Prof Dr Bernard Weber
A medical doctor and CEO of Laboratoires Réunis, a private medical laboratory based in Luxembourg, Europe. Laboratoires Réunis is a national leader in the field of predictive genetics and molecular diagnosis of infectious diseases and is ISO 15189 accredited since 2006. In the last five years Dr Weber and his team have developed and validated a unique panel of phenotypic and genotypic markers which constitute a very important tool for the integrative approach of multifactorial and environment linked diseases.
Genetic Analysis of Different SNPs as Potential Biomarkers in Colorectal Cancer
Genetic analysis of different SNPs (single nucleotide polymorphisms) as potential prognostic biomarkers in CRC (colorectal cancer) – a pilot study -
Laboratoires Réunis, Junglinster, Luxembourg; 2Laboratoire de Recherche sur le Cancer et les Maladies du Sang, Luxembourg
Colorectal cancer (CRC) occurs either in the colon or rectum. It is the third most common cancer and the second leading cause of cancer-related death in Western Europe. The average lifetime risk of developing CRC is about 5%. Any factor leading to increased cell division in the large intestine can potentially increase the probability of developing CRC. Environmental factors such as a diet that is poor in vegetables and rich in fat may promote cell growth. Additionally cigarette smoke, excessive alcohol consumption and inflammatory bowel disorders such as Crohn’s disease and ulcerative colitis are known to cause overgrowth of colon cells. The majority of CRCs are sporadic cases whereas about 25% of the cases have an inherited compound. Mutations in the genes MSH2 and MLH1 account for only one fifth of the inherited cases of CRC. The rest of the individual colorectal cancer risk is probably due to common genetic variants that, individually, do not contribute much to an increased risk of CRC. However the presence of many variants of these SNPs can contribute to the development of the disease. In this case, the risk can be largely reduced by changing the lifestyle.
In the present study, SNPs related to cell gowth and divison were analysed in 100 patients withan advanced CRC. The carcinomas had a histological staining equal or greater than pT1 and were thus belonging to the adenoma-carcinoma or to the carcinoma stage. The control group consisted of 100 patient not carrying a CRC. Genotyping was performed by melting curve analysis on DNA isolated from whole blood-samples.
The analysed SNPs were: p53 (rs1042522), MDM2 (rs2279744), TGFBR1 (rs334348, rs334349, rs1590), TGFBR4 (rs7871490), SMAD7 (rs4464148, rs12953717, rs493927), PROC3 (rs6983267), FLJ (rs3802842), CHR9 (rs719725) and CHR8 (rs7014346).
Our results show that especially polymorphisms related to TGFBR and SMAD7 seem to be promising CRC predispostion markers. Further studies, which focus on sequencing of the complete genes, will elucidate which role spontaneous mutations as well as known and newly discovered polymorphisms play in the development of CRC.
View .pdf of Presentation here!