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Colorectal Cancer

Apr 09, 2021

Cancer remains one of the top causes of mortality in the developed world. The incidence of cancer globally shows no signs of abating. The Globocan project by the International Agency for Research on Cancer reported about 12 million cancer cases reported worldwide in 2008 resulting in about 7 million deaths . More than half of these occur in the economically developing world.


Breast cancer is the leading cancer diagnosed in females whilst lung cancer is the commonest malignancy detected in males. The pattern of incidence differs between the developing world and the economically developed one. Lung, colorectal and prostate cancers are predominant in males in the developed countries. Their female counterparts are afflicted by breast, colorectal and lung cancers. In the developing countries, cancers of the lung, liver, stomach, and cervix are more common.

Colorectal Cancer

Colon and rectal cancer is the second most commonly diagnosed cancer in females worldwide. In males, it is ranked number three. Over 1.2 million new cases are estimated to be detected each year, resulting in about 600,000 deaths. Incidence rates are highest in Australia, Europe and North America. There is a male preponderance in most countries. Of note is the fact that the rapidly increasing incidence is in areas historically deemed as low-risk. These include eastern Europe and certain parts of Asia, where the rates have even exceeded the peak incidences observed in the United States and Australia.


Death rates have been noted to be decreasing in most of these western countries and this is believed to be a result of improved treatment, increased awareness and early detection. Proven modifiable risk factors include smoking, excessive alcohol consumption, physical inactivity, obesity, and red and processed meat consumption.


Singapore belongs to one of the Asian countries where the incidence of colorectal cancer has reached that of the West. It has become the top ranked cancer in men and women combined. As a result of this disturbing trend, the Ministry of Health has increased its efforts to promote screening to the population.


The vast majority of colon and rectal cancers arise from adenomatous polyps. The transformation of these adenomatous polyps (adenoma-carcinoma sequence) to cancer has been shown to take 5 to 10 years. This occurs following a series of multiple gene mutations. The key essence is that these adenomatous polyps are relatively asymptomatic. They are present in up to 25% of individuals at the age of 50 years and its prevalence increases with age. More than 90% of these polyps, if detected by screening modalities, can be removed from the colon without the need for surgery.


This detectable premalignant phase (adenoma), coupled with a relatively long duration of malignant transformation, forms the fundamental basis for screening as an effective means of preventing colon and rectal cancer. Mortality can be reduced simply by screening asymptomatic individuals for the presence of adenomas and early cancers. Studies in medical literature have demonstrated that the number of early staged colorectal cancers detected have doubled just by instituting an effective screening programme. Reduction of mortality rates of between 15 to 30% have been reported.


The paradigm in screening for colon and rectal cancer has shifted from ‘early detection’ to PREVENTION.

When should screening commence and who should be screened ?

Screening in an individual of average risk should begin at the age 50 years. This is based on the fact that the risk increases sharply after this age. Screening should commence earlier in increased and high–risk individuals. The age of commencement is dependent on the risk factors present. Increased-risk individuals include those with a personal history of colorectal neoplasia, one or more first degree relatives with a history of colorectal cancer, or a personal history of breast, endometrial, ovarian cancers. High–risk individuals are those who possess a hereditary or inherited predisposition to developing colorectal cancers. These include those who have a family history of one of the polyposis syndromes. Although uncommon, patients who suffer from a long history of ulcerative colitis are also considered high risk.

How to screen for colorectal cancer ?

For a screening test to be widely applicable, it must be inexpensive, reliable and acceptable. Various screening tests for colorectal cancer have been reported.


Faecal occult blood testing (FOBT) is the only screening modality that has been shown in 3 large randomized trials to show a 33% reduction in colorectal cancer mortality. In light of this, there is very little reason not to offer FOBT screening for average-risk individuals aged 50 years and above at the very least. It is important to note that the early studies mentioned above made use of the guaiac based kit which has been shown to have a 60-70% sensitivity for cancer and only 25-50% sensitivity for polyps.


Nowadays, most FOBT kits utilize the faecal immunochemical test (FIT). This has been shown to be more sensitive and technologically superior. The hallmark of this is that it is specific for human globulin, thereby reducing the incidence of false positives from red meat ingestion. It is more specific for sources of bleeding in the lower gastrointestinal tract. To top it off, the method of collection is far simpler and should increase compliance. Comparisons between FOBT and FIT have shown the latter to be superior in sensitivity for both cancers and polyps. The recommendation for FIT is for 2 separate samples to be taken on 2 separate days.


A positive FOBT or FIT mandates further evaluation with optical colonoscopy.

Optical colonoscopy

This is the only test that allows for the direct visualization of the colonic mucosa. It is by far the most accurate means of diagnosing colon and rectal neoplasia and serves as the gold standard by which all other screening modalities are referenced. The main advantage of colonoscopy is the fact that it remains the only means by which polyps can be removed at the same sitting as the diagnostic procedure. The removal of these polyps essentially prevents them from ever developing into cancer. Another benefit of colonoscopy is the long recommended screening interval of 10 years.


Pre-procedure bowel preparation usually takes 1 of 2 forms: 1) high-volume (3-4 litres) polyethylene glycol (PEG) or 2) low-volume (90 mls) oral fleet. Oral fleet is contraindicated in patients with renal impairment due to its high phosphate content. For suitable patients, it is a more palatable option as it can be mixed with sweetened fluids. Patients taking oral fleet must be encouraged to drink plenty of water to decrease the likelihood of phosphate toxicity.


The reported miss rates for optical colonoscopy is 6-12% for large adenomas and 5% for cancers. More often than not, it is the small, flat polyps that are missed. New imaging modalities such as chromoendoscopy, narrow band imaging and other adjunct technologies have been developed to increase and improve the yield of polyp detection during the procedure.


The screening interval for colonoscopy is dependent on the findings at the index procedure. The 10 year interval is applicable only if there were no neoplastic lesions found. This interval drops with increasing numbers and complexity of the polyps detected. Colonoscopy is the only screening test that combines detection with prevention by polypectomy.



A note on flexible sigmoidoscopy should be made. Its main difference is that no prior mechanical bowel preparation aside from fleet enemas is required. Its effectiveness is based on the assumption that two-thirds of polyps and cancers are located within the reach of the sigmoidoscope. It is prudent to note that about 60% of advanced neoplastic lesions are not associated with a distal lesion. Hence, the recommendation is that sigmoidoscopy should be combined with faecal occult blood testing for better detection.

Computer Tomographic Colography / Virtual Colonoscopy

Virtual colonoscopy is a minimally invasive imaging examination using a new radiologic technique to generate images of the colon and rectal wall. Rapid advancements in this technology, including multi-detector CT, thin slices, software improvements and techniques such as stool tagging with barium or contrast agents, have made this the best available imaging test if optical colonoscopy is contraindicated or incomplete. There is however still the existing concern with the risk of cumulative radiation if used repetitively for surveillance.


Full mechanical bowel preparation similar to that for colonoscopy is still the main requirement. More importantly, there will still be a need to undergo optical colonoscopy to rule out suspicious lesions and for therapeutic polypectomy. The current recommended interval for this modality is 5 years if the results are normal.

Computer Tomographic Colography / Virtual Colonoscopy

Double contrast barium enema, whilst commonly employed in the past, is no longer recommended as a first line modality for colorectal cancer screening. It is still an option if colonoscopy is contraindicated or unsuccessful.


Stool DNA tests are still not ready for population screening due to the lack of standardized laboratory protocols, the high costs of tests, and the lack of data on appropriate intervals between negative stool DNA examinations.


Lastly, whilst serum carcinoembryonic antigen (CEA) is useful for monitoring tumour burden in patients already diagnosed with colorectal cancer, its low specificity and sensitivity in the diagnosis of colorectal cancer makes it a poor screening tool.

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Dr Dean Koh, a general surgeon who specialises in treating colon and rectal cancer, answers our questions and clarifies 5 common ideas about cancer prevention. 1. Eating less red meat and processed meat reduces the risk of colorectal cancer Is it true that people should eat less meat in general to prevent cancer? Meat is an important source of protein, vitamins and minerals in our diet. It is important to note that the studies in medical literature linking meat to the risk of colorectal cancer all refer to processed meats and red meats. White meats are generally well accepted not to be associated with an increased risk at all. While there is no harm in reducing one's intake of meat in general, what I would advise will be a more pragmatic approach of consuming meats in moderation and leaning more towards white meat as opposed to the red meats. Any form of processed meat (be they red or white) increases the risk of cancer. This is because mutagen and carcinogens are produced when the meats are cooked at high temperatures such as by charcoal grilling. In addition, nitrates/nitrites and salts which are used in processed meat leads to carcinogenic nitrosamines being formed. Mutagens and carcinogens These are substances that increase the likelihood of mutations, or triggers the development of cancerous growths. A mutagen induces change or mutation while a carcinogen induces abnormal growth in cells or tissues. They are not identical terms, but both are significant factors, as mutagen can result in the development of cancer. Carcinogenic nitrosamines in processed meats The World Health Organization (WHO)’s International Agency for Research on Cancer (IARC) categorizes processed meats as a carcinogen, based on consistent data that connects high consumption of processed meat with stomach cancer. But don’t panic just yet. The truth is that nitrates and nitrites are naturally-occurring chemical compounds. They are legally used as preservatives to prevent the growth of harmful bacteria in foods like ham and some cheeses. They are also found in vegetables, which acquire these compounds from the soil they grow in. While nitrates are relatively inert, nitrites are more reactive and can react in the acidic stomach environment and, with the presence of chemicals called amines found in protein foods, form nitrosamines. Nitrosamines can also be created when foods are cooked at high temperatures. Taken in context, there’s no need to swear off processed meats completely. However, it’s also important to understand that high consumption of processed meats is also linked to coronary artery disease, stroke and diabetes. In other words, make it an occasional option rather than a daily one. Is it true that less red or processed meat is better? Or would you suggest going meatless 1 day a week? There is little harm in reducing meat intake, even if it’s for 1 day a week. Replacing meats with fish and poultry is always a good start. Another alternative will be to choose smaller portions of meat or use these as a side dish instead of the main focus of the meal. An often-used guideline to consumption will be as follows: daily consumption of 100g of red meat or 50g of processed meat increases the risk of colorectal cancer by 15 – 20%. You can do the math to determine just how many servings of what proportions that will amount to. Is this recommendation only for processed meat? As mentioned above, reduction in the ingestion of processed meat in the long term will certainly reduce one's risk of developing colorectal cancer. In fact, current evidence supports a 15 – 20% increased risk of colorectal cancer for every 50g of processed meat consumed per day! What do you classify as ‘fat meat’? This is a non-specific term that generally refers to meat that is marbled with excessive fat. The effect of consuming too much of it is more related to the obesity/overweight risks, which is associated with increased incidences of colorectal cancer rather than the carcinogenic effect. Cancer prevention tips While there is no proven way to fully prevent cancer, you can help to stay healthy and reduce your risk by making a few changes to your diet. Eat more fruits and vegetables, in a variety of colours. These, which includes different kinds of beans and legumes, provide essential fibre and a wide range of vitamins, minerals and other nutrients. Maintain a healthy weight. Sometimes, it’s not just how much we eat but what type of food we eat. Some foods are high in calories, such as soft drinks and fruit-based drinks, creamy dressings, and processed foods that contain high-fructose corn syrup. So, eating smaller meals may not be as effective as cutting out soft drinks and processed foods. Try healthier snacks such as fresh fruits, yogurt, and baked instead of fried or sugar-laden treats. Reduce consumption of processed and red. It’s not necessary to eliminate these entirely, but it can help to limit your intake by taking smaller portions, or making it a treat on weekends or special occasions. To maintain a health intake of protein, you can eat more fish, chicken, turkey or beans. Cook your proteins differently. Instead of high-temperature cooking methods such as frying, try baking, broiling or poaching meats instead. 2. Being physically active might reduce the risk of cancer Regular activity is associated with lower risk of many diseases, including colon cancer. In fact, the World Cancer Research Fund identifies body fat and physical inactivity as 2 out of 4 preventable risk factors (the other 2 are alcohol consumption and diet). Regular exercise is not just associated with risk reduction in colorectal cancer, there are clear benefits that this results in reduced rates of premature death and incidence/mortality from various cancers. It is important to note that the optimal intensity, duration and frequency of physical activity needed to reduce cancer risks are unknown, the recommendation accepted by most cancer societies around the world is 300 minutes of moderate activity or 150 minutes of vigorous activity per week. 3. Sufficient intake of vitamin D may reduce the risk of colorectal cancer A healthy vitamin D intake is said to reduce the risk of colorectal cancer and increase survival rates for those already affected by colorectal cancer. How does healthy vitamin D levels reduce the risk of colorectal cancer? Vitamin D has an effect on the initiation and progression of colorectal cancer. This is because of its effect on reducing cell proliferation, and stimulating cell death in cancer cells. There have been studies demonstrating an anti-inflammatory effect of Vitamin D as well. The largest studies evaluating the effect of vitamin D are the Nurses' Health Study (NHS) and the Women's Health Initiative (WHI). In general, do women in Singapore lack vitamin D? It's unlikely. This is because of our year-round tropical climate which rarely confines a person indoors for a prolonged period of time. Vitamin D is obtained through skin exposure to UV radiation, through diet (milk and cereal which are fortified with vitamin D) and through supplements. It is important to note that the association between colorectal cancer and vitamin D is not definitively proven, a level of 30ng/ml is generally recommended for not just cancer prevention but for other health conditions. 4. Long-term use of aspirin can lower the risk of colon cancer Is it true that the long-term use of aspirin can lower the risk of colon cancer? Can aspirin be taken as a supplement? The data surrounding aspirin and the reduction of colorectal cancer has proven to be inconclusive. Aspirin has been associated with a reduction in the development of the precursor lesion to colorectal cancer – the adenomatous polyp. However, it must be emphasised that high level evidence for the use of aspirin in healthy individuals in reducing the risk of colorectal cancer is not yet available. Most authorities advocate caution with respect to the use of aspirin in the primary prevention setting simply because of its risk of bleeding. Based on the current available data in medical literature, this cannot be recommended in healthy individuals as a means of prevention of colorectal cancer. Virtually all studies have shown that regular aspirin consumption is associated with an elevated risk of gastrointestinal bleeding and haemorrhagic stroke. 5. A diet rich in garlic reduces the risk of colon cancer Is it true that a diet rich in garlic reduces the risk of colon cancer? How much garlic should a person eat? There is yet little evidence that allium compounds contained in garlic can prevent cancer. All that has been concluded so far is a possible association but these have been predominantly based on preclinical studies. In fact, a recent study involving over 300,000 subjects showed no protective effects as a result of garlic consumption. Article contributed by Dr Dean Koh Reference Q&A on the carcinogenicity of the consumption of red meat and processed meat. (2015, October) Retrieved from https://www.who.int/features/qa/cancer-red-meat/en/ Thompson, R. (2015, 23 October) Red meat and bowel cancer risk – how strong is the evidence? Retrieved from https://www.wcrf.org/int/blog/articles/2015/10/red-meat-and-bowel-cancer-risk-how-strong-evidence
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