Marina Arendt

Incidence of second cancers after radiotherapy and systemic chemotherapy in heritable retinoblastoma survivors: A report from the German reference center

Survivors of heritable retinoblastoma carry a high risk to develop second cancers. Eye‐preserving radiotherapy raises this risk, while the impact of chemotherapy remains less defined.

Pediatric second primary malignancies after retinoblastoma treatment

Children with retinoblastoma carry a high risk to develop second primary malignancies in childhood and adolescence. This study characterizes the type of pediatric second primary malignancies after retinoblastoma treatment and investigates the impact of different treatment strategies and prognostic factors at presentation.

Associations between former exposure to manganese and olfaction in an elderly population: Results from the Heinz Nixdorf Recall Study

HighlightsOlfaction tested in a population‐based cohort from a steel‐producing region.Cumulative exposure to inhalable Mn based on 4635 measurements.No association found between former exposure to Mn and impaired olfaction. Abstract Occupational exposure to manganese (Mn) has been associated with impairments in olfaction and motor functions, but it has yet to be determined if such effects persist upon cessation of exposure. The objective of this study was to evaluate the influence of former occupational Mn exposure on olfaction within the framework of a prospective cohort study among an elderly German population. Information on job tasks with recognized Mn exposure and data on odor identification assessed with Sniffin’ sticks was collected during the second follow‐up of the Heinz Nixdorf Recall Study. The study population consisted of 1385 men aged 55–86 years, 354 of whom ever worked in jobs with potential Mn exposure (median 58.3 &mgr;g/m3 years, interquartile range 19.0–185 &mgr;g/m3 years). Multiple exposure measures, including job tasks, cumulative Mn exposure, and Mn determined in blood samples (MnB) archived at baseline, were used to estimate effects of Mn on olfaction. Having ever worked as welder was associated with better olfaction compared to other blue‐collar workers without Mn exposure. Blue‐collar workers identified less odors in comparison to white‐collar workers. Concentrations of previous Mn exposure >185 &mgr;g/m3 years or MnB ≥15 &mgr;g/L were not associated with impaired olfaction. In addition to a strong age effect, participants with lower occupational qualification identified less odors. We found no relevant association of former Mn exposure at relatively low levels with impaired olfaction. Possible neurotoxic Mn effects may not be persistent after cessation.

The distribution of blood concentrations of lead (Pb), cadmium (Cd), chromium (Cr) and manganese (Mn) in residents of the German Ruhr area and its potential association with occupational exposure in metal industry and/or other risk factors

OBJECTIVE This study investigated the metal distribution in blood samples from the general population and the risk of having high metal concentration for metal workers. METHODS Metal concentrations were determined in archived blood samples from 1411 men and 1410 women (median age 59 and 57 years, respectively) collected at baseline (2000-2003) of the prospective Heinz Nixdorf Recall Study. Retrospective information on working in metal industry was obtained from previous follow-up survey (2011-2014). Odds ratios (ORs) with 95% confidence intervals (CI) of having a metal concentration >90th percentile (P90) for working in metal industry were calculated using logistic regression with adjustment for covariates. RESULTS More men than women worked in metal industry (57 vs. 3 at baseline). Male metal workers had increased blood lead (Pb) (OR: 2.86; 95% CI: 1.38-5.91) and manganese (Mn) (OR: 2.92; 95% CI: 1.46-5.81). Smoking (≥30 cigarettes/day) strongly influenced cadmium (Cd) in blood (OR: 168; 95% CI: 55-510). Women had higher Mn (8.92μg/L) and Cd (0.36μg/L) concentrations than men (Mn: 8.11μg/L; Cd: 0.29μg/L). Blood Pb in women (29.2μg/L) was lower than in men (33.2μg/L). None of the studied risk factors was significantly associated with chromium and nickel concentrations above their 90th percentiles. CONCLUSIONS In this population-based cohort we found evidence that working in metal industry was predictive for having elevated blood Pb and Mn concentrations. However, the 95th percentiles of all investigated metals were not significantly influenced by metal-related occupations. The present study is supportive for gender-specific reference values to limit occupational exposure to Mn and Pb. The strong influence of smoking on blood Cd hinders establishing reference values.

How Eye-Preserving Therapy Affects Long-Term Overall Survival in Heritable Retinoblastoma Survivors

PURPOSE Intraocular retinoblastoma is curable, but survivors with a heritable predisposition are at high risk for second malignancies. Because second malignancies are associated with high mortality, prognostic factors for second malignancy influence long-term overall survival. This study investigates the impact of all types of eye-preserving therapies on long-term survival in the complete German cohort of patients with heritable retinoblastoma. PATIENTS AND METHODS Overall survival, disease staging using international scales, time period of diagnosis, and treatment type were analyzed in the 633 German children treated at the national reference center for heritable retinoblastoma. RESULTS The 5-year overall survival of children diagnosed in Germany with heritable retinoblastoma between 1940 and 2008 was 93.2% (95% CI, 91.2% to 95.1%), but long-term mortality was increased compared with patients with nonheritable disease. Overall survival correlated with tumor staging, and 92% of patients were diagnosed with a favorable tumor stage (International Retinoblastoma Staging System stage 0 or I). Despite a 5-year overall survival of 97.4% (95% CI, 96.0% to 98.8%) in patients with stage 0 or I, only 79.5% (95% CI, 74.2% to 84.8%) of these patients survived 40 years after diagnosis. Long-term overall survival was reduced in children treated with eye-preserving radiotherapy compared with enucleation alone, and adding chemotherapy aggravated this effect. CONCLUSION The benefits of preserving vision must be balanced with the impact of eye-preserving treatments on long-term survival in heritable retinoblastoma, and the genetic background of the patient influences choice of eye-preserving treatment. Germline RB1 genetic analysis is important to identify heritable retinoblastoma among unilateral retinoblastoma cases. Eye-preserving radiotherapy should be carefully considered in patients with germline RB1 mutations. Life-long oncologic follow-up is crucial for all retinoblastoma survivors, and less detrimental eye-preserving therapies must be developed.

Is long-term particulate matter and nitrogen dioxide air pollution associated with incident monoclonal gammopathy of undetermined significance (MGUS)? An analysis of the Heinz Nixdorf Recall study

BACKGROUND Exposure to air pollution activates the innate immune system and influences the adaptive immune system in experimental settings. We investigated the association of residential long-term exposure to particulate matter (PM) and NO2 air pollution with monoclonal gammopathy of undetermined significance (MGUS) as a marker of adaptive immune system activation. METHODS We used data from the baseline (2000-2003), 5-year (2006-2008) and 10-year (2011-2015) follow-up examinations of the German Heinz Nixdorf Recall cohort study of 4814 participants (45-75years). Residential exposure to PM size fractions and NO2 was estimated by land-use regression (ESCAPE-LUR, annual mean 2008/2009) and dispersion chemistry transport models (EURAD-CTM, 3-year mean at baseline). We used logistic regression to estimate the effects of air pollutants on incident MGUS, adjusting for age, sex, education, smoking status, physical activity, and BMI. As a non-linear approach, we looked at quartiles (2-4) of the air pollutants in comparison to quartile 1. RESULTS Of the 3949 participants with complete data, 100 developed MGUS during the 10-year follow-up. In the main model, only PMcoarse was associated with incident MGUS (OR per IQR (1.9μg/m3): 1.32, 95% CI 1.04-1.67). We further found positive associations between PM size fractions estimated by ESCAPE-LUR and incident MGUS by quartiles of exposure (OR Q4 vs Q1: PM2.5 2.03 (1.08-3.80); PM10 1.97 (1.05-3.67); PMcoarse 1.98 (1.09-3.60)). CONCLUSIONS Our results indicate that an association between long-term exposure to PM and MGUS may exist. Further epidemiologic studies are needed to corroborate this possible link.

Occupational exposure to manganese and fine motor skills in elderly men: Results from the Heinz Nixdorf Recall Study

Objectives Exposure to manganese (Mn) may cause movement disorders, but less is known whether the effects persist after the termination of exposure. This study investigated the association between former exposure to Mn and fine motor deficits in elderly men from an industrial area with steel production. Methods Data on the occupational history and fine motor tests were obtained from the second follow-up of the prospective Heinz Nixdorf Recall Study (2011-2014). The study population included 1232 men (median age 68 years). Mn in blood (MnB) was determined in archived samples (2000-2003). The association between Mn exposure (working as welder or in other at-risk occupations, cumulative exposure to inhalable Mn, MnB) with various motor functions (errors in line tracing, steadiness, or aiming and tapping hits) was investigated with Poisson and logistic regression, adjusted for iron status and other covariates. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for substantially impaired dexterity (errors >90th percentile, tapping hits <10th percentile). Results The median of cumulative exposure to inhalable Mn was 58 µg m-3 years in 322 men who ever worked in at-risk occupations. Although we observed a partly better motor performance of exposed workers at group level, we found fewer tapping hits in men with cumulative Mn exposure >184.8 µg m-3 years (OR 2.15, 95% CI 1.17-3.94). MnB ≥ 15 µg l-1, serum ferritin ≥ 400 µg l-1, and gamma-glutamyl transferase ≥74 U l-1 were associated with a greater number of errors in line tracing. Conclusions We found evidence that exposure to inhalable Mn may carry a risk for dexterity deficits. Whether these deficits can be exclusively attributed to Mn remains to be elucidated, as airborne Mn is strongly correlated with iron in metal fumes, and high ferritin was also associated with errors in line tracing. Furthermore, hand training effects must be taken into account when testing for fine motor skills.

Agreement of Self-Reported and Administrative Data on Employment Histories in a German Cohort Study: A Sequence Analysis

Collecting life course data is increasingly common in social and epidemiological research, either through record linkage of administrative data or by collecting retrospective interview data. This paper uses data on employment histories collected through both strategies, compares the attained samples, and investigates levels of agreements of individual histories. We use data from the German Heinz Nixdorf Recall Study with information on employment histories collected retrospectively from 2011 until 2014 (N = 3059). Administrative data from the German Institute for Employment Research (IAB) were linked to the survey data. After comparing respondents who provide self-reported histories with the subsample of the ones for which administrative data were available, we investigate the agreement of individual employment histories from the two sources (between 1975 and 2010) using sequence analyses. Almost all participants provided survey data on employment histories (97% of the sample), linkage consent was given by 93%, and administrative data were available for 63% of the participants. People with survey data were more likely to be female, to have a higher education, and to work self-employed and in the tertiary sector. The agreement of individual employment histories is high and similar across time, with a median level of agreement of 89%. Slightly lower values exist for women and people working in the tertiary sector, both having more complex histories. No differences exist for health-related factors. In conclusion, it is likely that missing consent and failed record linkage lead to sample differences; yet, both strategies provide comparable and reliable life course data.