Epidemiological evidence from numerous studies show that neuropsychiatric or central nervous system (CNS) disorders may protect against cancer. For example, patients with alzheimer’s disease, parkinson and schizophrenia have a lower than expected probability of developing some types of cancer. One of the most remarkable example is alzheimer’s disease. The available data suggest that patients with alzheimer’s disease have a reduced the risk – up to 50% less – of suffering from cancer. Various theories have been put forward in an attempt to explain this relationship between diseases that, at a first glance, seem to be so different from the pharmacological, genetic and environmental perspectives. However, the available results were not consistent enough to confirm these models.[1]
Alfonso Valencia, a researcher and Vicedirector of Basic Research at Centro Nacional de Investigaciones Oncologicas (CNIO), in Madrid, Spain and his team, today publishes the first real evidence of a molecular relationship between cancer and central nervous system diseases in the journal PLOS Genetics. The study, conducted in collaboration with the psychiatrist Rafael Tabar?s-Seisdedos from the University of Valencia and the Center for Biomedical Research in Mental Health (CIBERSAM), and the computational biologist Ana?s Baudot, from the CNRS in Marseille, France, identifies almost a hundred genes which could explain this relationship.[2]
… This is the first time that a molecular relationship between these diseases has systematically been found…
Inverse comorbidity
“We had previously published that several diseases of the brain and nervous system, particularly those which have a neurodegenerative component, are associated with a lower risk of cancer. We refer to this epidemiological evidence as inverse comorbidity,” explained Valencia, and added: “In spite of the evidence, we did not have the molecular details which could explain this protective effect, in other words, which genes could be behind this behavior.”
Paradoxical relationship
To look further into this paradoxical relationship, the authors of the study used bioinformatic analysis to compare data on the genetic expression of nearly 1,700 people from over 30 studies on diseases in the central nervous system (alzheimer, parkinson and schizophrenia) and cancer (colon, lung and prostate cancer).
Gene Signature
The results show that almost a hundred genes could be behind the relationship between these diseases: 74 genes which were less active in nervous system diseases were found to be more active in cancer; on the other hand, 19 genes which were more active in nervous system diseases were found to be less active in cancer.
“It is precisely these genes which are inversely activated which could explain the lower risk of cancer in patients with nervous system diseases,” said the authors of the study. C?sar Boullosa and Kristina Ib??ez, predoctoral researchers in Valencia’s lab, highlighted that “up to 90% of biological processes which appear a greater presence in cancer have a reduced presence in the nervous system diseases analysed.”
This data demonstrates that the “global regulation of cell activity could have a protective effect from diseases with inverse comorbidity,” concluded the article. “At the beginning of the project we did not really expect to get statistically significant results, so it was it came as a great surprise to find a clear genetic correlation between these two types of disease,” Valencia admitted. He also explained that it is “the first time that a molecular relationship between these diseases has systematically been found.”
Genetic association
Among the genes identified in the study is PIN1, previously found to be related to both Alzheimer’s disease and cancer, as well as genes involved in p53 and Wnt signalling pathways. The study has also identified genes related to crucial biological processes for life such as cell metabolism and communication between cells and their external environment.
The researchers propose that this genetic association amongst illnesses could open the door to the use of antineoplastic drugs to treat some nervous system diseases, as well as the other way round. One example of this practice is bexarotene (Targretin?; Medicis, a division of Valeant Pharmaceuticals), an antineoplastic agent that has already displayed beneficial effects for treating Alzheimer’s Disease in mice. The study represents an example of the new possibilities genomics and bioinformatics can offer in a comprehensive approach to complex diseases such as cancer or nervous system disorders.
For more information:
[1] Ib??ez K, C?sar Boullosa C, Tabar?s-Seisdedos R, Baudot A, Valencia A. Molecular Evidence for the Inverse Comorbidity between Central Nervous System Disorders and Cancers Detected by Transcriptomic Meta-analyses. PLOS Genetics. February 20, 2014DOI: 10.1371/journal.pgen.1004173 [Article]
[2]Tabar?s-Seisdedos R, Dumont N, Baudot A, Valderas JM, Climent J, Valencia A, et al. No paradox, no progress: inverse cancer comorbidity in people with other complex diseases.Lancet Oncol. 2011 Jun;12(6):604-8. doi: 10.1016/S1470-2045(11)70041-9. Epub 2011 Apr 15.[Article][PubMed]
Photo: Alfonso Valencia, a researcher at the Centro Nacional de Investigaciones Oncologicas (CNIO) in Madrid, Spain. Photo Courtesy: CNIO, Mardrid, Spain.
Copyright ? 2014 InPress Media Group/Sunvalley Communication. All rights reserved. Republication or redistribution of InPress Media Group/Sunvalley Communication content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group/Sunvalley Communication. InPress Media Group/Sunvalley Communication shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Onco’Zine and Oncozine are registered trademarks and trademarks of Sunvalley Communication around the world.
