Maria Blettner

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mayence, Rheinland-Pfalz, Germany

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Publications (405)1419.62 Total impact

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    ABSTRACT: The purpose of this retrospective multicenter study was to resolve the pseudo-paradox that the clinical outcome of women affected by breast cancer has improved during the last 20 years irrespective of whether they were treated in accordance with clinical guidelines or not. This retrospective German multicenter study included 9061 patients with primary breast cancer recruited from 1991 to 2009. We formed subgroups for the time intervals 1991-2000 (TI1) and 2001-2009 (TI2). In these subgroups, the risk of recurrence (RFS) and overall survival (OS) were compared between patients whose treatment was either 100 % guideline-conforming or, respectively, non-guideline-conforming. The clinical outcome of all patients significantly improved in TI2 compared to TI1 [RFS: p < 0.001, HR = 0.57, 95 % CI (0.49-0.67); OS: p < 0.001, HR = 0.76, 95 % (CI 0.66-0.87)]. OS and RFS of guideline non-adherent patients also improved in TI2 compared to TI. Comparing risk profiles, determined by Nottingham Prognostic Score reveals a significant (p = 0.001) enhancement in the time cohort TI2. Furthermore, the percentage of guideline-conforming systemic therapy (endocrine therapy and chemotherapy) significantly increased (p < 0.001) in the time cohort TI2 to TI for the non-adherent group. The general improvement of clinical outcome of patients during the last 20 years is also valid in the subgroup of women who received treatments, which deviated from the guidelines. The shift in risk profiles as well as medical advances are major reasons for this improvement. Nevertheless, patients with 100 % guideline-conforming therapy always had a better outcome compared to patients with guideline non-adherent therapy.
    Breast Cancer Research and Treatment 06/2015; DOI:10.1007/s10549-015-3484-2
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    ABSTRACT: Malperfusion adversely affects outcomes in patients with acute type A aortic dissection, but reliable quantitative data are lacking. The aim of this study was to analyze the impact of various forms of malperfusion on early outcome. A total of 2,137 consecutive patients enrolled in GERAADA (German Registry for Acute Aortic Dissection Type A) who underwent surgery between 2006 and 2010, of whom 717 (33.6%) had any kind of pre-operative malperfusion, were retrospectively analyzed. All-cause 30-day mortality was 16.9% and varied substantially according to the number of organ systems affected by malperfusion (none, 12.6%; 1 system, 21.3%; 2 systems, 30.9%; 3 systems, 43.4%; p < 0.001). Pre-operative cerebral malperfusion, comatose state, peripheral malperfusion, visceral malperfusion, involvement of supra-aortic branches, coronary malperfusion, and renal malperfusion were all independent predictors of developing any post-operative malperfusion syndrome. When survival was considered, age, peripheral malperfusion, involvement of supra-aortic branches, coronary malperfusion, spinal malperfusion, a primary entry in the descending aorta, and pre-operative comatose state were independent predictors, again with increasing significance. Malperfusion remains a severe clinical condition with strong potential for adverse outcomes in patients undergoing surgery for acute type A aortic dissection. The GERAADA registry suggests that the impact of the number of organs involved and the type of malperfusion on outcome differs substantially. Introducing an appropriate classification system, such as "complicated" and uncomplicated" acute type A aortic dissection, might help predict individual risk as well as select a surgical strategy that may quickly resolve malperfusion. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 06/2015; 65(24). DOI:10.1016/j.jacc.2015.04.030
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    Maria Blettner
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    ABSTRACT: Blood viscosity has a role in modulating cardiovascular homeostasis; changes in this parameter have been associated with cardiovascular mortality and morbidity. However, it remains unclear whether these changes are (1) involved in the pathophysiology of disease, (2) an epiphenomenon, or (3) the expression of counterregulatory mechanisms. We report data on the normal values of blood viscosity and its association with cardiovascular risk factors, prevalent cardiovascular disease, and blood pressure in a large population-based cohort study. Viscosity was calculated using validated formulae and its associations were explored in 15,010 participants (mean 55.0, min-max: 35-74 years old; 49.5% women) from the Gutenberg Health Study as well as in a subgroup of 3223 subjects (61.1% women, mean age 49.2, min-max 35-74 years old) without risk factors or self-reported cardiovascular disease. Age- and gender-adjusted mean values for viscosity were defined. Regression models showed a relationship between classical risk factors and blood viscosity measures; the overall R (2) of the multiple linear regression model was however as low as 0.067 and 0.049 for high and low shear stress viscosity, respectively. After correction for cardiovascular risk factors, there was a very mild association between viscosity and prevalent coronary artery disease and heart failure. Systolic, mean and diastolic blood pressure increased with increasing blood viscosity after correction for age and gender. We provide reference values for viscosity in a population-based cohort. Blood viscosity decreases in older subjects and shows a very mild association with cardiovascular risk factors and prevalent disease in our cohort. There is a linear positive association between viscosity and blood pressure. © The Author(s), 2015.
    Therapeutic Advances in Cardiovascular Disease 06/2015; DOI:10.1177/1753944715589887
  • Senologie - Zeitschrift für Mammadiagnostik und -therapie 05/2015; 12(02). DOI:10.1055/s-0035-1550586
  • Senologie - Zeitschrift für Mammadiagnostik und -therapie 05/2015; 12(02). DOI:10.1055/s-0035-1550569
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    ABSTRACT: A previous study on papillary thyroid carcinomas (PTC) in young patients who were exposed to (131)Iodine from the Chernobyl fallout revealed an exclusive gain of chromosomal band 7q11.23 in exposed cases compared to an age-matched control cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially expressed between exposed and non-exposed cases at mRNA and protein level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been developed in a follow-up study. Here we used CLIP2 typing data on 117 post-Chernobyl PTCs from two cohorts of exposed patients with individual dose estimates and 24 non-exposed controls to investigate a possible quantitative dose-response relationship of the CLIP2 marker. The "Genrisk-T" cohort consisted of 45 PTCs and the "UkrAm" cohort of 72 PTCs. Both cohorts differed in mean dose (0.59 Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (2 years Genrisk-T, 8 years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was comparable. We analyzed the association between the binary CLIP2 typing and continuous thyroid dose with logistic regression. A clear positive dose-response relationship was found for young PTC cases (AaO < 20 years, AaE < 5 years). In the elder age group a higher proportion of sporadic tumors is assumed due to an increased frequency of CLIP2 negative cases, suggesting different molecular mechanisms in sporadic and radiation-induced cases. This is further supported by the association of elder patients (AaO > 20 years) with positivity for BRAF V600E mutation. © The Author 2014. Published by Oxford University Press.
    Carcinogenesis 05/2015; DOI:10.1093/carcin/bgv043
  • Breast Care 05/2015; DOI:10.1159/000381933
  • Cancer Research 05/2015; 75(9 Supplement):P3-09-06-P3-09-06. DOI:10.1158/1538-7445.SABCS14-P3-09-06
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    ABSTRACT: Inflammatory breast cancer (IBC) represents a rare and aggressive form of cancer with negative prognosis and high rate of recurrence. The purpose of this retrospective multi-center study was to evaluate the effect of IBC on overall and disease-free survival. Furthermore we analyzed the influence of hormone and Her2 receptor expression on inflammatory breast cancer cells on the clinical outcome of patients. This retrospective German multi-center study included 11,780 patients with primary breast cancer recruited from 1992 to 2008. In this sub-group analysis we focused on 70 patients with IBC. Despite the relatively small sample size, we could confirm the aggressiveness of inflammatory breast cancer and the different clinical behavior of IBC subtypes. It could be demonstrated that the lack of expression of hormone receptors on tumor cells is associated with a more aggressive clinical course and decreased overall and disease-free survival. Higher incidence of Her2 overexpression, that is typically associated with poor prognostic outcome among women with non-IBC tumors, seems however to have no prognostic significance. This BRENDA sub-group analysis, on a German cohort of breast cancer patients confirmed the negative outcome of IBC and the different clinical behavior of IBC subtypes. The best management of IBC requires intensive coordination and cooperation between various clinical disciplines involved in the treatment of IBC patients. Moreover there is a need to identify IBC-specific targeted therapies to improve the curing prospects of this subtype of cancer.
    Archives of Gynecology 03/2015; DOI:10.1007/s00404-015-3691-4
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    ABSTRACT: Treatment side effects, comorbidities, and guideline-adherent treatment (GL+) influence the oncologic outcome of older breast cancer patients (oBCP) (age ≥ 70 years). The focus of this analysis was to investigate the associations among tumor characteristics, guideline adherence, and outcome and to compare these associations between younger breast cancer patients (yBCP) (age 50-69 years) and oBCP. This is a retrospective multicenter cohort study with 17 participating certified breast cancer centers. The analysis of 10,897 patient records collected from 1992 to 2008 for GL+ and clinical outcome was performed. Tumor and patient characteristics and their associations with GL+ were compared between oBCP and yBCP. Nonguideline-adherent treatment (GL-) was associated with higher tumor stages and comorbidities. This effect was stronger in the oBCP group (P < .001). GL+ was significantly more common in yBCP than in oBCP (P < .001). The oBCP had significantly higher tumor stages, including tumor size (P < .001), nodal status (P < .001), and positive hormone receptors (P = .001). Tumor grading was lower (P = .001), and HER2neu overexpression was less frequent (P = .003) in oBCP. Overall survival and disease-free survival are significantly impaired if GL- occurred in patients with breast cancer independently of age. GL- is associated with decreased disease-free survival and overall survival in both age groups. GL+ decreases advanced tumor characteristics in all age groups but significantly more in oBCP. If patients received GL+, we were unable to detect a statistical significant difference in the survival parameters. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Breast Cancer 03/2015; DOI:10.1016/j.clbc.2015.03.003
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    ABSTRACT: This paper describes the study design, methodology, cohort profile and self-reported diseases in the ophthalmological branch of the Gutenberg Health Study (GHS). The GHS is an ongoing, prospective, interdisciplinary, single-center, population-based cohort study in Germany. The main goals of the ophthalmological section are to assess the prevalence and incidence of ocular diseases and to explore risk factors, genetic determinants and associations with systemic diseases and conditions. The eye examination at baseline included a medical history, self-reported eye diseases, visual acuity, refractive errors, intraocular pressure, visual field, pachymetry, keratometry, fundus photography and tear sampling. The 5-year follow-up visit additionally encompassed optical coherence tomography, anterior segment imaging and optical biometry. The general examination included anthropometry; blood pressure measurement; carotid artery ultrasound; electrocardiogram; echocardiography; spirometry; cognitive tests; questionnaires; assessment of mental conditions; and DNA, RNA, blood and urine sampling. Of 15,010 participants (aged 35-74 years at the time of inclusion), ocular data are available for 14,700 subjects (97.9%). The mean visual acuity (standard deviation), mean spherical equivalent, median decimal visual acuity, and mean intraocular pressure were 0.08 (0.17) logMar, -0.42 (2.43) diopters, 0.9 and 14.24 (2.79) mm Hg, respectively. The frequencies of self-reported strabismus, glaucoma, surgery for retinal detachment and retinal vascular occlusions were 2.7%, 2.3%, 0.2% and 0.4%, respectively. The GHS is the most extensive dataset of ophthalmic diseases and conditions and their risk factors in Germany and one of the largest cohorts worldwide. This dataset will provide new insight in the epidemiology of ophthalmic diseases and related medical specialties.
    PLoS ONE 03/2015; 10(3):e0120476. DOI:10.1371/journal.pone.0120476
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    ABSTRACT: The tumor biology of older breast cancer patients (oBCP) is usually less aggressive, however applied adjuvant treatment is often less potent resulting in an impaired disease free survival and overall survival in this group. This study tries to answer the following questions for the biological subtypes of oBCP (70+ y): METHODS: Between 1992 and 2008 the BRENDA ('BRENDA' = quality of BREast caNcer care unDer evidence-bAsed guidelines) study group recorded medical data of 17 participating certified breast cancer centers in Germany. We performed a retrospective multi-center database analysis of 5632 patient records. Guideline-adherent-treatment (GL+) of oBCP(n = 1918) was compared to GL+ of yBCP(n = 3714). OBCP were more likely to have hormone receptor positive (HR+) and HER2neu negative (HER2-) breast cancer (77.5% vs 74.5%). The rate of GL- was significantly different (p < 0.001) between the age groups and the biological subgroups (yBCP vs oBCP: 21.8%vs38.8% (HR+/HER2-); 30.6%vs49.7% (HR+/HER2+); 23.6%vs69.5% (HR-/HER2+); 31.4%vs67.8% (TNBC)). The survival parameters for HR+/HER2- and TNBC were significantly worse in case of GL- regarding chemotherapy, and if applicable endocrine therapy. A similar association only existed in HR-/HER2+ tumors for GL- for radiotherapy and in HR+/HER2+ tumors for chemotherapy. Beside the significantly different distribution of biological subtypes in the age groups there is an association between biological subtype, and GL+ influencing survival parameters in oBCP. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Breast (Edinburgh, Scotland) 03/2015; 24(3). DOI:10.1016/j.breast.2015.02.029
  • Harald Binder, Maria Blettner
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    ABSTRACT: Inexpensive techniques for measurement and data storage now enable medical researchers to acquire far more data than can conveniently be analyzed by traditional methods. The expression "big data" refers to quantities on the order of magnitude of a terabyte (1012 bytes); special techniques must be used to evaluate such huge quantities of data in a scientifically meaningful way. Whether data sets of this size are useful and important is an open question that currently confronts medical science. In this article, we give illustrative examples of the use of analytical techniques for big data and discuss them in the light of a selective literature review. We point out some critical aspects that should be considered to avoid errors when large amounts of data are analyzed. Machine learning techniques enable the recognition of potentially relevant patterns. When such techniques are used, certain additional steps should be taken that are unnecessary in more traditional analyses; for example, patient characteristics should be differentially weighted. If this is not done as a preliminary step before similarity detection, which is a component of many data analysis operations, characteristics such as age or sex will be weighted no higher than any one out of 10 000 gene expression values. Experience from the analysis of conventional observational data sets can be called upon to draw conclusions about potential causal effects from big data sets. Big data techniques can be used, for example, to evaluate observational data derived from the routine care of entire populations, with clustering methods used to analyze therapeutically relevant patient subgroups. Such analyses can provide complementary information to clinical trials of the classic type. As big data analyses become more popular, various statistical techniques for causality analysis in observational data are becoming more widely available. This is likely to be of benefit to medical science, but specific adaptations will have to be made according to the requirements of the applications.
    Deutsches Ärzteblatt International 02/2015; 112(9):137-42. DOI:10.3238/arztebl.2015.0137
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    ABSTRACT: The purpose of the study was to determine anxiety and depression, quality of life, and their determinants in long-term survivors of malignant melanoma. In a state cancer registry a cohort of survivors of malignant melanoma was contacted via the physician registered. Of 1302 contactable patients, 689 (52.2%) completed a questionnaire including the Patient Health Questionnaire with generalized anxiety (GAD-7) and depression (PHQ-9) and the EORTC Quality of Life Questionnaire (EORTC QLQ 30). Based on multiple regression analysis, predictors of quality of life and distress were identified. Comparison data were assessed in two waves of representative face-to-face household surveys of the adult German population. An average of 8.4 (5.7 to 12.2) years after diagnosis, distress was higher in women compared to men and in middle adulthood (vs. older patients). Symptoms were higher in women than in men, and there was a decline of functioning and increase of symptoms across the age range of both genders. Compared to the general population, there were slightly increased depression and anxiety (only women), but no impaired global quality of life. Yet, survivors evidenced functional decline and more physical symptoms. Distress and reduced quality of life were consistently predicted by lack of social support, fear of recurrence, pessimism and self-blame. Distress was increased by a family history of melanoma, and additional mental and somatic diseases. Overall, long-term survivors have adjusted well achieving a global quality of life comparable to the general population. Yet, compromised functional dimensions, physical symptoms and distress indicate the need for integrating psychooncological screening into oncological follow-up, which might be guided by predictors such as family history or social support. Further prospective study is needed to determine the course of adaptation to the disease and corroborate the risk factors identified.
    PLoS ONE 01/2015; 10(1):e0116440. DOI:10.1371/journal.pone.0116440
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    ABSTRACT: Treatment-outcome associations often differ substantially between observational studies (OSs) and randomized controlled trials (RCTs). We investigate causes, focusing on radiotherapy (RT) effects in early breast cancer treatment, to better understand each study type's merits. We systematically analyzed three potential causes, by comparing data from a large OS with results from two previously published meta-analyses of RCTs: differences in patient populations combined with heterogeneous treatment effects, non-random treatment decisions in OSs, and differences in therapy administration. RT-survival associations were considerably stronger in our OS than in the RCTs, e.g., a hazard rate for overall survival after breast-conserving therapy of 0.57 in the OS vs 0.90 in the RCTs. The first proposed reason has limited relevance: patient populations differed considerably, but effect heterogeneity between patient groups was limited. The second reason does explain part of the difference: in the OS treatment decisions (being nonrandomized) and prospects differed with patient characteristics. Notably, patients with early recurrences or mortality are generally excluded from RCTs. Their inclusion in OSs leads to stronger treatment-outcome associations. RCTs and OSs each have their own merits. While RCTs have their undisputed benefits, results from OSs that indicate that RT effects in early breast cancer are even stronger than those reported in RCTs should not be ignored.
    Breast Cancer 01/2015; DOI:10.1007/s12282-014-0579-2
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    ABSTRACT: The aim of this cohort study was to assess the risk of developing cancer, specifically leukaemia, tumours of the central nervous system and lymphoma, before the age of 15 years in children previously exposed to computed tomography (CT) in Germany. Data for children with at least one CT between 1980 and 2010 were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010 were identified by stochastic linkage with the German Childhood Cancer Registry (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed to assess the underlying medical conditions at time of the CT. Cases were only included if diagnosis occurred at least 2 years after the first CT and no signs of cancer were recorded in the radiology reports. Standardised incidence ratios (SIR) using incidence rates from the general population were estimated. The cohort included information on 71,073 CT examinations in 44,584 children contributing 161,407 person-years at risk with 46 cases initially identified through linkage with the GCCR. Seven cases had to be excluded due to signs possibly suggestive of cancer at the time of first CT. Overall, more cancer cases were observed (O) than expected (E), but this was mainly driven by unexpected and possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was 1.72 (95 % CI 0.89-3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI 0.54-2.78, O = 7). Despite careful examination of the medical information, confounding by indication or reverse causation cannot be ruled out completely and may explain parts of the excess. Furthermore, the CT exposure may have been underestimated as only data from the participating clinics were available. This should be taken into account when interpreting risk estimates.
    Biophysik 01/2015; 54(1). DOI:10.1007/s00411-014-0580-3
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    ABSTRACT: Introduction: We investigated how many cancer survivors receive psycho-oncological care in hospitals and outpatient cancer counselling centres and which factors influence usage. Methods: Long-term survivors of breast, colon or prostate cancer completed a questionnaire assessing the use of psycho-oncological services in the "Cancer Survivorship - a multiregional population-based study (CAESAR)". Gender, age, community size, education, income and stage of disease were investigated as potential predictors of use. Results: Out of 6 143 participants, 547 (9%) reported having received psycho-oncological support in the hospital, 183 (3%) had visited a counselling centre. Inpatient services were more frequently used by higher educated persons (OR 1.5), women (OR 1.3), and patients with advanced disease (OR 1.3); less frequently by older survivors (OR 0.6). Community size and income were not related to inpatient use. Counselling centres were visited more frequently by women (OR 2.2), higher educated survivors (OR 2.1), patients with advanced disease (OR 1.6), and participants from communities with >100 000 inhabitants (OR 2.4); less frequently from elderly OR 0.4). Discussion: Especially the use of outpatient cancer counselling centres was associated with contextual and individual factors whereas this was not so much the case with the use of inpatient services. This implies that care models where psycho-oncologists actively approach patients are better able to access all patient groups in contrast to care models where patients have to actively seek help. It also implies that non-use not necessarily means that patients do not need help but that there are barriers to health care access. © Georg Thieme Verlag KG Stuttgart · New York.
    PPmP - Psychotherapie · Psychosomatik · Medizinische Psychologie 12/2014; DOI:10.1055/s-0034-1395627
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    ABSTRACT: Malignant germ cell tumors (GCTs) are a rare and a heterogeneous group of pediatric cancers. The incidence rate has increased in some populations or subgroups. However, only a few recent publications on epidemiologic data showing the trends in incidence of pediatric GCTs are available. We analyzed the incidence rates, time trends, and survival for 1366 GCTs in children 0 to 14 years old registered in the nationwide, population-based German Childhood Cancer Registry in 1987-2011. The incidence rate of GCTs was slightly higher in girls (age-standardized rate: girls, 5.3; boys, 4.4 per million). A bimodal age distribution was seen. In children aged <1 year, the highest age-specific incidence rates were seen for girls with GCTs in the pelvis (12.7 per million) and for boys with GCTs in the testis (9.5 per million). For 10- to 14-year-old boys, the tumors occurred most often in the central nervous system (3.1 per million); for girls, the most common site was in the ovaries (4.5 per million). Only the incidence rate for ovarian GCTs increased statistically significantly. The 5- and 20-year survival probabilities for the patients diagnosed between 1987 and 2010 were 92% and 90%, respectively. Survival rates improved notably for intracranial and extragonadal GCTs from 1987 to 2006. The localization and histology of the GCTs varied between the genders and age groups. During 1987 to 2011, the incidence rate increased only for ovarian GCTs. The increase, however, may be due to changes in reporting. The survival rates were excellent. Copyright © 2015 by the American Academy of Pediatrics.
    Pediatrics 12/2014; 135(1). DOI:10.1542/peds.2014-1989

Publication Stats

10k Citations
1,419.62 Total Impact Points


  • 2009–2015
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
      • Institute for Medical Biometry, Epidemiology and Computer Science
      Mayence, Rheinland-Pfalz, Germany
  • 2006–2015
    • Johannes Gutenberg-Universität Mainz
      • • Division of Medical Biometry I
      • • Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI)
      Mayence, Rheinland-Pfalz, Germany
    • National Institutes of Health
      • Branch of Radiation Epidemiology
      Bethesda, MD, United States
  • 2000–2015
    • Universitätsklinikum Freiburg
      • • Department of Ophthalmology
      • • Institute of Medical Biometry and Statistics
      Freiburg an der Elbe, Lower Saxony, Germany
  • 2014
    • University of Surrey
      • Faculty of Health and Medical Sciences
      Guilford, England, United Kingdom
  • 2004–2014
    • Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V.
      Mayence, Rheinland-Pfalz, Germany
  • 2011
    • Universitätsklinikum Münster
      • Institut für Biometrie und Klinische Forschung
      Muenster, North Rhine-Westphalia, Germany
  • 2010
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 2005–2007
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
    • Technische Universität Berlin
      Berlín, Berlin, Germany
  • 1999–2005
    • Bielefeld University
      • School of Public Health
      Bielefeld, North Rhine-Westphalia, Germany
  • 1991–1998
    • University of Freiburg
      • Institute of Medical Biometry and Medical Informatics
      Freiburg, Lower Saxony, Germany
    • National Cancer Institute (USA)
      • Radiation Epidemiology
      Maryland, United States
  • 1996–1997
    • Heidelberger Akademie der Wissenschaften
      Heidelburg, Baden-Württemberg, Germany
    • Universitätsklinikum Erlangen
      • Department of Dermatology
      Erlangen, Bavaria, Germany
  • 1986–1996
    • German Cancer Research Center
      • Division of Cancer Epidemiology
      Heidelburg, Baden-Württemberg, Germany