guidelines exist yet.
At this time, in India, screening colonoscopy remains an optional test for those who would like to minimize their own individual risk of colon cancer, particularly when there is a family history.
In summary, colorectal cancer is one of the few genuinely preventable cancers. There is no guarantee that a healthy lifestyle or a clean family history protects against colorectal cancer. As symptoms only occur late during the course of the disease, it makes sense to undergo preventive checkups around middle age while still in good health, rather than wait for symptoms to appear. Though symptoms are rather unreliable in predicting a diagnosis, bleeding during a bowel movement should not be ignored.
Further reading
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252065/
4. Vegetarians have same colorectal cancer rates as meat eaters: results of a large British study
5. Link between processed meat and bowel cancer
6. Link between obesity and cancer
7. The molecular mechanisms of colorectal cancer
8. The role of immune system in colorectal cancer
10. US preventive services task force guidelines on screening for colorectal cancer
11. Younger age for screening for African-Americans
12. Trends for younger people to develop colorectal cancer in India
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001346/
13. Colon polyps more common over age 40 in India
14. Recall bias and other types of bias that contaminate conclusions of research
15. Just one colonoscopy in a lifetime can protect against colon cancer
(The author is a senior consultant gastroenterologist and deputy medical director, Sunrise group of hospitals)
