ORIGINAL ARTICLE ROLE OF PHYTOCHEMICALS (DIET) IN CHEMOPREVENTION OF FAMILIAL ADENOMATOUS POLYPOSIS

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1 ROLE OF PHYTOCHEMICALS (DIET) IN CHEMOPREVENTION OF FAMILIAL ADENOMATOUS POLYPOSIS R. Karunadevi 1, K. P. S. Adinarayana 2, P. Ajay Babu 3 HOW TO CITE THIS ARTICLE: R. Karunadevi, K. P. S. Adinarayana, P. Ajay Babu. Role of phytochemicals (diet) in chemoprevention of familial adenomatous polyposis. Journal of Evolution of Medical and Dental Sciences 2013; Vol2, Issue 30, July 29; Page: ABSTRACT: Familial Adenomatous Polyposis(FAP) is caused by the mutations of human suppressor APC Gene. Molecular genetic testing confirms the diagnosis, but most of the Indian population cannot use this technology because of limited availability and financial constraints. Clinical findings are also considered for diagnosis of this disease. Once the diagnosis of FAP is done colonoscopic surveillance and polypectomy is done. In severe cases prophylactic colonectomy or partial colonectomy and surveillance of remaining colon is necessary, or it may become malignant. We found taking diet containing ginger (gingerol) and turmeric (curcumin), and avoiding diet containing beta-catenin helps in arresting progress of the disease. However more trials with diet must be undertaken to rely on its benefits. KEY WORDS: - Familial adenomatous polyposis, APC, Beta-Catenin, Curcumin, Gingerol. INTRODUCTION: FAP is an inherent condition in which numerous polyps form in the epithelium of the large intestine. Familial Adenomatous Polyposis is not of frequent occurrence in India, and hence its diagnosis may be missed, thereby the affected person may miss the genetic counseling. The relevant clinical findings and diagnostic techniques are given below. Colonoscopic examination reveals the presence of adenomatous polyps [1,2] anywhere in the colon. Histo-pathological examination reveals the nature of the growth. Ultrasound of abdomen and blood tests evaluate liver function tests, it is necessary to rule out liver metastasis. Gene testing provides the ultimate diagnosis in 95% of cases. Genetic counseling is needed in families where FAP is diagnosed. Defective APC gene (defective copy of a specific gene) testing and sequencing the defective portion of the gene will identify the borderline cases. When working properly, this gene produces a special protein substance that keeps polyps from developing in the colon. When this gene is defective, the protein no longer functions properly and polyps begin to appear. Without treatment colon cancer almost inevitably develops from one or more of these polyps. APC gene is very large and mutation can occur anywhere in the gene, hence detecting APC mutation is very difficult. The most widely available FAP genetic test is protein truncation test or PTT. MATERIALS & METHODS: The colonoscopic register of the gastroenterology department of King George Hospital, Visakhapatnam is analysed from to with 1059 recorded examinations. Pathological reports were also examined whenever necessary. The following members of the same family are taken for detailed study. 1. The oldest member of this family who died of cancer, which was preceded by bleeding per rectum, leaving her only son. Journal of Evolution of Medical and Dental Sciences/ Volume 2/ Issue 30/ July 29, 2013 Page 5615

2 2. This only son also died of cancer preceded by bleeding per rectum on leaving behind his wife, two sons and one daughter. 3. His wife is now aged about 55 years. 4. Eldest son aged 37 years with date of birth Second son aged 34 years with date of birth His youngest daughter aged 30 years with date of birth OBSERVATION: The second son was the first in the family to seek medical advice, with complaints of pain abdomen and streaks of blood in stools. Colonoscopic, histo-pathological and fundus examination of eye, sister chromatid exchanges (SCE), and family history confirmed FAP. He underwent total proctocolectomy with ileoanal anastomosis at the age of 30 years. Three years after the operation he continues to lead a normal life with no complaints at all. Diet may also be a contributing factor. The youngest daughter was the next to seek medical advice with the complaint of bleeding per rectum. Colonoscopic examination, pathological reports, S.C.E. reports confirmed FAP. She was treated with Laparoscopic Proctocolectomy. After 1 year she is found to be leading a normal and active life. Colonoscopy was done to eldest son at the age of 36 years, and multiple polyps were present. He did not undergo operation though multiple polyps were found, after one year again histopathological examination was done and no atypical findings were present. Colonoscopy was done to mother and no polyps were found. She did not have any FAP symptoms. But the family history and clinical findings confirmed it is FAP affected family. DISCUSSIONS: Common FAP Symptoms are pain abdomen, rectal bleeding, and profuse diarrhoea [2] which can result in K + deficiency causing muscle weakness. FAP is an inherited condition in which numerous polyps are formed mainly in the colon. This condition can be diagnosed by the Colonoscopy and Pathological examination. Other extra intestinal manifestations variably present are (1) Congenital Hypertrophy of retinal pigment epithelium [3] (2) Benign cutaneous lesions, (3) Dental abnormalities (4) Osteomas. 5) Soft tissue tumours (6) Polyps in Duodenum and stomach. Sister chromatid exchanges indicate gene toxicity [4, 5]. FAP is caused by the mutation of tumour suppressor gene APC [6]. The average age of onset of this condition varies by mutation location. At codon 1309-Age 20 years [7]. Between codon 168 and 1580 excluding (1309) age 30 years. 5 of codon 168 and 3 of codon 1580 age 52 years. APC protein is involved in degrading the transcriptional co-factor beta catenin [8] and increase in beta catenin [8, 9, 10, 11, 12, 13, 14] production appears to increase the proliferation of tumours. Cancer preventing compounds are known to be present in fruits, vegetables and other plant sources which are used as ingredients of our diet. They may be used to inhibit, reverse or retard tumorigenesis [15]. Curcumin, capsaicin, gingerol, epigallocatechin-3-galleta, genestein, diallyl Journal of Evolution of Medical and Dental Sciences/ Volume 2/ Issue 30/ July 29, 2013 Page 5616

3 sulphide are some of the plant products which are studied for their beneficial effect on human health. Turmeric which contains curcumin, ginger which contains gingerol are used in our diet and we focused on these two in our study. Quantity of ginger and turmeric used are 10 grams per day in three divided doses cooked along with food. These are relatively non-toxic and inexpensive. Omega-3 fatty acids present in fish appear to reduce the levels of beta catenin. Elevated levels of beta catenin are associated with the development of variety of tumours. The eldest son got colonoscopy examination for the first time in 2009 and multiple polyps were found. But he did not undergo colectomy operation. He completely gave up chicken and mutton which are Beta catenin sources [17]. He took only vegetarian diet with more ingredients of turmeric [15] and ginger [15]. After one year he got colonoscopy and there was no further progress of FAP. The pathological examination diagnoses was, Hyperplastic polyps with no atypical features thus indicating that the progress of the disease is arrested. The other FAP affected family members took the same diet. These members are also leading very active and healthy life. DATA FROM COLONOSCPIC REGISTER to Total No. of Examination Multiple Polyposis Polypoidal growth Male Female Male Female Out of 1059 Examinations from the colonoscopic register during the course of 3 years no FAP could be diagnosed. Only recently one family affected by FAP could be examined. The detailed study is given above. The present paper focuses on chemo prevention with phytochemicals[15,19] at the same time avoiding of beta catenin from diet[18] which is associated with the development of tumours which may ultimately turn to be malignant[3]. CONCLUSION: The study report describes the FAP cases over a period of 3 years from KGH, Visakhapatnam, Andhra Pradesh, India. From the above observations, all members of one family who are diagnosed FAP are taken up. The study resulted in few concluded points such as, shifting from non-vegetarian diet to vegetarian diet and elevated levels of ginger and curcumin in vegetarian diet might be one of the reasons for the arrest of FAP disease. This report is based on one family who are diagnosed as FAP; further studies are in progress to include few more families in order to ascertain the importance of ginger and curcumin in vegetarian diet. ACKNOWLEDGMENT: We extend our thanks to the gastroenterology department of Andhra Medical College, Visakhapatnam Andhrapradesh. Journal of Evolution of Medical and Dental Sciences/ Volume 2/ Issue 30/ July 29, 2013 Page 5617

4 REFERENCES: 1. Feron ER, Vogelstein B A Genetic model for colorectal tumorigenesis. Cell, 1990; 61: Cannon-Albright LA, Skolnick MH, Bishop DT, Lee RG, Burt RW Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. N Engl J Med. 1988; 319: Powell SM, Petersen GM, Krush AJ, Booker S, Jen J, Giardiello FM et al Molecular diagnosis of familial adenomatous polyposis. N Engl J Med. 1993; 329: Stetka DG, Wolff S Sister Chromatid Exchange as an assay for genetic damage induced by mutagen-carcinogens. II. In vitro test for compounds requiring metabolic activation. Mutat Res. 1976; 41: Latt SA and Schreck RR Sister Chromatid Exchange analysis. Am J Hum Genet. 1980; 32: Yoshi Y, Nagase H, Ando H, Horii A, Ichii S, Nakatsuru S, et al -Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet. 1992; 1: APC Associated Polyposis conditions Gene reviews NCBI Book shelf. 8. Sieber OM, Segditsas S, Knudsen AL, Zhang J, Luz J, Rowan AJ et al Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation. Gut. 2006; 55: Brett Anthony Hoover Beta-catenin Mediated Wnt Signaling as a Marker for Characterization of Human Bone Marrow-Derived Connective Tissue Progenitor Cells. Journal of young investigators. 2005; 12: Rubinfeld B, Albert I, Porfiri E, Munemitsu S, Polakis P Loss of beta-catenin regulation by the APC tumor suppressor protein correlates with loss of structure due to common somatic mutations of the gene. Cancer Res. 1997; 57: Bullions LC, Levine AJ The role of beta-catenin in cell adhesion, signal transduction, and cancer. Curr Opin Oncol. 1998; 10: Takayama T, Shiozaki H, Shibamoto S, Oka H, Kimura Y, Tamura S, et al Beta-catenin expression in human cancers. Am J Pathol. 1996; 148: Munemitsu S, Albert I, Souza B, Rubinfeld B, and Polakis P Regulation of intracellular betacatenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein. Proc Natl Acad Sci U S A. 1995; 92: Polakis P The adenomatous polyposis coli (APC) tumor suppressor. Biochim Biophys Acta. 1997; 1332: F Surh YJ Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003; 3: Simopoulos AP Omega-3 fatty acids in health and disease. Prog Clin Biol Res. 1990; 326: Lu J, Chuong CM, Widelitz RB Isolation and characterization of chicken beta-catenin. Gene. 1997; 196: Rozen P, Hellerstein SM, Horwitz C The low incidence of colorectal cancer in a "high-risk" population: its correlation with dietary habits. Cancer.1981; 48: Journal of Evolution of Medical and Dental Sciences/ Volume 2/ Issue 30/ July 29, 2013 Page 5618

5 19. Kucuk O New opportunities in chemoprevention research. Cancer Invest. 2002; 20: AUTHORS: 1. R. Karunadevi 2. K.P.S. Adinarayana 3. P. Ajaybabu PARTICULARS OF CONTRIBUTORS: 1. Associate professor, Department of Physiology, NRI institute of Medical Sciences, Visakhapatnam. 2. Associate professor, Department of Anatomy, Andhra Medical College, Visakhapatnam. 3. Head, Biolab, Translational Research Institute of Molecular Sciences (TRIMS) Laboratory, Visakhapatnam. NAME ADRRESS ID OF THE CORRESPONDING AUTHOR: Dr. R. Karunadevi, D/No: , Lalithanagar, Visakhapatanam, Andhrapradesh. Pin karunarednam@yahoomail.com Date of Submission: 20/07/2013. Date of Peer Review: 21/07/2013. Date of Acceptance: 22/07/2013. Date of Publishing: 26/07/2013 Journal of Evolution of Medical and Dental Sciences/ Volume 2/ Issue 30/ July 29, 2013 Page 5619