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If a father or brother has prostate cancer, his son or brother has an increased risk of this type of cancer. Whether this also applies when precancerous stages of this cancer are discovered in relatives has not yet been known. Now scientists have analyzed data from more than six million men to find out how high the risk of prostate cancer is in this case. Researchers at the German Cancer Research Center (DKFZ) and the National Center for Tumor Diseases (NCT) in Heidelberg have been able to show that the risk of prostate cancer is similarly increased in relatives of patients with precursors. This should be taken into account in consultations on early detection.

The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center (DKFZ), the University Hospital Heidelberg (UKHD) and the German Cancer Aid (DKH).

Prostate cancer is now the most common malignancy in men in Germany and accounts for about 20 percent of all new cancer cases in men. Ten percent of all cancer deaths in men are caused by prostate carcinoma - it is the third most frequent cause of cancer death after lung and colon cancer. Worldwide, prostate cancer is the second most common type of cancer in men and the fifth most frequent cause of cancer death. More than 58,000 men are diagnosed with this cancer every year in Germany, and more than 14,000 men annually die of it.

The causes of prostate cancer are still poorly understood. An important risk factor is age: 90 percent of all patients are older than 60 years; it is rarely observed in people under 45 years of age. According to several studies, however, the strongest risk factor seems to be family history. Invasive prostate carcinomas are the strongest risk factor for family members to develop prostate carcinoma themselves. Whether certain precursors of prostate cancer - so-called borderline prostate neoplasia (e.g. atypical small acinar proliferation, ASAP) or prostate carcinomas in situ (e.g. prostate intraepithelial neoplasia, PIN) - also increase this risk in the family history has now been investigated for the first time in a large study carried out by scientists from Heidelberg.

"This is the world's largest cohort study on familial prostate cancer," said Mahdi Fallah, head of the Risk Adapted Prevention Group in the Department of Preventive Oncology at the DKFZ and the NCT Heidelberg. In cooperation with colleagues from the University of Lund, the Heidelberg researchers have analyzed the data of 6.3 million Swedish men born after 1931 and their parents. During the study period from 1958 to 2015, 238,196 men (3.8 percent) developed invasive prostate cancer and 5,756 men (0.09 per cent) developed one of the precursors of prostate cancer investigated.

"Our analyses of this largest database of its kind in the world showed that if first-degree relatives - i.e. father or brother - have a precursor stage of prostate cancer, men are 1.7 times more likely to develop invasive prostate cancer themselves compared to men without prostate cancer or precancerous stages in their family history," Mahdi Fallah reports. This increased risk of prostate cancer is close to that of men who have relatives with invasive prostate cancer: They have about 2-fold higher risk.

In addition, men who have a first-degree prostate cancer precursor in a first-degree relative have 1.7 times the risk of dying of invasive prostate cancer - also compared to men who have no relatives with prostate cancer precursors or prostate cancer. The risk of prostate cancer is 2-fold in men whose relatives have been diagnosed with precancerous lesions under the age of 60, which is slightly higher than that in men whose relatives have been diagnosed with precancerous lesions at an older age (1.7 times).

"If there are precursors of prostate cancer in the family history, these tumor forms are therefore just as relevant as invasive forms of prostate cancer in relatives - in terms of both the incidence of prostate cancer and mortality," explains Mahdi Fallah.

"Since family history is the strongest known risk factor for prostate cancer, these study results also have an impact on prevention - namely on the risk-adapted early detection of prostate cancer," adds Elham Kharazmi, co-leader of the study and scientist at the DKFZ and the NCT Heidelberg. Not only prostate cancer, but also precursors of it in the family history should be included in the consultation of family members for early detection and risk assessment.

Original publication:
X. Xu, M. Fallah, Y. Tian, T. Mukama, K. Sundquist, J. Sundquist, H. Brenner, E. Kharazmi: Risk of invasive prostate cancer and prostate cancer death in relatives of patients with prostatic borderline or in situ neoplasia: A nationwide cohort study. Cancer 2020; https://doi.org/10.1002/cncr.33096

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Press contact:
Dr. Friederike Fellenberg
National Center for Tumor Diseases Heidelberg (NCT)
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German Cancer Research Center (DKFZ)
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Heidelberg University Hospital and Medical Faculty of the University of Heidelberg
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National Center for Tumor Diseases Heidelberg (NCT)
The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center, Heidelberg University Hospital (UKHD) and German Cancer Aid. The NCT's goal is to link promising approaches from cancer research with patient care from diagnosis to treatment, aftercare and prevention. This is true for diagnosis and treatment, follow-up care or prevention. The interdisciplinary tumor outpatient clinic is the central element of the NCT. Here, the patients benefit from an individual treatment plan prepared in interdisciplinary expert rounds, so-called tumor boards. Participation in clinical studies provides access to innovative therapies. The NCT thereby acts as a pioneering platform that translates novel research results from the laboratory into clinical practice. The NCT cooperates with self-help groups and supports them in their work. Since 2015, the NCT Heidelberg has maintained a partner site in Dresden. The Hopp Children's Cancer Center (KiTZ) was established in Heidelberg in 2017. The pediatric oncologists at KiTZ work together in parallel structures with the NCT Heidelberg.

German Cancer Research Center (DKFZ)
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.
Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Tumour Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent universtity medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

Heidelberg University Hospital (UKHD)
Heidelberg University Hospital (UKHD) is one of the most important medical centers in Germany; Heidelberg University's Medical Faculty is one of Europe's most prestigious biomedical research facilities. Their shared objective is the development of innovative diagnostics and treatments and their prompt implementation for the benefit of the patient. The hospital and faculty employ approximately 13,000 individuals and are involved in training and qualification. Every year approximately 65,000 patients are treated as inpatients and 56,000 as day patients in more than 50 specialized clinical departments with around 2,000 beds, with more than 1 million patients being treated as outpatients. Together with the German Cancer Research Center and German Cancer Aid, the Heidelberg University Hospital established The National Center for Tumor Diseases (NCT) Heidelberg as the leading oncology center of excellence in Germany. The Heidelberg Curriculum Medicinale (HeiCuMed) is at the forefront of medical training in Germany. At present 3,700 aspiring physicians and doctors are studying in Heidelberg.