Prostate cancer remains the most common tumor in men
Prostate cancer is still the most common tumor disease in men in Germany, more than 60,000 new cases are recorded every year, with the risk for older men being particularly high: “Prostate cancer is typically considered to be a disease of older men. Nevertheless, about two percent of those affected are less than 50 years old when diagnosed, ”according to a current press release from the University Hospital Eppendorf (UKE).
Researchers find an explanation for early infection
But why do relatively young men get prostate cancer again and again? Researchers at the UKE, together with colleagues from the European Molecular Biology Laboratory (EMBL) in Heidelberg, the German Cancer Research Center in Heidelberg and the Max Planck Institute in Berlin, have now found an explanation for this and published it in the journal "Cancer Cell": Few genetic changes are responsible for the development and growth of a tumor - the longer a tumor proliferates, the more mutations are caused by genetic instability.
The number of changes at the beginning of the disease is still relatively small: Because while there are thousands of mutations in advanced tumors, about 40 genetic changes would appear in the early stage of prostate cancer, one of which is responsible for the development of the cancer.
Tumor formation through gene fusion
The researchers also obtained further interesting insights from the investigation of structural changes in the DNA of prostate cancer patients: The DNA was, however, completely but completely mixed up, which would result in breaks and reading errors: "There are only tiny breaks in the genome that the cells are susceptible to make for cancer ", explains Prof. Dr. Thorsten Schlomm, chief physician of the Martini-Klinik, the prostate cancer center at the University Medical Center Hamburg-Eppendorf and main author of the study. This would affect, for example, chromosome 21: Because here the gene" TMPRSS2 "is located on the one hand , which is activated by the male sex hormone testosterone, and the gene “ERG”, which is usually only active in embryos and regulates the development of the organs.
If the distance between the two genes were to break away and the testosterone-dependent gene merges with the embryonic gene, this could result in a tumor - because in the case of a gene fusion, whenever the testosterone acts on the cell, the embryonic gene would also be read, so Dr. Joachim Weischenfeldt from EMBL and co-author of the published study. Such gene mergers can always occur when the cell tries to repair genetic defects, says Dr. Weischenfeldt continues.
Comparison of younger and older patients brings new insights These results are not entirely new - it has been known since 2005 that such gene mergers are linked to the development of prostate cancer. But the research by Prof. Thorsten Schlomm and his colleagues also brought new insights to light: “We have discovered how gene fusions of genes that are dependent on male sex hormones, the androgens, especially promote cancer development in young men, and we have also discovered new gene mergers. In the end, they lead to the cell being damaged and becoming more susceptible to further mutations that then lead to the tumor, "according to the doctor. Because when 90% of the tumors in particularly young patients were compared to those in older patients, the genetic makeup of the cell had Younger men were shown to have hormone-dependent gene fusions, but only 30 percent of the elderly: "In contrast to cancer, the tumors in older patients are caused by an accumulation of genetic errors over time," explains Dr. Weischenfeld.
These differences were then confirmed in a study of more than 10,000 patients operated on in the Martini clinic. "This is the first time that we have proven that there are age-dependent mechanisms of development in the case of frequent cancer," said Dr. Weischenfeldt continues.
Study raises hope of developing preventive measures
The results of the study arouse great hope for the future among the experts: "We hope that our findings will promote the development of new strategies for diagnosis and individualized therapy," said Prof. Schlomm. For example, it is conceivable to treat patients at high risk for this cancer with drugs that reduce the effects of testosterone in the cells.
"Furthermore, we assume that the new understanding of the causes of prostate cancer will now, for the first time, offer the chance to develop effective preventive measures so that the disease cannot develop at all," says the doctor - because that's how it is today it is already possible to detect a genetic change in the blood, but a standardized test would still be missing, which is in preparation, but could be available in three to five years at the earliest.
Prostate cancer in the family increases risk
The risk of developing prostate cancer is particularly high for men who are inherited from the disease - that is, family members of two previous generations have already fallen ill, or two other brothers in one line, for example: Here, the risk is many times higher, says Schlomm : "Men from these families are 17 times more likely to have prostate cancer than the general population. Men who have a father, grandfather or brother are two to four times more likely to have it."
Study part of the largest cancer research project in the world
The current study is an essential part of the research work in the context of the world's largest cancer research project, the International Cancer Genome Consortium (ICGC), which is funded by the Federal Ministry of Education and Research (BMBF) with 7.5 million euros.
The aim of the consortium is to decode the genes of the 50 most important cancers and thus to be able to create a catalog with all cancer-specific genetic changes. In the research project started at the beginning of 2011, international doctors and scientists got to the bottom of the genetic basis of early prostate cancer - the German team led by Prof. Thorsten Schlomm had specifically examined prostate cancer of very young patients. (sb)
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