Tumour biomarkers are chemicals that are made by tumour cells or other cells of our body, in response to cancer or other benign conditions. Different types of cancers or tumours may be associated with different tumour biomarkers. Colorectal cancer (CRC), which includes colon cancer and rectal cancer is responsible for half a million deaths worldwide every year. There are also about one million new cases diagnosed annually, making it the third most common cancer in the world. Early detection, accurate diagnosis and intensive surveillance are important for best improving a patient's prognosis and response to therapy.
There are a number of methods that doctors use to detect CRC including sigmoidoscopy, colonoscopy and barium enema. Some newer techniques being investigated for effective detection and monitoring of CRC are CT colonography and molecular biomarkers. The use of tumour biomarkers gives doctors a non-invasive way of detecting and monitoring CRC.
Doctors can use tumour biomarkers in the detection, prognosis and management of some types of cancer, including CRC. An abnormal level of tumour biomarker is usually not enough for a complete diagnosis of cancer and is usually combined with other tests such as a biopsy. The type of biomarker detected and its levels can give an indication to what type of cancer may be present, whether or not it is malignant and what the best treatment may be.
Tumour markers are used during the treatment of cancer in order to monitor the effectiveness of a therapy and how the patient may be responding to the treatment. If levels of a tumour biomarker decrease it may mean that the cancer is responding to treatment. If levels remain the same or increase after treatment it may be an indication that the therapy is not working. Continued monitoring of tumour biomarker levels following treatment can be used to check for recurrence of the cancer.
Different tumour biomarkers are measured in different ways and from different sources. Some markers are found in blood or urine, so these would require you provide a small amount of blood or a urine sample. Other tumour biomarkers such as those involved in faecal occult blood testing (FOBT) can be isolated from faecal matter and require a stool sample. Tissue samples can also contain tumour biomarkers and may involve a tissue biopsy. This is a more invasive procedure than urine or stool sampling. After a doctor takes the sample they are sent to a laboratory for testing using various methods to determine biomarker levels. Particular foods such as red meats or fruits and vegetables can influence the assay and cause false positive results.
Two key factors for an effective tumour biomarker assay are:
The assay must be sensitive in its ability to accurately detect disease; andThe assay must be specific for the particular malignancy.In the early detection or screening of patients for CRC, stool based markers are widely used. Tissue-based markers have been studied as possible prognostic or predictive markers of disease, while CRC biomarkers obtained from serum (blood) are primarily used for the postoperative surveillance of patients.
Tissue based markers
Tissue based markers have been investigated as possible prognostic markers and predictors of response to treatment. Thymidilate synthase (TS) is an enzyme involved in the processing of the cells genetic material and has been studied as a marker that can predict how well a patient may respond to treatment with drugs such as 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine. The transcription factor p53 has also been widely investigated as a biomarker that may predict the severity of cancer how it may respond to particular anticancer drug.
The K-ras oncogene is often associated with cancer as abnormalities in this gene have been found in many tumours. K-ras is involved in sending signals that can regulate how much cells grow or multiply. K-ras mutations are linked to approximately half of all CRCs and have been found to be important in the early stages of the disease. Studies have identified an association between K-ras mutations and poor disease outcome in patients with CRC.
Stool based markers
Faecal occult blood testing (FOBT) is the most commonly used screening test for CRC. There are two main types of FOBT, the guaiac test and the immunochemical test. Both tests detect proteins that may be indicators of colorectal cancer.
The advantages of FOBT for CRC are that the tests are simple and affordable, non-invasive, require very little patient preparation and have the capability of examining the entire colorectal tract. They do however have relatively low specificity and sensitivity for both benign (or precancerous adenomas) and malignant CRC.
Faecal DNA tests are used in screening for CRC on the basis that abnormal DNA is excreted in cells shed from cancerous colorectal lesions. Tests usually use a panel of DNA markers in order to identify mutant genes. DNA markers can provide a more accurate test than FOBT and there are no restrictions on diet or medication. The test is however quite laborious, expensive, also lacks specificity. Examples of stool based DNA markers include K-ras, APC (adenomatous polyposis coli) and p53.
Serum based markers
Serum-based markers of colorectal cancer are mainly used for monitoring patients following the surgical removal of malignant tumours. Patients are monitored regularly following surgery in order to detect any cancer recurrences or metastases. As up to 50% of patients develop recurrent disease or metastases following surgery, this is an important part of CRC management. CEA (carcinoembyonic antigen) was the first serum marker used in patients with CRC, and although it's the oldest, it still remains the most widely used. CEA is mainly used to monitor patients following surgery for primary CRC. A number of studies have shown that intensive monitoring after cancer surgery is associated with an improved outcome if regular CEA measurements were taken. Other serum-based tumour biomarkers used for CRC include markers called CA-19-9, TPA, TPS and TIMP-1
There are three main types of the mammalian ras genes: K-, H- and N-ras. Each of the ras genes makes proteins that are involved in relaying signals between different regions of the cell. These signals play important roles in a number of important biological functions including cell division and cell growth. As mentioned above, the K-ras oncogene is one of the most frequently altered in human cancers, with approximately 50% of CRCs containing mutant K-ras.
While many early investigations suggested that K-ras abnormalities were strong signs of serious disease and poor outcome for patients, more recent studies have found that this may not be correct in all cases. This meant that K-ras might not be very suitable as a prognostic marker.
While there is little evidence that K-ras mutations can be used as an effective screening tool or indicator of prognosis for CRC patients, recent research shows that the gene as a potential marker for prediction of response to specific therapies. Studies have shown that cases of CRC that are associated with mutations in K-ras will not respond well to particular treatments. For example, it has been shown that anticancer drugs such as panitumumab and cetuxamib are not effective in patients with K-ras abnormalities. While these studies do not specifically identify which therapies should be used in the treatment of K-ras associated CRC, they are able to help in the selection of an appropriate therapy.
Tumour Markers: Questions and Answers [online]. 2006 [cited 01/05/08]. Available from: http://www.cancer.gov/cancertopics/factsheet/Detection/tumor-markersDuffy MJ, van Dalen A, Haglund C, Hansson L, Holinski-Feder E, Klapdor R, Lamerz R, Peltomaki P, Sturgeon C, Topolcan O. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. European Journal of Cancer. 2007;43:1348-1360.Duffy MJ, van Dalen A, Haglund C, Hansson L, Klapdor R, Lamerz R, Nilsson O, Sturgeon C, Topolcan O. European Journal of Cancer. Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. 2003;39:718-727.Hassan C, Laghi A, Zullo A, Iafrate F, Morini S. Q&A on diagnosis, screening and follow-up of colorectal neoplasia. Digestive and Liver Disease. 2008;40:85-96.Ehrhardt, A., Ehrhardt, G. R. A., Guo, X., and Schrader, J. W. Ras and relatives—job sharing and networking keep an old family together. Exp. Hematol., 30: 1089 – 1106, 2002.Amado RG. Panitumumab (pmab) afficacy and patient-reported outcomes (PRO) in metastatic colorectal cancer (mCRC) patients (pts) with wild-type (WT) KRAS tumour status. Proceedings of the 2008 Gastrointestinal Cancers Symposium. 2008. ASCO.
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As you may be aware, obesity is associated with a range of health consequences including metabolic diseases (like diabetes), heart disease, some cancers and arthritis. Lifestyle modifications aim to reduce the burden of obesity and reduce the associated conditions. In general, the greater the degree of weight loss achieved, the greater the health benefits. However, even a small amount of weight loss (5-10% of body weight) can lead to significant benefits. Some people consider this small amount of weight loss unsatisfactory, but the health benefits are much more important than physical appearance. You should discuss with your doctor what weight loss aims are suitable for you. 
Most diets produce some weight loss and are successful in the short-term. However, less than 10% of patients will maintain the weight loss in the long term. Once again it must be emphasised that permanent changes to eating habits are required. You must be careful whilst dieting to ensure that you still receive all the essential proteins, vitamins and trace elements. The best way to achieve this is by eating a well balanced diet with a wide variety of nutritious foods. A successful weight loss program may include cutting fats and sugars from your diet while ensuring you eat lots of healthy foods such as wholegrain, fruits and vegetables. Some diet programs may also require you to take vitamin or mineral supplements. 
In addition to reducing your energy intake, increased physical activity is essential for the maintenance of weight loss and should form part of any weight loss program. However, to achieve significant weight loss from exercise alone, a very high level of activity is required, which can be challenging. 
Overall the aim of diet therapies are to reduce caloric intake. There are countless different types of commercial diets available and it is important that you find one that is suited to you and safe. Diets can be broadly categorised into reduced energy, low energy or very low energy diets based on how much they restrict your daily caloric intake. If you are severely obese and have obvious weight related medical conditions, your doctor may suggest a more restrictive very low energy diet for a short period of time. Very low energy diets can produce rapid and marked weight loss by limiting your daily intake with set meal plans, pre-prepared meals or meal replacements. However, following cessation of the program much of this weight will be regained so it is important you try to adhere to other lifestyle changes in the long term. You may also need other treatments such as drugs and behavioural therapy to help you maintain the weight loss. For this reason less restrictive diets are sometimes preferred as you have more freedom and must learn how to select and prepare healthy meal options. The long-term outcomes of the different diets are therefore quite similar.
Behaviour modification methods (such as Cognitive Behavioural Therapy (CBT)) can help improve treatment compliance and improve long-term weight loss. These treatments analyse your behaviours and habits that contribute to poor eating and lack of physical activity. You are encouraged to take responsibility for your weight loss and lifestyle changes. However, these methods however can be very time consuming and expensive.
Surgical treatments tend to be considered if you are morbidly obese (defined as a BMI greater than 40). You must however consider the operative risks associated with each of the procedures. In most cases however, the benefits to your mental and physical health and appearance will outweigh the risks of surgery. If you are markedly obese with co-morbidities, surgery is considered the only available treatment that can reliably produce significant and sustained weight loss. Surgical procedures may help you lose up to 30-40kg of excess weight; however this is only achieved if you adhere to the required lifestyle changes.
CT scans can show several types of tissue with great clarity such as bone, soft tissue and blood vessels and allows easy differentiation between soft tissue structures, which greatly improves on the conventional x-ray. CT scans can detect and determine the exact size and location of anatomical abnormalities such as tumours, lesions, blood clots and blood vessel defects and bone defects. The images produced are generally of cross-sectional nature, with multiple scans creating the ability to produce 3-D images of internal structures. 
A CT scanner consists of a table on which the patient lies which moves in through the ring shaped scanner. A moveable ring located is on the edge of the scanner which contains the x-ray tube and its associated detectors. A CT scan involves the movable ring revolving around the patient with fine fan of x-ray beams being passed through the body from all angles into their associated detectors, with the information from each detector relating to a particular part of the body. All this information from the detectors must be compiled into a detailed image of the particular slice of the body by the computer. Every time the movable ring makes a 360 degree rotation, a slice has been acquired. These slices give such detailed images of the internal structures of the body that they have become widely used in radiology, in both the diagnosis of diseases, checking of bodily structures such as the brain, heart, liver, lungs and kidneys and also in trauma to check for injury. 
Article Date: 14/6/2013 
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