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Genetic Association between Diabetes and Cancer Discovered

In the article “The Cancer-Associated FGFR4-G388R Polymorphism Enhances Pancreatic Insulin Secretion and Modifies the Risk of Diabetes”*, which was published in the current issue of Cell Metabolism, a research group comprised of scientists from the University Hospital in Tübingen, the Cancer Research Institute in Ontario, Canada, the Max Planck Institute of Biochemistry, Martinsried, Harvard Medical School, USA and the University of Kuopio, Finland describe a genetic mutation they discovered that can help elucidate the association between type 2 diabetes and cancer. The translational study demonstrates the importance of the cancer-inducing gene variant FGFR4-G388R for insulin secretion and diabetes risk.

Diabetes and cancer are diseases that affect a large percentage of the world population. Their prevalence is increasing – not only in industrialized countries, but also in the developing regions of the world. Latest figures show that in 2011 there were approximately 366 million people suffering from diabetes, and that in 2008 there were 12.7 million new cases of cancer worldwide. It is known that in individuals with type 2 diabetes there is a heightened incidence of specific types of cancer, such as breast cancer, colon cancer, uterine cancer and liver cancer. Among the possible mechanisms responsible for this in the focus of the researchers is hyperinsulinemia, an elevated concentration of the hormone insulin in the blood **.
Some time ago, the research group led by Professor Axel Ullrich, director of the Department of Molecular Biology at the Max Planck Institute of Biochemistry in Martinsried, showed a correlation between the mutation FGFR4-G388R in the FGF receptor 4 gene and the progression of breast cancer and resistance to therapy. Now, the research team, which includes the Tübingen DZD scientists Professor Norbert Stefan, Heisenberg Professor of Clinical–Experimental Diabetology, and Professor Hans-Ulrich Häring, medical director of the Department of Internal Medicine IV of the University Hospital Tübingen and member of the board of the DZD, have shown that the same mutation that enhances insulin secretion also modifies the risk of diabetes.
“These new insights into the molecular mechanisms of the signaling function of FGFR4 and the effects of this receptor on blood glucose metabolism in humans cannot explain with certainty the complex association between diabetes and cancer. However, as stated in an editorial on this subject***, they represent an example of a successful collaboration between basic scientists and clinicians from the disciplines of oncology and diabetology in order to better understand this important issue and to advance research in this area,” said Stefan. The Tübingen scientists plan to carry out further studies in cooperation with national and international colleagues of the institutions that are already participating and with colleagues within the German Center for Diabetes Research (DZD), which is funded by the Federal Ministry of Education and Research (BMBF).


Titles of the Publications
*The Cancer-Associated FGFR4-G388R Polymorphism Enhances Pancreatic Insulin Secretion and Modifies the Risk of Diabetes
Ezzat S, Zheng L, Florez JC, Stefan N, Mayr T, Hliang MM, Jablonski K, Harden M, Stančáková A, Laakso M, Haring HU, Ullrich A, Asa SL. The Cancer-Associated FGFR4-G388R Polymorphism Enhances Pancreatic Insulin Secretion and Modifies the Risk of Diabetes. Cell Metabolism 2013; 17: 929-940, doi: 10.1016/j.cmet.2013.05.002

 
**Diabetes und Krebsrisiko [Diabetes and Cancer Risk]
Stefan N, Fritsche A, Häring HU. Diabetes and cancer risk. Dtsch Med Wochenschr 2012;137:1003-1006. doi: 10.1055/s-0032-1304928.


***Does a Single Nucleotide Polymorphism in the FGFR Explain the Connection between Diabetes and Cancer?
Gallagher EM, LeRoith D. Does a Single Nucleotide Polymorphism in the FGFR Explain the Connection between Diabetes and Cancer? Cell Metabolism 2013; 17: 808-809, doi: 10.1016/j.cmet.2013.05.006