Colorectal Cancer and Inflammatory Bowel Disease – Gastrointestinal System Example

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"Colorectal Cancer and Inflammatory Bowel Disease"  is an excellent example of a paper on the gastrointestinal system. Colorectal cancer is the third most commonly diagnosed cancer in the world and it affects more people in developed countries (60% of all cases) and two predisposing factors are lifestyle habits and advancing age (beginning at age 50 until 75). The symptoms include rectal bleeding, anemia (due to the bleeding), weight loss, and change in bowel habits. Colorectal cancer affects either the colon (large intestine) or the rectum and may also include the appendix. Cancer in any site mentioned above is genetically the same type of cancer. Biomarkers are a measured characteristic which serves as good indicators of some biological state, function, or condition that links a specific environmental or carcinogenic exposure to an expected health outcome (NIEHS para.

1) and play an important role in studies that identify and understand the correlation between environmental chemicals and subsequent development of chronic human diseases. The biomarkers for colorectal cancer (CRC) serve useful objectives such as identifying at-risk individuals, improved detection of the disease, and monitoring or predicting patient response to therapies (Konda & Bissonnette 95). Specific examples of colorectal cancer (CRC) biomarkers are classified into three general categories which are molecular markers in colon mucosa, morphological/histological markers, and stool-based markers (ibid. ).

Colonic molecular markers include certain genes with somatic mutations in neoplastic tissue samples and also several kinds of proteins. A few examples of these include K-ras, p53, DCC, and DNA ploidy. Two examples of histologic biomarkers are ACF and adenomas (benign tumors found in the epithelial tissues) while stool-based biomarkers include gFOBT, iFOBT, and DNA-based stool tests, among others.   CRC can be hereditary such as the familial adenomatous polyposis or FAP which is an inherited genetic disorder; it begins as benign growths (polyps) in the colon and rectum.

A variant of FAP is the attenuated FAP (AFAP) in which polyp growth is delayed to the mid-50s instead of the teenage years. A type of high-risk CRC is hereditary nonpolyposis colon cancer (HNPCC) or Lynch syndrome, due to a mismatch of MLH1 or MSH2 genes or in rare cases, in the MSH6 or the PMS2 genes. Both FAP and AFAP are caused by APC gene mutations.

A malignant juvenile or pediatric polyposis is detected by mutations in the PTEN, PTCH, and both SMAD4 and SMAD11 genes but only in conjunction with Cowden syndrome.   Prognostic biomarkers are the biological indicators of the likely progression of CRC. Some of these prognostic biomarkers include CEA, TS, DPD, TP, MSI, ERCC1, EGRF, and VEGF (Konda & Bissonnette 98). A study used and identified key genes and pathways in the pathogenesis of CRC using differentially-expressed genes (DEG) with microarray technology (Wang & Zheng para. 1).

The pathways within the protein-to-protein interaction networks had identified some of these key DEGs such as MET, FZD2, CCND1, PRKCB, WNT2, and JUP.   An elevated CEA (carcinoembryonic antigen) predicted a higher risk of tumor recurrence. A patient with a CEA level of 5.0 ng/ml or higher will likely have a relapse after 17 months. Colorectal cancer is the third-most-common malignancy and also happens to be the third leading cause of cancer deaths among both men and women. Despite the increasing use of biomarkers today, colonoscopy or sigmoidoscopy can usually detect localized bowel cancer in most cases (95%), especially CRC located in the distal colon and in the proximal colon.

Predictive biomarkers are tools for encouraging at-risk individuals to undergo CRC screening tests so these can be detected early and preventive measures are undertaken such as lifestyle changes. On the other hand, prognostic biomarkers are useful for predicting the likely CRC progression and at the same time help in monitoring the efficacy of a treatment regimen. Inflammatory Bowel Disease Inflammatory bowel disease is an ailment that affects all or part of the digestive tract manifested by chronic inflammation.

It is a painful and debilitating medical condition that can be life-threatening in some extreme cases. The two most forms of inflammatory bowel disease  (IBD) are Crohn's disease and ulcerative colitis; the former affects the deep tissues anywhere along the digestive tract while the latter affects usually only the innermost lining of the rectum and the colon. Symptoms of Crohn's disease include diarrhea, abdominal pain, stomach cramp, or blood in the stool caused by ulcers, resulting in weight loss from a reduced appetite. The real cause of inflammatory bowel disease has not been determined but a number of predisposing factors include age, ethnicity, family history, location of residence, cigarette smoking, medications (like analgesics), and diet but gender is not considered a factor as both sexes are equally affected.

Diet and stress were previously thought to aggravate factors but medical scientists and researchers have focused their efforts on the human immune system and on hereditary links or family history. The human body is the home to about 100 trillion different microbes some of which are beneficial while others are clearly harmful.

The name given to all these microbes is the microbiome and managing this is called medical ecology. The human stomach is home to many microbes and research efforts are focused on them. Medical researchers have discovered this microbiome has incredible biodiversity as it includes bacteria (as many as 5,000 different species), viruses, and fungi. Any imbalance in this delicate and invisible inner ecosystem can have profound consequences for the person concerned which scientists suspect include disorders not related directly to bacteria such as diabetes or obesity now in epidemic proportions (Zimmer para.

4) because of changes in diet which in turn had caused changes in the human microbiome ecosystem that includes the digestive tract, the mouth, the urinary tract, lungs, and in the female reproductive organs. An observation of a change in this microbiome which is suspected to contribute to inflammatory bowel diseases (IBD) is the predominance of the bad bacteria which may, in turn, cause the inflammation reaction. This shift in the delicate balance between good and bad bacteria happens when the bad bacteria become too numerous, it triggers the body's immune system by using invariant natural killer T-cells.

In this complex physiological process, these immune cells cause hyper inflammation when there is a disturbance between the immune system and the commensal bacterial flora in the gut (Glocker & Grimbacher 42). However, the exact mechanism of this complex biological reaction is still poorly understood; a hygiene hypothesis and its association with decreased microbial exposure (such as H. pylori bacteria) in childhood probably play a role in the development of IBD in adults (Koloski et al. 165).

It may partly explain why antibiotics can ironically work instead of IBD manifestation because the immune cells now attack healthy cells and thereby causing the inflammation. Probiotics have been used for quite some time to achieve a re-balancing of the stomach microbiome. Probiotics are the live bacteria found in milk and most dairy products like cheese and yogurt but these have limited beneficial effects because most of the bacteria are killed by body heat and stomach acids. However, a new approach is that of using prebiotics which actually plants fibers to be eaten in order to nourish the stomach microbiome by acting as a sort of fertilizer for good bacteria.

Prebiotics increases the intestinal population of beneficial, protective commensal bacteria (Cohen 136). A study tried intestinal homeostasis by using Paneth cell (PC) defensins, which is an innate antimicrobial peptide (Salzman 402). Related to this is how FAP patients who had ileal pouch anastomosis never have problems with IBD but patients already with IBD suffer recurrences. Changes in nucleotide oligomerization domains (NOD) in laboratory mice can confer genetic risks of IBD due to altered gut microbiota.

There is now a higher risk of IDB due to alleles within the NOD2/CARD15 gene.

References

Cohen, Russell D. Inflammatory Bowel Disease: Diagnosis and Therapeutics. New York, NY, USA: Springer Books, 2011. Print.

Glocker, E., and B. Grimbacher. “Inflammatory Bowel Disease: Is it a Primary Immunodeficiency?” Cellular and Molecular Life Sciences 69.1 (2012): 41-48. Web.

Koloski, Natasha, A., Laurel Bret, and Graham Radford-Smith. Hygiene Hypothesis in Inflammatory Bowel Disease: A Critical Review of the Literature. World Journal of Gastroenterology 14.2 (14 Jan. 2008): 165-173. Print.

Konda, Vani, and Marc Bissonnette. “Biomarkers in Colorectal Cancer.” Early Detection and Prevention of Colorectal Cancer. Ed. Karen E. Kim. Thorofare, NJ, USA: SLACK Incorporated, 2009. Print.

National Institute of Environmental Health Sciences (NIEHS). Biomarkers. National Institutes of Health, 11 June 2013. Web. 09 Feb. 2014. .

Salzman, N. H. “Paneth cell defensins and the Regulation of the Microbiome: Detente at the Mucosal Surfaces.” Gut Microbes 1.6 (Nov.-Dec. 2010): 401-406. Web.

Wang, Y. and T. Zheng. “Screening of Hub Genes and Pathways in Colorectal Cancer with Microarray Technology.” Pathology Oncology Research. 07 Feb. 2014. Web. 10 Feb. 2014. .

Zimmer, Carl. “Tending the Body's Microbial Garden.” The New York Times, 18 June 2012. Web. 09 Feb. 2014. .

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