Publications by authors named "Nadia Obi"

46 Publications

Health-Related Quality of Life in a Cohort of Breast Cancer Survivors over More Than 10 Years Post-Diagnosis and in Comparison to a Control Cohort.

Cancers (Basel) 2021 Apr 13;13(8). Epub 2021 Apr 13.

Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.

Breast cancer (BC) survivors often suffer from late and long-term residual symptoms of the disease and its treatment. To date, long-term health-related quality of life (HRQoL) in breast cancer survivors has been seldom investigated and rarely compared to unaffected women (controls). This study aimed to investigate HRQoL over time using patient-reported status before diagnosis, during treatment, 1 year post-surgery, approx. 5 years and ≥10 years post-diagnosis. We also compared survivors' HRQoL with controls' still alive 10 years after recruitment. Data from the German population-based Mamma Carcinoma Risk Factor Investigation (MARIE) cohort of 1123 BC patients aged 50-74 years at diagnosis (2002-2005) and of 3453 matched controls were used for analysis. HRQoL was assessed with the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) questionnaire. All analyses were conducted for all ages as well as stratified according to three age groups (≤58 years, 59-64 years, ≥64 years). Differences in survivors' general HRQoL before, during, and after therapy were investigated using a t-test/Wilcoxon signed-rank test. Changes in the HRQoL of survivors stratified by age from FU1 to FU2 were assessed via repeated analysis of variance. The HRQoL of survivors compared to the controls at FU2 was analyzed using an analysis of variance. Over all ages, the general HRQoL in patients improved in the first 5 years post-diagnosis. In the subsequent years, HRQoL slightly deteriorated but was comparable to that of the controls. Younger survivors mostly improved their HRQoL from the 5 to 10-year follow-up but remained negatively affected for most functioning and symptom scales compared to controls. In older survivors, HRQoL hardly changed over time and detriments were less pronounced compared to controls, except for insomnia. Restrictions of HRQoL persist for more than 10 years and are most prominent among younger survivors. Researchers and clinicians should be aware of such potential deteriorations and age-dependent differences in order to optimize/adapt long-term cancer survivor care.
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http://dx.doi.org/10.3390/cancers13081854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069882PMC
April 2021

Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium.

Cancer Epidemiol Biomarkers Prev 2021 Apr 26;30(4):623-642. Epub 2021 Jan 26.

Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.

Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.

Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.

Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype ( > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking.

Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.

Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026532PMC
April 2021

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.

Br J Cancer 2021 Feb 26;124(4):842-854. Epub 2021 Jan 26.

Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk.

Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry.

Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10).

Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
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http://dx.doi.org/10.1038/s41416-020-01185-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884683PMC
February 2021

Comorbidity burden in long-term breast cancer survivors compared with a cohort of population-based controls from the MARIE study.

Cancer 2021 Apr 1;127(7):1154-1160. Epub 2020 Dec 1.

Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: The number of elderly cancer survivors is growing because of increasing survival rates. A high comorbidity burden in the elderly can affect their quality of life and survival. The aim of this study was to examine whether breast cancer survivors and population-based controls have a different comorbidity burden after long-term follow-up.

Methods: This study used data from a German breast cancer case-control study, which initially comprised 3813 breast cancer cases aged 50 to 74 years who were diagnosed between 2002 and 2005 and 7341 population-based controls. Participants were followed up in 2014/2016. A modified Charlson Comorbidity Index (mCCI) was calculated to quantify severe comorbidities. Negative binomial regression was performed to estimate rate ratios (RRs) with 95% confidence intervals (CIs) for the association between case-control status and mCCI (dependent variable) for the baseline population and for those who participated at follow-up, with adjustments made for relevant lifestyle factors.

Results: In total, 1925 cases and 3674 controls participated in the follow-up 12 years after recruitment. In the baseline population 35% had at least 1 comorbid condition.In long-term survivors this proportion was 52%. No difference was found in the mCCI between breast cancer cases and controls at baseline (RR, 1.05; 95% CI, 0.98-1.11) or between long-term survivors of the 2 groups at baseline (RR, 1.07; 95% CI, 0.97-1.18) or at follow-up (RR, 1.00; 95% CI, 0.91-1.10).

Conclusions: The comorbidity burden of long-term breast cancer survivors and controls increased over time; however, it remained similar in both groups after 12 years of follow-up.
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http://dx.doi.org/10.1002/cncr.33363DOI Listing
April 2021

Changes in alcohol consumption, body weight and physical activity among breast cancer survivors and population-based unaffected women in a prospective study.

Cancer Epidemiol 2021 02 19;70:101852. Epub 2020 Nov 19.

Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), Medical Center Hamburg-Eppendorf (UKE), Martinistr. 52, 20246 Hamburg, Germany; Department of Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address:

Background: It is unclear whether a breast cancer diagnosis affects health behaviour changes that occur with ageing. We aimed to compare long-term changes of alcohol consumption, body weight, and physical activity in women with breast cancer and in age-matched unaffected women.

Methods: We used data from 1,925 women with breast cancer and 3,473 unaffected women aged 50-74 years enrolled in the population-based case-control study MARIE (Mamma Carcinoma Risk Factor Investigation) in 2002-2005, who also completed the follow-up in 2014-2016. Multinomial logistic regression was applied to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between breast cancer status and categories of change in alcohol consumption, weight and physical activity.

Results: After 11.6 years of follow-up, breast cancer survivors had significantly lower odds than unaffected women of increasing alcohol consumption from ≤10 to >10 g/day (adjusted OR 0.48, 95 % CI 0.35-0.65), but were more likely to experience a major weight change of ≥10 % compared to having stable weight (±<5 %) (OR for increase and decrease 1.32, 95 % CI 1.03-1.70 and 1.36, 95 % CI 1.05-1.77, resp.) and to decrease transport physical activity to below 2.5 h/week compared to maintaining the activity level (OR 1.61, 95 % CI 1.26-2.04). No significant group difference was found for changes in recreational physical activity.

Conclusion: Our data indicate that some long-term health behaviour changes can be attributed to a breast cancer diagnosis rather than ageing, suggesting that long-term medical care of breast cancer survivors could pay greater attention to weight control and sufficient physical activity.
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http://dx.doi.org/10.1016/j.canep.2020.101852DOI Listing
February 2021

Postdiagnosis weight change is associated with poorer survival in breast cancer survivors: A prospective population-based patient cohort study.

Int J Cancer 2021 Jan 10;148(1):18-27. Epub 2020 Jul 10.

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

More women are surviving after breast cancer due to early detection and modern treatment strategies. Body weight also influences survival. We aimed to characterize associations between postdiagnosis weight change and prognosis in postmenopausal long-term breast cancer survivors. We used data from a prospective population-based patient cohort study (MARIE) conducted in two geographical regions of Germany. Breast cancer patients diagnosed 50 to 74 years of age with an incident invasive breast cancer or in situ tumor were recruited from 2002 to 2005 and followed up until June 2015. Baseline weight was ascertained at an in-person interview at recruitment and follow-up weight was ascertained by telephone interview in 2009. Delayed entry Cox proportional hazards regression was used to assess associations between relative weight change and all-cause mortality, breast cancer mortality, and recurrence-free survival. In total, 2216 patients were included. Compared to weight maintenance (within 5%), weight loss >10% increased risk of all-cause mortality (HR 2.50, 95% CI 1.61, 3.88), breast cancer mortality (HR 3.07, 95% CI 1.69, 5.60) and less so of recurrence-free survival (HR 1.43, 95% CI 0.87, 2.36). Large weight gain of >10% also increased all-cause mortality (HR 1.64, 95% CI 1.02, 2.62) and breast cancer mortality (HR 2.25, 95% CI 1.25, 4.04). Weight maintenance for up to 5 years in long-term breast cancer survivors may help improve survival and prognosis. Postdiagnosis fluctuations in body weight of greater than 10% may lead to increased mortality. Survivors should be recommended to avoid large deviations in body weight from diagnosis onwards to maintain health and prolong life.
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http://dx.doi.org/10.1002/ijc.33181DOI Listing
January 2021

[Frequencies of musculoskeletal symptoms and disorders in the population-based German National Cohort (GNC)].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Apr;63(4):415-425

Lehrstuhl für Epidemiologie, am UNIKA-T, LMU München, Augsburg, Deutschland.

Background: Musculoskeletal diseases and symptoms are very common in the general population. They lead to high healthcare costs and pose a significant burden to the national economy.

Objectives: Based on data from the population-based German National Cohort (GNC), frequencies of musculoskeletal symptoms and diseases are reported, including back pain, osteoporosis, osteoarthritis, and arthritis.

Materials And Methods: Data were collected from March 2014 to March 2017 in adults aged 20-75 years during the first half of the baseline survey of the GNC. The sample comprised 101,779 interviewed subjects, including 9370 subjects who underwent clinical musculoskeletal examinations. The interview included questions about specific musculoskeletal disorders. A clinical examination of the hand provided information about palpable swollen joints and pressure-sensitive joints. Resting pain of the knees and hips was also assessed by a clinical examination. Frequencies were standardized to the German standard population of the year 2011.

Results: Having ever been diagnosed with recurrent back pain (22.5%) or osteoarthritis (20.6%) were the most common complaints reported in the interview; osteoporosis (2.9%) and rheumatoid arthritis (1.9%) were stated more seldom. According to the hand examination, 6.0% of all participants experienced pain in at least one finger joint. Resting pain was present in at least one knee among 8.2% and in at least one hip among 5.1% of the participants as assessed during the clinical examination. Women were more likely to report musculoskeletal disorders and symptoms than men. The proportion of adults affected by musculoskeletal diseases increased strongly with age.

Conclusion: Musculoskeletal disorders and symptoms occur frequently. The burden of complaints and diagnoses is comparable to previous population-based surveys.
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http://dx.doi.org/10.1007/s00103-020-03110-1DOI Listing
April 2020

[Self-reported infections in the German National Cohort (GNC) in the context of the current research landscape].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Apr;63(4):404-414

Abteilung Epidemiologie von Krebserkrankungen, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland.

Background: Infectious diseases continue to play an important role for disease perception, health-economic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pave the way for new targeted approaches in disease prevention.

Objectives: The aim was to describe the tools used to assess infectious diseases and to present initial data on infectious disease frequencies, as well as to relate the GNC assessment tools to data collection methods in other studies in Germany.

Methods: As part of the baseline examination, questions regarding infectious diseases were administered using both an interview and a self-administered touchscreen questionnaire. Data from the initial 101,787 GNC participants were analysed.

Results: In the interview, 0.2% (HIV/AIDS) to 8.6% (shingles) of respondents reported ever having a medical diagnosis of shingles, postherpetic neuralgia (in cases where shingles was reported), hepatitis B/C, HIV/AIDS, tuberculosis or sepsis if treated in hospital. In the questionnaire, 12% (cystitis) to 81% (upper respiratory tract infections) of respondents reported having experienced at least one occurrence of upper or lower respiratory tract infections, gastrointestinal infections, cystitis or fever within the past 12 months.

Outlook: The cross-sectional analyses of data and tools presented here - for example on determinants of susceptibility to self-reported infections - can be anticipated from the year 2021 onward. Beyond that, more extensive research into infectious disease epidemiology will follow, particularly once analyses of GNC biological materials have been performed.
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http://dx.doi.org/10.1007/s00103-020-03114-xDOI Listing
April 2020

[Self-reported cancer in the German National Cohort (NAKO Gesundheitsstudie): assessment methods and first results].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Apr;63(4):385-396

Institut für Medizinische Epidemiologie, Biometrie und Informatik, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland.

Background: In the German National Cohort (NAKO Gesundheitsstudie), the largest prospective cohort study in Germany, data on self-reported cancer diagnoses are now available for the first half of participants.

Objectives: Description of the methods to assess self-reported cancer diagnoses and type of cancer in the NAKO and presentation of first results.

Materials And Methods: In a computer-assisted, standardized personal interview, 101,787 participants (54,526 women, 47,261 men) were asked whether they had ever been diagnosed with cancer (malignant tumors including in situ) by a physician and how many cancer diagnoses they had. The type of cancer was classified with a list. Absolute and relative frequencies of self-reported cancer diagnoses and types of cancer were calculated and compared with cancer registry data.

Results: A physician-diagnosed cancer was reported by 9.4% of women and 7.0% of men. Of the participants who reported a cancer diagnosis, 88.3% reported to have had only one cancer diagnosis. In women, the most frequent malignancies were breast cancer, cervical cancer, and melanoma. In men, the most frequent malignancies were prostate cancer, melanoma, and colorectal cancer. Comparing the frequencies of cancer diagnoses reported by 45- to 74-year-old NAKO participants within the last five years to cancer registry-based 5‑year prevalences, most types of cancer were less frequent in the NAKO, with the exception of melanoma in men and women, cervical cancer and liver cancer in women, and bladder cancer and breast cancer in men.

Conclusions: The NAKO is a rich data basis for future investigations of incident cancer.
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http://dx.doi.org/10.1007/s00103-020-03113-yDOI Listing
April 2020

[Design and quality control of the oral health status examination in the German National Cohort (GNC)].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Apr;63(4):426-438

Institut für Epidemiologie und Sozialmedizin, Westfälische Wilhelms-Universität Münster, Münster, Deutschland.

Background: Caries and periodontitis are highly prevalent worldwide. Because detailed data on these oral diseases were collected within the framework of the German National Cohort (GNC), associations between oral and systemic diseases and conditions can be investigated.

Objectives: The study protocol for the oral examination was designed to ensure a comprehensive collection of dental findings by trained non-dental staff within a limited examination time. At the mid-term of the GNC baseline examination, a first quality evaluation was performed to check the plausibility of results and to propose measures to improve the data quality.

Materials And Methods: A dental interview, saliva sampling and oral diagnostics were conducted. As part of the level‑1 examination, the number of teeth and prostheses were recorded. As part of the level‑2 examination, detailed periodontal, cariological and functional aspects were examined. All examinations were conducted by trained non-dental personnel. Parameters were checked for plausibility and variable distributions were descriptively analysed.

Results: Analyses included data of 57,967 interview participants, 56,913 level‑1 participants and 6295 level‑2 participants. Percentages of missing values for individual clinical parameters assessed in level 1 and level 2 ranged between 0.02 and 3.9%. Results showed a plausible distribution of the data; rarely, implausible values were observed, e.g. for measurements of horizontal and vertical overbite (overjet and overbite). Intra-class correlation coefficients indicated differences in individual parameters between regional clusters, study centres and across different examiners.

Conclusions: The results confirm the feasibility of the study protocol by non-dental personnel and its successful integration into the GNC's overall assessment program. However, rigorous dental support of the study centres is required for quality management.
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http://dx.doi.org/10.1007/s00103-020-03107-wDOI Listing
April 2020

[Physical activity in the German National Cohort (NAKO): use of multiple assessment tools and initial results].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Mar;63(3):301-311

Institut für Medizinische Informatik, Biometrie und Epidemiologie (IMIBE), Universitätsklinikum Essen, Essen, Deutschland.

Background: Physical activity is a complex behavior that is difficult to measure validly and reliably in large, population-based studies. Data on physical activity are available for the initial 100,000 participants of the German National Cohort.

Objectives: To describe the baseline physical activity assessment in the cohort and to present initial descriptive results.

Material And Methods: Physical activity was assessed using a combination of tools, including two self-administered questionnaires, the Questionnaire on Annual Physical Activity Pattern (QUAP) and the Global Physical Activity Questionnaire (GPAQ); a computer-based 24‑h physical activity recall (cpar24); and 7‑day accelerometry (Actigraph GT3X/+; ActiGraph, Pensacola, FL, USA).

Results: The availability of data varied between assessment instruments (QUAP: n = 16,372; GPAQ: n = 90,900; cpar24: n = 23,989; accelerometry: n = 35,218). Analyses across measurement tools showed that on average, women spent 75 to 216 min/d, and men spent 73 to 224 min/d in moderate or higher intensity total physical activity. Persons aged 20-39 years spent 66 to 200 min/d, and persons aged 40-69 years spent 78 to 244 min/d in moderate or higher intensity total physical activity.

Conclusions: Initial baseline analyses of physical activity in this cohort show the value of using a combination of questionnaires, 24‑h recalls, and a movement sensor. The comprehensive data collection represents a valuable resource for future analyses and will improve our understanding of the association between physical activity and disease prevention.
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http://dx.doi.org/10.1007/s00103-020-03099-7DOI Listing
March 2020

[Nighttime transportation noise annoyance in Germany: personal and regional differences in the German National Cohort Study].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Mar;63(3):332-343

Institut für Community Medicine, Universitätsmedizin Greifswald, Greifswald, Deutschland.

Background: Noise annoyance is associated with adverse health-related conditions and reduced wellbeing. Thereby, subjective noise annoyance depends on the objective noise exposure and is modified by personal and regional factors.

Objective: How many participants of the German National Cohort Study (GNC; NAKO Gesundheitsstudie) were annoyed by transportation noise during nighttime and what factors were associated with noise annoyance?

Materials And Methods: This cross-sectional analysis included 86,080 participants from 18 study centers, examined from 2014 to 2017. We used multinomial logistic regression to investigate associations of personal and regional factors to noise annoyance (slightly/moderately or strongly/extremely annoyed vs. not annoyed) mutually adjusting for all factors in the model.

Results: Two thirds of participants were not annoyed by transportation noise during nighttime and one in ten reported strong/extreme annoyance with highest percentages for the study centers Berlin-Mitte and Leipzig. The strongest associations were seen for factors related to the individual housing situation like the bedroom being positioned towards a major road (OR of being slightly/moderately annoyed: 4.26 [95% CI: 4.01;4.52]; OR of being strongly/extremely annoyed: 13.36 [95% CI: 12.47;14.32]) compared to a garden/inner courtyard. Participants aged 40-60 years and those in low- and medium-income groups reported greater noise annoyance compared to younger or older ones and those in the high-income group.

Conclusion: In this study from Germany, transportation noise annoyance during nighttime varied by personal and regional factors.
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http://dx.doi.org/10.1007/s00103-020-03094-yDOI Listing
March 2020

[Socio-demographic and employment-related factors in the German National Cohort (GNC; NAKO Gesundheitsstudie)].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Mar;63(3):267-278

Institut für Prävention und Tumorepidemiologie, Universitätsklinikum Freiburg, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg, Deutschland.

Background: In epidemiologic studies, standardised measurement of socio-demographic and employment-related factors is becoming increasingly important, as variables such as gender, age, education or employment status are factors influencing health and disease risks.

Aims: The article gives an overview of the scientific background and assessment of socio-demographic factors in the German National Cohort Study. In addition, the distribution of individual characteristics in the cohort as well as relationships with health-related measures are presented by way of example.

Material And Methods: The analysis is based on the data of the first half of the baseline survey (n = 101,724). On this basis, we present the distribution of key socio-demographic characteristics and analyse relationships with exemplary selected health indicators (body mass index, self-reported health) to assess the validity of socio-demographic data measurements.

Results: On average, study participants were 52.0 years old (SD = 12.4). Of the participants, 53.6% were women, 54.3% had high education, 60.1% were married and 72% were employed while 3.4% were unemployed. Well-established correlations between socio-demographic factors and health could be reproduced with the German National Cohort data. For example, low education, old age and unemployment were associated with an increased prevalence of obesity and poor self-reported health.

Discussion: The German National Cohort provides a comprehensive measurement of socio-demographic characteristics. Combined with a wide range of health data and the longitudinal measurements available in the future, this opens up new opportunities for health science and social epidemiological research in Germany.
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http://dx.doi.org/10.1007/s00103-020-03098-8DOI Listing
March 2020

[Persons with migration background in the German National Cohort (NAKO)-sociodemographic characteristics and comparisons with the German autochthonous population].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Mar;63(3):279-289

Institut für Community Medicine, Universitätsmedizin Greifswald, Greifswald, Deutschland.

Background: Persons with a migration background (PmM) as a population group usually differ from the autochthonous population in terms of morbidity, mortality, and use of the health care system, but they participate less frequently in health studies. The PmM group is very heterogeneous, which has hardly been taken into account in studies so far.

Objectives: Sociodemographic characteristics of PmM in the NAKO health study (age, sex, time since migration, education) are presented. In addition, it is examined through an example whether migration background is related to the use of cancer screening for colorectal cancer (hemoccult test).

Methods: Data of the first 101,816 persons of the NAKO were analyzed descriptively and cartographically. The migration background was assigned on the basis of the definition of the Federal Statistical Office, based on nationality, country of birth, year of entry, and country of birth of the parents.

Results: Overall, the PmM proportion is 16.0%. The distribution across the 18 study centers varies considerably between 6% (Neubrandenburg) and 33% (Düsseldorf). With 153 countries of origin, most countries are represented in the NAKO. All variables show clear differences between the different regions of origin. In the hemoccult test, persons of Turkish origin (OR = 0.67) and resettlers (OR = 0.60) have a lower participation rate. PmM born in Germany do not differ in this respect from the autochthonous population (OR = 0.99).

Conclusion: PmM in the NAKO are a very heterogeneous group. However, due to the sample size, individual subgroups of migrants can be studied separately with respect to region of origin.
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http://dx.doi.org/10.1007/s00103-020-03097-9DOI Listing
March 2020

[Anthropometric measures in the German National Cohort-more than weight and height].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Mar;63(3):290-300

Abteilung Klinische Epidemiologie und Alternsforschung, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland.

High levels of adiposity in the population have a major impact on various diseases, but previous epidemiologic studies have largely been restricted to simple anthropometric measures such as the body mass index (BMI), an imperfect predictor of disease risk. There is a critical need for the use of improved measures of relative weight and body composition in large-scale, population-based research.The current article presents initial descriptive results of body composition and fat distribution based on the midterm baseline dataset of the German National Cohort, which included 101,817 participants who were examined in 18 study centers in Germany between March 2014 and March 2017. The anthropometric measures encompassed body weight, height, waist and hip circumference, bioelectrical impedance analysis (BIA), sonography of abdominal adipose tissue, 3D-body scanning, and magnetic resonance imaging.BMI analyses showed that 46.2% of men and 29.7% of women were overweight and 23.5% of men and 21.2% of women were obese. On average, women in almost all age groups demonstrated more subcutaneous adipose tissue layer thickness than men. The mean values of visceral adipose tissue layer thickness, on the other hand, were higher among men than among women in all age groups and increased continuously across age groups in both sexes.The comprehensive assessment of body composition and fat distribution provides novel future opportunities for detailed epidemiologic analyses of overweight and adiposity in relation to the development of chronic diseases.
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http://dx.doi.org/10.1007/s00103-020-03096-wDOI Listing
March 2020

Factors associated with habitual time spent in different physical activity intensities using multiday accelerometry.

Sci Rep 2020 01 21;10(1):774. Epub 2020 Jan 21.

Molecular Epidemiology Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.

To investigate factors associated with time in physical activity intensities, we assessed physical activity of 249 men and women (mean age 51.3 years) by 7-day 24h-accelerometry (ActiGraph GT3X+). Triaxial vector magnitude counts/minute were extracted to determine time in inactivity, in low-intensity, moderate, and vigorous-to-very-vigorous activity. Cross-sectional associations with sex, age, body mass index, waist circumference, smoking, alcohol consumption, education, employment, income, marital status, diabetes, and dyslipidaemia were investigated in multivariable regression analyses. Higher age was associated with more time in low-intensity (mean difference, 7.3 min/d per 5 years; 95% confidence interval 2.0,12.7) and less time in vigorous-to-very-vigorous activity (-0.8 min/d; -1.4, -0.2), while higher BMI was related to less time in low-intensity activity (-3.7 min/d; -6.3, -1.2). Current versus never smoking was associated with more time in low-intensity (29.2 min/d; 7.5, 50.9) and less time in vigorous-to-very-vigorous activity (-3.9 min/d; -6.3, -1.5). Finally, having versus not having a university entrance qualification and being not versus full time employed were associated with more inactivity time (35.9 min/d; 13.0, 58.8, and 66.2 min/d; 34.7, 97.7, respectively) and less time in low-intensity activity (-31.7 min/d; -49.9, -13.4, and -50.7; -76.6, -24.8, respectively). The assessed factors show distinct associations with activity intensities, providing targets for public health measures aiming to increase activity.
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http://dx.doi.org/10.1038/s41598-020-57648-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972881PMC
January 2020

Pre- to postdiagnosis leisure-time physical activity and prognosis in postmenopausal breast cancer survivors.

Breast Cancer Res 2019 11 7;21(1):117. Epub 2019 Nov 7.

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: Physical activity (PA) before and after breast cancer diagnosis has been reported to be associated with lower mortality. However, whether changes in the activity after diagnosis impact prognosis is unclear and has not received much attention. This study aimed to examine pre- to postdiagnosis leisure-time PA and breast cancer prognosis.

Methods: We used data from the MARIE study, a prospective population-based patient cohort study of 3813 postmenopausal breast cancer patients, aged 50-74 at diagnosis, recruited from 2002 to 2005, re-interviewed in 2009, and followed up until June 2015. Prediagnosis PA was assessed at recruitment; postdiagnosis PA was assessed at re-interview in 2009. To examine pre- to postdiagnosis change in PA, women were categorized by pre- and postdiagnosis PA using a cut-off of 7.5 MET-h/week for meeting PA recommendations and combined into four groups: insufficiently active, increasingly active, decreasingly active, and sufficiently active. Cox regression models with delayed entry were used to assess associations between pre- to postdiagnosis patterns of PA and overall mortality (OM), breast cancer mortality (BCM), and recurrence-free survival (RFS). Additional analyses of pre- and postdiagnosis PA (no activity (reference), low activity, sufficient activity) with cancer outcomes, such as using a time-dependent model, were performed. In total, 2042 patients were included in the analyses.

Results: There were 206 deaths (114 from breast cancer) after a median follow-up time of 6.0 years after the 2009 interview. Compared to insufficiently active women, increasingly active women were at lower risk of OM, BCM, and RFS (HR (95%CI) of 0.50 (0.31-0.82), 0.54 (0.30-1.00), 0.58 (0.40-0.84), respectively). In sufficiently active women, associations for OM (0.75 (0.48-1.15)), BCM (0.61 (0.33-1.13)), and RFS 0.80 (0.57-1.14)) were similar to increasingly active women but attenuated, and decreasingly active women were not at lower risk for OM (0.91 (0.61-1.36)), BCM (0.80 (0.45-1.42)), and RFS (1.04 (0.76-1.43)). In time-dependent analyses, sufficient activity vs. no activity was associated with better OM (0.73 (0.57-0.93)), BCM (0.64 (0.46-0.89)), and RFS (0.82 (0.68-0.99)). Low activity was not significantly associated with prognosis.

Conclusion: Our data support benefits for breast cancer prognosis in being physically active pre- and postdiagnosis particularly for women who were insufficiently active prediagnosis.
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http://dx.doi.org/10.1186/s13058-019-1206-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836389PMC
November 2019

Prognostic associations of circulating phytoestrogens and biomarker changes in long-term survivors of postmenopausal breast cancer.

Nutr Cancer 2020 16;72(7):1155-1169. Epub 2019 Oct 16.

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Lignans are associated with improved postmenopausal breast cancer (BC) survival, but whether these associations, particularly with enterolactone (major lignan metabolite), persist over time is unclear. Little is known about other phytoestrogens on prognosis in long-term survivors. The study examines associations of prognosis with 1) circulating postdiagnosis enterolactone, 2) eight circulating phytoestrogen metabolites, and 3) changes in enterolactone and genistein. In a German cohort of 2,105 postmenopausal BC patients with blood samples collected at recruitment 2002-2005 (baseline) and re-interview in 2009 (follow-up), delay-entry Cox proportional hazards regression was used. Landmark analysis showed that circulating enterolactone (log2) associations with 5-year survival changed over time, with strongest hazard ratios of 0.89 (95% CI, 0.80-0.99) at blood draw (BD) and 0.86 (0.77-0.97) at 2 years post-BD for BC mortality, and 0.87 (0.80-0.95) at BD and 0.84 (0.76-0.92) at 3 years post-BD for all-cause mortality, which attenuated thereafter. In long-term survivors, increasing concentrations of genistein (1.17, 1.01-1.36), resveratrol (1.19, 1.02-1.40), and luteolin (1.96, 1.07-3.58) measured in follow-up blood samples were associated with poorer subsequent prognosis. Neither enterolactone at follow-up nor changes in enterolactone/genistein were associated with prognosis. Large long-term longitudinal studies with multiple phytoestrogen measurements are required to understand long-term effects of phytoestrogens after BC.
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http://dx.doi.org/10.1080/01635581.2019.1672762DOI Listing
May 2021

Herpes zoster incidence in Germany - an indirect validation study for self-reported disease data from pretest studies of the population-based German National Cohort.

BMC Infect Dis 2019 Jan 30;19(1):99. Epub 2019 Jan 30.

Institute for Medical Epidemiology, Biometry, and Informatics (IMEBI), Medical Faculty of the Martin Luther University Halle-Wittenberg, Magdeburger Str. 8, 06110, Halle (Saale), Germany.

Background: Until now, herpes zoster (HZ)-related disease burden in Germany has been estimated based on health insurance data and clinical findings. However, the validity of self-reported HZ is unclear. This study investigated the validity of self-reported herpes zoster (HZ) and its complication postherpetic neuralgia (PHN) using data from the pretest studies of the German National Cohort (GNC) in comparison with estimates based on health insurance data.

Methods: Data of 4751 participants aged between 20 and 69 years from two pretest studies of the GNC carried out in 2011 and 2012 were used. Based on self-reports of physician-diagnosed HZ and PHN, age- and sex-specific HZ incidence rates and PHN proportions were estimated. For comparison, estimates based on statutory health insurance data from the German population were considered.

Results: Eleven percent (95%-CI, 10.4 to 12.3, n = 539) of the participants reported at least one HZ episode in their lifetime. Our estimated age-specific HZ incidence rates were lower than previous estimates based on statutory health insurance data. The PHN proportion in participants older than 50 years was 5.9% (1.9 to 13.9%), which was in line with estimates based on health insurance data.

Conclusion: As age- and sex-specific patterns were comparable with that in health insurance data, self-reported diagnosis of HZ seems to be a valid instrument for overall disease trends. Possible reasons for observed differences in incidence rates are recall bias in self-reported data or overestimation in health insurance data.
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http://dx.doi.org/10.1186/s12879-019-3691-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354372PMC
January 2019

Antioxidant supplementation and breast cancer prognosis in postmenopausal women undergoing chemotherapy and radiation therapy.

Am J Clin Nutr 2019 01;109(1):69-78

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: There is a paucity of information on the prevalence of dietary supplement use in breast cancer survivors. Only a few studies have examined the impact of dietary supplements, particularly antioxidants, on breast cancer prognosis and the results are inconclusive.

Objective: We examined pre- and postdiagnosis use of supplements in postmenopausal breast cancer survivors in Germany and investigated associations between postdiagnosis use of antioxidants and other supplements, and prognosis (total and breast cancer mortality, and recurrence-free survival) both overall and in women who received chemotherapy and radiation therapy.

Design: Data from 2223 postmenopausal women diagnosed with nonmetastatic breast cancer from the population-based Mamma Carcinoma Risk Factor Investigation (MARIE) study were used. Women were interviewed at recruitment in 2002-2005 and again in 2009 and followed-up until 30 June 2015. Multivariate Cox regression analysis was used to estimate HRs and corresponding 95% CIs.

Results: Pre- and postdiagnosis supplement use was reported by 36% and 45% of the women, respectively. There were 240 deaths (134 from breast cancer) and 200 breast cancer recurrences after a median follow-up time of 6.0 y after the 2009 re-interview. After adjusting for relevant confounders, concurrent antioxidant use with chemotherapy or radiation therapy among 1940 women was associated with increased risk of total mortality (HR: 1.64; 95% CI: 1.01, 2.66) and worsened recurrence-free survival (HR: 1.84; 95% CI: 1.26, 2.68). Overall postdiagnosis supplement use was not associated with breast cancer prognosis.

Conclusions: Antioxidant use during chemotherapy or radiation therapy was associated with worsened breast cancer prognosis in postmenopausal women. There was no overall association between postdiagnosis supplement use and breast cancer prognosis. Results from our study align with the current recommendation to possibly avoid the use of antioxidants during chemotherapy or radiation therapy.
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http://dx.doi.org/10.1093/ajcn/nqy223DOI Listing
January 2019

Design and characterization of dietary assessment in the German National Cohort.

Eur J Clin Nutr 2019 11 15;73(11):1480-1491. Epub 2019 Jan 15.

Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.

Background/objectives: The aim of the study was to describe a novel dietary assessment strategy based on two instruments complemented by information from an external population applied to estimate usual food intake in the large-scale multicenter German National Cohort (GNC). As proof of concept, we applied the assessment strategy to data from a pretest study (2012-2013) to assess the feasibility of the novel assessment strategy.

Subjects/methods: First, the consumption probability for each individual was modeled using three 24 h food lists (24h-FLs) and frequencies from one food frequency questionnaire (FFQ). Second, daily consumed food amounts were estimated from the representative German National Nutrition Survey II (NVS II) taking the characteristics of the participants into account. Usual food intake was estimated using the product of consumption probability and amounts.

Results: We estimated usual intake of 41 food groups in 318 men and 377 women. The participation proportion was 100, 84.4, and 68.5% for the first, second, and third 24h-FL, respectively. We observed no associations between the probability of participating and lifestyle factors. The estimated distributions of usual food intakes were plausible and total energy was estimated to be 2707 kcal/day for men and 2103 kcal/day for women. The estimated consumption frequencies did not differ substantially between men and women with only few exceptions. The differences in energy intake between men and women were mostly due to differences in estimated daily amounts.

Conclusions: The combination of repeated 24h-FLs, a FFQ, and consumption-day amounts from a reference population represents a user-friendly dietary assessment approach having generated plausible, but not yet validated, food intake values in the pretest study.
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http://dx.doi.org/10.1038/s41430-018-0383-8DOI Listing
November 2019

Prognostic impact of surgery for early-stage invasive breast cancer on breast cancer-specific survival, overall survival, and recurrence risk: a population-based analysis.

Breast Cancer Res Treat 2018 Jul 19;170(2):381-390. Epub 2018 Mar 19.

Department of Cancer Epidemiology/Clinical Cancer Registry, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Purpose: Recent cohort studies demonstrated better overall survival (OS) or breast cancer-specific survival (BCS) for breast-conserving therapy (BCT) followed by radiation (RT) compared to mastectomy alone (MT). This is the first observational study in which adjustments for a comprehensive set of prognostic factors, adjuvant therapies, mode of detection, and comorbidities were possible to investigate OS, BCS, as well as recurrence risk of patients undergoing BCT + RT, MT + RT, or MT.

Methods: Women aged 50-74 years at diagnosis of early-stage invasive breast cancer (I-IIIa) between 2001 and 2005 at the German population-based case-control study (MARIE study) were recruited and followed prospectively as a case cohort until 2015. Kaplan-Meier estimates and stepwise adjusted multivariable Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI).

Results: The 2762 patients included were followed up for a median of 11.9 years (95% CI 11.8-12.0). 74.2% of patients underwent BCT + RT; 10.3% MT + RT and 15.6% MT alone. Compared to patients treated with MT alone, patients treated with BCT + RT showed non-statistically significant improved OS (HR 0.79, 95% CI 0.61-1.02), BCS (HR 0.79, 95% CI 0.55-1.12), and no difference in recurrence risks (HR 1.01, 95% CI 0.74-1.37). For patients treated with MT + RT, there were no differences in OS (HR 1.06, 95% CI 0.75-1.50), BCS (HR 1.17, 95% CI 0.75-1.82), or recurrence risk (HR 1.33, 95% CI 0.89-1.97).

Conclusions: Among patients with early-stage breast cancer, clinical outcomes more than 10 years after diagnosis did not differ between the primary treatment options BCT + RT, MT + RT versus MT alone after full adjustment.
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http://dx.doi.org/10.1007/s10549-018-4754-6DOI Listing
July 2018

Associations between adjuvant radiotherapy and different causes of death in a German breast cancer cohort.

Breast 2018 Apr 4;38:75-80. Epub 2018 Jan 4.

Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany; Department of Cancer Epidemiology/Clinical Cancer Registry, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Background: Studies of cohorts of breast cancer (BC) patients diagnosed before 1990 showed radiotherapy (RT) to be associated with increased cardiovascular (CVD) and lung cancer mortality many years after diagnosis. In the late 1990s, improvements in RT planning techniques reduced radiation doses to normal tissues. Recent studies did not consistently report higher RT-related mortality for CVD and second cancers. Aim of the study was to analyze specific causes of death after 3D-conformal RT in a recent BC cohort.

Methods: Stage I-III BC patients diagnosed 2001-2005 and enrolled in the population based MARIEplus study were followed-up for 11.9 years (median). Associations between adjuvant RT and cause-specific mortality were analyzed by using competing risks models, yielding subdistribution hazard ratios (SHR) for RT directly related to cumulative incidences. Models were adjusted for differences in baseline characteristics applying inverse-probability-of-treatment-weighting (IPTW).

Results: Of the 2951 patients, 2439 (83.0%) received RT. No significant association of RT with lung cancer mortality (SHR 0.88, 0.35-2.12), other cancer mortality (SHR 1.04, 95% CI 0.62-1.73) or cardiac mortality was observed (SHR 1.57, 0.75-3.29). Mortality from lung and other diseases were significantly lower in irradiated women (SHR 0.39, 95% CI 0.17-0.90 and SHR 0.58, 95% CI 0.34-0.97, respectively).

Conclusion: In line with recent studies, 3D-conformal RT did not significantly increase mortality from non-BC causes in the German MARIEplus cohort. Since long-term data are still sparse and event rates low in BC-cohorts, who received modern RT, investigation of possible late RT effects on mortality beyond 14 years of follow-up is warranted.
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http://dx.doi.org/10.1016/j.breast.2017.12.006DOI Listing
April 2018

Anti-nuclear autoantibodies in the general German population: prevalence and lack of association with selected cardiovascular and metabolic disorders-findings of a multicenter population-based study.

Arthritis Res Ther 2017 06 6;19(1):127. Epub 2017 Jun 6.

TWINCORE, Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Straße 7, 30625, Hannover, Germany.

Background: We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders.

Methods: We used data and blood samples from the pretest phases of the German National Cohort, obtained from six of the 18 study centers (n = 1199). All centers applied standardized instruments including face-to-face interviews, anthropometric measurements and collection of blood samples. Self-reported histories of diabetes mellitus, heart attack and elevated blood cholesterol and/or lipids were recorded. Height, weight and blood pressure were measured. ANAs were detected using a semi-automated system (AKLIDES®; Medipan GmbH, Dahlewitz, Germany). A positive ANA was defined as a titer ≥ 1:80. ANA were classified as weakly (1:80 or 1:160), moderately (1:320 or 1:640) or strongly (≥1:1280) positive. Specific autoantibodies against nuclear antigens were detected with second-step assays according to the ANA staining pattern. Associations between the assessed disorders and ANA positivity and pattern were examined using sex and age-adjusted mixed-effects logistic regression models.

Results: Thirty-three percent (95% confidence interval; 31-36%) of the 1196 participants (measurements could not be obtained from three samples) were ANA positive (titer ≥ 1:80). The proportions of weakly, moderately and strongly positive ANA were 29%, 3.3% and 1.3%, respectively. ANA positivity was more common among women than men across all titers (χ, p = 0.03). ANA positivity, even when stratified according to height of titer or immunofluorescent pattern, was not associated with diabetes, elevated blood cholesterol and/or lipids, obesity or hypertension. Second-step autoantibody assays were positive in 41 of the 83 samples (49%) tested, with anti-DFS70 (n = 13) and anti-dsDNA (n = 7) being most frequent. These subgroups were too small to test for associations with the disorders assessed.

Conclusions: The prevalence of ANA positivity in the German general population was similar to values reported from other countries. Contrary to other studies, there was no association with selected self-reported and objectively measured cardiovascular and metabolic variables.
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http://dx.doi.org/10.1186/s13075-017-1338-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461675PMC
June 2017

Determination of nasal and oropharyngeal microbiomes in a multicenter population-based study - findings from Pretest 1 of the German National Cohort.

Sci Rep 2017 05 12;7(1):1855. Epub 2017 May 12.

TWINCORE, Center for Experimental and Clinical Infection Research, Hannover, Germany.

We examined acceptability, preference and feasibility of collecting nasal and oropharyngeal swabs, followed by microbiome analysis, in a population-based study with 524 participants. Anterior nasal and oropharyngeal swabs were collected by certified personnel. In addition, participants self-collected nasal swabs at home four weeks later. Four swab types were compared regarding (1) participants' satisfaction and acceptance and (2) detection of microbial community structures based on deep sequencing of the 16 S rRNA gene V1-V2 variable regions. All swabbing methods were highly accepted. Microbial community structure analysis revealed 846 phylotypes, 46 of which were unique to oropharynx and 164 unique to nares. The calcium alginate tipped swab was found unsuitable for microbiome determinations. Among the remaining three swab types, there were no differences in oropharyngeal microbiomes detected and only marginal differences in nasal microbiomes. Microbial community structures did not differ between staff-collected and self-collected nasal swabs. These results suggest (1) that nasal and oropharyngeal swabbing are highly feasible methods for human population-based studies that include the characterization of microbial community structures in these important ecological niches, and (2) that self-collection of nasal swabs at home can be used to reduce cost and resources needed, particularly when serial measurements are to be taken.
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http://dx.doi.org/10.1038/s41598-017-01212-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431815PMC
May 2017

A Comprehensive Multistate Model Analyzing Associations of Various Risk Factors With the Course of Breast Cancer in a Population-Based Cohort of Breast Cancer Cases.

Am J Epidemiol 2016 Feb 27;183(4):325-34. Epub 2016 Jan 27.

We employed a semi-Markov multistate model for the simultaneous analysis of various endpoints describing the course of breast cancer. Results were compared with those from standard analyses using a Cox proportional hazards model. We included 3,012 patients with invasive breast cancer newly diagnosed between 2001 and 2005 who were recruited in Germany for a population-based study, the Mamma Carcinoma Risk Factor Investigation (MARIE Study), and prospectively followed up until the end of 2009. Locoregional recurrence and distant metastasis were included as intermediate states, and deaths from breast cancer, secondary cancer, and other causes were included as competing absorbing states. Tumor characteristics were significantly associated with all breast cancer-related endpoints. Nodal involvement was significantly related to local recurrence but more strongly related to distant metastases. Smoking was significantly associated with mortality from second cancers and other causes, whereas menopausal hormone use was significantly associated with reduced distant metastasis and death from causes other than cancer. The presence of cardiovascular disease at diagnosis was solely associated with mortality from other causes. Compared with separate Cox models, multistate models allow for dissection of prognostic factors and intermediate events in the analysis of cause-specific mortality and can yield new insights into disease progression and associated pathways.
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http://dx.doi.org/10.1093/aje/kwv163DOI Listing
February 2016

Relationship between menopausal hormone therapy and mortality after breast cancer The MARIEplus study, a prospective case cohort.

Int J Cancer 2016 May 30;138(9):2098-108. Epub 2015 Dec 30.

University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Cohort studies of breast cancer (BC) patients, but not of disease-free women at inclusion, have found menopausal hormone therapy (MHT) to be associated with decreased BC specific mortality (BCM). Here, the German population-based MARIEplus BC cohort was analyzed to further elucidate associations of prediagnostic MHT with BCM (and modification by tumor characteristics), recurrence, and secondarily with other cause and overall mortality. Enrolled 2002-2005, incident invasive BC cases (N = 3,321) were followed up for a median of 6.1 years. Cox proportional hazards models adjusted for tumor characteristics, mammography and lifestyle were applied. Compared with never users of MHT, current users at date of diagnosis had significantly lower BCM (Hazard ratio (HR) 0.72, 95% CI 0.53-0.97) and risk of recurrence (HR 0.61, 95% CI 0.46-0.82). The MHT related reduced BCM was confined to patients with low grade tumors (HR 0.44, 95% CI 0.28-0.70; phet  = 0.01) and not modified by estrogen receptor or nodal status. BCM decreased with MHT duration in current and increased in past users (phet  = 0.015). Mortality due to causes other than BC and overall mortality were also reduced in current MHT users (HR 0.51, 95% CI 0.32-0.81, HR 0.66, 95% CI 0.52-0.86, respectively). Favorable tumor characteristics and mammographic surveillance could not fully explain associations of current MHT use with BCM and recurrence risk. Thus, the study contributes to the evidence that prediagnostic MHT does not have a negative impact on prognosis after BC. The restriction of a reduced BCM to low grade tumors should be confirmed in independent studies.
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http://dx.doi.org/10.1002/ijc.29951DOI Listing
May 2016

Diverse recruitment strategies result in different participation percentages in a web-based study, but in similar compliance.

Int J Public Health 2015 Dec 14;60(8):937-43. Epub 2015 Sep 14.

Department of Epidemiology, Helmholtz Centre for Infection Research, Brunswick, Germany.

Objectives: We compared participation and compliance with a web-based data collection on infections among population-based samples recruited in different ways.

Methods: Individuals were recruited from participants in the German National Cohort study (Group A, n = 279) or persons who were invited to this study but did not participate (Group B, n = 53). A third group was invited to the web-based study only (Group C, n = 145).

Results: Response varied among groups between 3 % (B), 11 % (C) and 61 % (A), but compliance was similar (81-85 %). Response did not differ by age and sex. Compliance was lower among the youngest and oldest participants. In addition, participants currently not employed were more likely to have better compliance. Semi-parametric group-based modelling identified three distinct compliance trajectories; "poor compliance" (8 %), "improving compliance" (14 %) and "very good compliance" (78 %).

Conclusions: Participation differed among modes of recruitment, but compliance was similar among groups and notably high. Different recruitment approaches can be used and collected data can be combined to achieve greater sample sizes for longitudinal web-based studies.
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http://dx.doi.org/10.1007/s00038-015-0737-0DOI Listing
December 2015

Evaluation of a questionnaire to assess selected infectious diseases and their risk factors : findings of a multicenter study.

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2014 Nov;57(11):1283-91

Department of Epidemiology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124, Braunschweig, Germany,

Background/objectives: The risk to die from an infectious disease in Germany has been continuously decreasing over the last century. Since infections are, however, not only causes of death but risk factors for diseases like cardiovascular diseases, it is essential to monitor and analyze their prevalence and frequency, especially in consideration of the increased life expectancy. To gain more knowledge about infectious diseases as risk factors and their implications on the condition and change of the immune status, the German National Cohort (GNC), a population-based prospective cohort study, will recruit 200,000 subjects between 2014 and 2017. In Pretest 1, a feasibility study for the GNC, we evaluated a self-administered and self-report questionnaire on infectious diseases and on the use of health care facilities (hereinafter called "ID Screen") for feasibility and validity.

Methods: From August-November 2011, 435 participants between the ages of 20-69 completed the ID Screen. All subjects had been recruited via a random sample from the local residents' registration offices by 4 of the 18 participating study centers. The questionnaire encompasses 77 variables in six sections assessing items such as 12-month prevalence of infections, cumulative prevalence of infectious diseases, visit of health care facilities and vaccination. The feasibility was amongst others evaluated by assessing the completeness and comprehensiveness of the questionnaire. To assess the questionnaires ability to measure "immune status" and "susceptibility to infections", multivariate analysis was used.

Results: The overall practicability was good and most items were well understood, demonstrated by < 2/33 missing questions per questionnaire and only three variables: vaccination for influenza and pneumococci and infection with chickenpox had a frequency > 5 % of missing values. However, direct comparison of the items 12-month prevalence and lifetime prevalence of nephritis/pyelitis showed poor agreement and thereby poor understanding by 80 % of the participants, illustrating the necessity for a clear, lay person appropriate description of rare diseases to increase comprehensibility. The questionnaire will be used to support the assessment of immune dysfunction and frequency of infection. An analysis of these constructs in an exploratory factor analysis revealed limited applicability due to low interitem correlation (Cronbach's α < 0.5). This is corroborated by the extraction of more than one factor with a Kaiser-Meyer-Olkin measure of 0.6 instead of a unidimensional latent construct for "immune status".

Conclusion: All in all, the ID Screen is a good and reliable tool to measure infectious diseases as risk factors and outcome in general, but requires a better translation of infection specific terms into lay person terms. For the assessment of the overall immune status, the tool has strong limitations. Vaccinations status should also rather be assessed based on vaccination certificates than on participants' recall.
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http://dx.doi.org/10.1007/s00103-014-2052-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210746PMC
November 2014

Zoonoses research in the German National Cohort : feasibility of parallel sampling of pets and owners.

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2014 Nov;57(11):1277-82

Department of Biometry, Epidemiology and Information Processing, WHO Collaborating Centre for Research and Training in Veterinary Public Health, University of Veterinary Medicine Hannover, Foundation, Buenteweg 2, 30559, Hannover, Germany,

Cats and dogs live in more than 20 % of German households and the contact between these pets and their owners can be very close. Therefore, a transmission of zoonotic pathogens may occur. To investigate whether zoonotic research questions can be examined in the context of population-based studies like the German National Cohort (GNC), two studies on different study populations were conducted as part of the feasibility tests of the GNC. The aim of the first study was to quantify the actual exposure of participants of the GNC to cats and dogs. In the second study summarised here the feasibility of the sampling of cats and dogs by their owners was tested. To quantify the exposure of participants of the GNC to cats and dogs 744 study participants of the Pretests of the GNC were asked whether they had contact with animals. Currently 10 % have a dog and 14 % have a cat in their household. These figures confirm that a large proportion of the German population has contact with pets and that there is a need for further zoonoses research. To establish the collection of biological samples from cats and dogs in the context of large-scale population-based studies feasible methods are needed. Therefore, a study was conducted to test whether pet owners can take samples from their cats and dogs and whether the quality of these samples is comparable to samples taken by a qualified veterinarian. A total of 82 dog and 18 cat owners were recruited in two veterinary practices in Hannover and the Clinic for Small Animals at the University of Veterinary Medicine in Hannover. Sampling instructions and sample material for nasal and buccal swabs, faecal samples and, in the case of cat owners, a brush for fur samples, were given to the pet owners. The pet owners were asked to take the samples from their pets at home and to send the samples by surface mail. Swab samples were cultured and bacterial growth was quantified independent of bacterial species. The growth of Gram-positive and Gram-negative bacteria from samples taken by the veterinarian and the pet owners were compared. For Gram-positive bacteria the agreement of laboratory results was 71 % for nasal swabs and 78 % for oral swabs while for Gram-negative bacteria the agreement of laboratory results was 55 % for nasal swabs and 87 % for oral swabs. In conclusion it has been shown that participants of the GNC are exposed to cats and dogs and that the sampling of cats and dogs by their owners is a feasible method which can be a useful tool for zoonoses research in population-based studies.
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http://dx.doi.org/10.1007/s00103-014-2047-8DOI Listing
November 2014