Risk Factors of Colorectal Cancer in Taiwan-With Special Reference to the Association With Nutrition, Diet, Obesity, Diabetes Mellitus, and Genetic Alterations
This is a two-year hospital-based case control study. In the fist year, we will set up solid
database of our laboratory regarding the molecular genetics of colorectal cancer. We will
explore the genetic (including APC, k-ras, p53, MSI, etc.) and environmental (including
family history, life style, diet, nutritional status, DM, serum IGF-I, IGFBP-3, etc.) risk
factors of colorectal tumorigenesis. During the whole 2-year period of this project, we will
accrue approximately 1000 patients as experimental group. The control group consists of 2000
individuals who were confirmed without colorectal cancer or polyps by colonoscopy. We
estimated the statistical power of this study will reach more than 90%. In the second year,
we will explore the association between various environmental risk factors with the
epigenetic changes of various oncogenes and tumor suppressor genes. It has been well known
that epigenetic changes of various oncogene and tumor suppressor genes was related to the
intrinsic and extrinsic environmental alterations. Firstly, we will study the correlation
between hypermethylation of promoter region of hMLH1 gene with various environmental
factors. Next, we will explore the genetic polymorphisms of promoter of E-cadherin gene. It
has been well known that E-cadherin plays a major role in the maintenance of cellular
structure. Recently, it has been reported that the C→A genetic polymorphism in the promoter
region of E-cadherin gene in prostate cancer. The experimental method was feasible in our
laboratory. Since this phenomenon has not been reported in colorectal cancer, it is
mandatory for us to extend our research to the E-cadherin polymorphisms of colorectal
cancer. Moreover, this project will focus on exploration of the association between the
genetic polymorphisms of promoter of TS gene with chemosensitivity to 5-Fu-based therapy.
Recent reports indicated that colorectal tumors with MSI have better prognosis. Moreover,
some authors indicated that the genetic polymorphisms of TS genes was related to
chemosensitivity. Therefore, we speculated that the better prognosis in colorectal tumors
with MSI is related to their expression of TS gene. In summary, the second year of this
project will extend our accumulated experience in the study of genetic polymorphisms to
further clarify the association between genetic polymorphisms of TS gene with the prognosis
of colorectal cancers after chemotherapy. We believe that this project will facilitate: (1)
the further clarification of colorectal cancer tumorigenesis; (2) the establishment of
domestic epidemiological data of colorectal cancer of Taiwan, and (3) the improvement of the
quality of clinical management of patients with colorectal cancer.
Observational
Observational Model: Case Control, Primary Purpose: Screening, Time Perspective: Longitudinal, Time Perspective: Prospective
Jin-Tung Liang, M.D., Ph.D.
Principal Investigator
Department of Surgery, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei, TAIWAN, R.O.C.
Taiwan: Department of Health
9361701298
NCT00172757
January 2002
June 2005
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