Method for the Prediction of the Risk Potential for Cancerous Diseases and Inflammatory Intestinal Diseases and Corresponding Tests

a cancerous disease and risk potential technology, applied in the direction of biochemistry apparatus, peptide sources, transferases, etc., can solve the problems of difficult to find statistically confirmed associations, complex human metabolism, and clearly adverse metabolic consequences, so as to improve the early detection

US20080107604A1Inactive Publication Date: 2008-05-08MANNS MICHAEL +1
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Patent Information

Authority / Receiving Office
US · United States
Patent Type
Applications(United States)
Current Assignee / Owner
Publication Date
2008-05-08
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention relates to a method for the prediction of the risk potential and / or diagnosis of cancerous diseases or inflammatory intestinal diseases, whereby a DNA sample is tested for the presence of polymorphic UGT1A7 allele. A positive result for a mutation is a positive indication of a sensitivity to cancerous diseases. A prediction of sensitivity to an inflammatory intestinal disease can similarly be made. A PCR amplification of the exon 1, by means of the DNA sample with subsequent sequence analysis is carried out in the method and the determined sequence compared with that of the wild type and the polymorphic allele. The presence or lack of mutations is monitored by means of sequencing the corresponding cDNA using automated fluorescent dye sequencing. The test arrangement for said method requires genetic detection reagents, namely the required primer or cDNAs, on a stationary support in a pre-prepared arrangement or sequence for reading off the results. The recombinant UGT1A7 enzymes are also used for therapeutic purposes.
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Description

FIELD OF THE INVENTION

[0001] The invention relates to a method for predicting the potential risk of carcinomas and inflammatory bowel diseases and for diagnosing these disorders. The invention primarily relates to a method for estimating the potential risk of colorectal carcinomas. The invention further relates to diagnostic tests on DNA samples from an individual to be investigated, and to the use of new polymorphic forms of the UGT1A7 gene for the metabolic characterization of medicaments, especially of tumor therapeutic agents. BACKGROUND OF THE INVENTION

[0002] The current assumption is that the risk of cancer is determined by a genetic predisposition and by environmental effects including exposure to carcinogenic substances.

[0003] It has therefore frequently been assumed that there is an association between genetic polymorphisms of carcinogen-metabolizing enzymes and the development of a cancer. However, specific, statistically confirmed associations are difficult to find bec...

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Embodiment Construction

[0060]FIG. 1 shows a UGT1A7 polymorphism diagnostic method in which the region around the identified polymorphisms is amplified by polymerase chain reaction (PCR). Specific primer pairs which bind about 50 base pairs upstream and downstream of codon 11, of codon 129 / 131 and of codon 208 are used for this. This PCR generates complementary deoxyribonucleic acid fragments (cDNAs) which are 100 to 150 bp in size and which correspond to the wild-type allele or carry the identified polymorphisms.

[0061]FIG. 2 shows the analysis of the prevalence of the polymorphic UGT1A7 alleles as defined in FIG. 3. This analysis, which is based on the defined polymorphic UGT1A7 alleles, shows a, significant association of UGT1A7*4 (SEQ ID NO: 21) and UGT1A7*2 (SEQ ID NO: 19) with colorectal cancer (CRC) and the low occurrence of these alleles in the normal control group (NC). In contrast thereto, inflammatory bowel diseases (IBD) are associated only with the presence of UGT1A7*4 (SEQ ID NO: 21). No sign...