Press and Public Relations

Blood Clotting and Bowel Cancer Risk

No. 30 | 06/06/2011 | by (Koh)

People whose blood clots more easily than normal are more often affected by cancer. Scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have discovered that a number of variants of clotting factor genes have an influence on bowel cancer risk. They found out that carriers of a particular gene variant of clotting factor V have a bowel cancer risk that is six times higher than people who do not have this gene variant. This study is an important basis for finding out whether and for whom drugs which affect blood clotting may be useful to prevent bowel cancer.

© dkfz.de

Back in the mid 19th century, a French doctor, Armand Trousseau, discovered a connection between cancer and thrombosis – the formation of often dangerous blood clots that can lead to venous occlusion. Today it is known that cancer and its treatment change blood flow properties and thus promote the formation of clots. However, clots do not only occur as a side effect and consequence of cancer, but, vice versa, an increased blood clotting tendency may also be associated with an elevated cancer risk.

About twelve different blood proteins called clotting factors interact in a coordinated manner in the blood clotting (coagulation) process. In the same way as hemophilia (decreased blood clotting) is inherited, genes also play a role in an increased clotting tendency (thrombophilia): There are well studied gene variants (polymorphisms) of a number of clotting factors which are associated with an increased or decreased clotting tendency. Between two and five percent of the population carry such genetic variants.

At the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg, scientists headed by Professor Dr. Hermann Brenner have been studying six gene variants of different clotting factors for a possible connection with colorectal cancer risk. In a large study, they analyzed the occurrence of these six variants in approximately 1.800 colorectal cancer patients and in the same number of healthy control persons.

The team found the most obvious connection for a variant that substantially increases the risk of thrombosis and which is known as factor V Leiden (FVL). Study participants who carry this genetic variant on both copies of their chromosome 1 were found to have a six fold increase in colorectal cancer risk compared to participants who carry two copies of the “standard variant” of factor V. If only one copy of chromosome 1 had the FVL variant, bowel cancer risk was not elevated.

Another connection with bowel cancer prevalence was found by the research team for a particular gene variant of clotting factor XIII: People with this mutation are slightly more rarely affected by venous thrombosis than those who carry the factor XIII standard version. Now the DKFZ team has shown that their colorectal cancer risk is also 15 percent lower. For the other four gene variants studied the team found no connection with bowel cancer risk.

It is known today that coagulation and carcinogenesis are associated. Thus, the interplay of all coagulation (clotting) factors leads to the formation of active thrombin, which, in turn, activates hemostatic fibrin. However, thrombin also contributes to the formation of new blood vessels and is able to dissolve the extracellular matrix, which is the adhesive that keeps cells together. Thrombin may thus make it easier for cancer cells to invade surrounding tissue.

“It is interesting that not every gene variant that increases the tendency to clot automatically also increases the risk of developing colorectal cancer. It also makes a difference whether the gene variant is present on both chromosomes or just on one of them. We therefore have to analyze in detail which clotting factors affect cancer risk and in what manner,” explained study head Hermann Brenner. The knowledge of these connections is the first prerequisite for finding out whether and for whom drugs that affect blood clotting may prevent bowel cancer.

Carla Y. Vossen, Michael Hoffmeister, Jenny C. Chang-Claude, Frits R. Rosendaal, and Hermann Brenner: Clotting Factor Gene Polymorphisms and Colorectal Cancer Risk. Journal of Clinical Oncology 2011, DOI: 10.1200/JCO.2010.31.8873

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

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