Project: Multi-platform Colorectal Cancer Genetic Testing Portfolio

Colorectal cancer, also called colon cancer or bowel cancer, includes cancerous growths in the colon, rectum or appendix. Colorectal cancer is the third most common form of cancer and it is estimated to cause 655,000 deaths worldwide per year. It is proposed that the prevalence of this disease will increase as the lifetime of man will increase. Colon cancer accounts 10 % of all cancers diagnosed and colon cancer accounts also 10 % in the cancer mortality. In Estonia approximately 700 new colorectal cancer cases will be diagnosed every year and 400 people will succumb due to the disease._x000D_Colorectal cancer is a disease originating from the epithelial cells lining the gastrointestinal tract and typically polyps (adenomas) that can be easily removed precede the actual cancer. Unfortunately colorectal cancer develops mostly without symptoms and the treatment options are limited for the time of diagnosis._x000D_Colorectal cancer can be divided to sporadic and syndromic (hereditary) form and the latter accounts 5-10% of all colorectal cancer cases. Mutations of KRAS; PIK3CA; BRAF; CTNNB1; P53; and other classical cancer related genes have been found to associate with the risk, treatment outcome and life expectancy of the colorectal cancer patients. In the Finnish population CHEK2 gene founder mutations have been identified that is also associated to prostate and other types of cancer. _x000D__x000D_There are 4 subtypes of hereditary colon cancers: Familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, autosomal recessive form of familial adenomatous polyposis and oligodontia-colorectal cancer syndrome._x000D_FAP is caused by the mutations in APC (tumor suppressor gene that is also mutated in the other types of colorectal cancers) or MUTYH gene. The increased risk of Lynch syndrome is due to inherited mutations that degrade the self-repair capability of DNA. Among these genes there are MSH2; MLH1; PMS1; PMS2; MSH6; TFGBR2; MLH3. It is known that 90% of HNPCC are caused by mutations in MSH2 or MLH1 gene. Mutations in the MUTYH gene cause an autosomal recessive form of familial adenomatous polyposis (also called MUTYH-associated polyposis). Fourth heritable colorectal cancer syndrome is called „oligodontia-colorectal cancer syndrome”, that is caused by mutations that lead to transcription termination of the AXIN2 gene._x000D__x000D_During the recent years there has been substantial increase in the knowledge of genetic background, treatment options and epidemiology of colorectal cancer. Number of articles has been published showing the association of specific DNA markers with the increased or decreased risk of colorectal cancer during the lifetime. _x000D__x000D_The aim of the current project is to summarize this knowledge and develop full portfolio of genetic tests for the majority of hereditary and sporadic colorectal cancers. The biggest effort will be placed on the analysis and interpretation of the tests, to give the answer to the questions important for the doctors, patients and their relatives as well. One application of the test would be the genetic screening for people who have had close relatives with colorectal cancer previously diagnosed. If the genetic predisposition of colorectal cancer will be identified the suggestions for the more frequent health control, specific diet or in some cases even preventive surgery can be suggested. As prior the development of the colorectal cancer typically the polyps occur, the biopsy sample analysis would be highly informative to assess the malignancy level and choose the best treatment method and drug doses if necessary. _x000D_Within this project the biologically and clinically relevant questions will be defined by the clinicians of colorectal cancer together with molecular biologists. Statistically significant genes and molecular markers will be selected and validated according to latest publications. Most suitable technological platform for the DNA analysis as well as techniques for sample collection, storage and preparation will be selected. In the final step the tests will be validated and introduced to the market together with interpretation and genetic consultation._x000D_As a result of the project new diagnostic and prognostic tools for the doctors and citizens will be available. These applications will help the doctors to subclassify the colorectal cancer, assess the malignancy level of the polyps that can potentially transform to cancers, select the appropriate treatment options and therapy intensity, more precisely predict the survival. As a by-product of these tests new potential drug targets may emerge. The most important benefit of these tools lies in early detection and diagnosis that leads to better survival and treatment outcome as well as decrease of funds for the treatment of the disease._x000D__x000D_

Acronym MCCGTP (Reference Number: 4292)
Duration 01/05/2009 - 30/04/2012
Project Topic The aim of the project is to develope the portfolio of genetic tests for the detection and risk assessment of sporadic and hereditary colorectal cancers based on the literature. Integration of the genetic and clinical data will be implemented.
Project Results
(after finalisation)
Development of prototype tests for genetic testing of colorectal cancer, which could predict disease risks and survival, as well as specify diagnosis and choose better treatment strategies. _x000D_
Network Eurostars
Call Eurostars Cut-Off 1

Project partner

Number Name Role Country
3 Asper Biotech Ltd. Coordinator Estonia