Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene–environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4×10−6) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1×10−4). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01–1.16) in nulliparous women and ranged from 1.03 (0.96–1.10) in parous women with one birth to 1.26 (1.16–1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85–0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14–1.85) in those who drank ≥20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3×10−5), with a per-allele OR of 1.14 (1.11–1.17) in parous women and 0.98 (0.92–1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

ning 11 and The Weldox GroupWe investigated airborne and internal exposure to manganese (Mn) and iron (Fe) among welders. Personal sampling of welding fumes was carried out in 241 welders during a shift. Metals were determined by inductively coupled plasma mass spectrometry. Mn in blood (MnB) was analyzed by graphite furnace atom absorption spectrometry. Determinants of exposure levels were estimated with multiple regression models. Respirable Mn was measured with a median of 62 (inter-quartile range (IQR) 8.4 --320) mg/m 3 and correlated with Fe (r ¼ 0.92, 95% CI 0.90 --0.94). Inhalable Mn was measured with similar concentrations (IQR 10 --340 mg/m 3 ). About 70% of the variance of Mn and Fe could be explained, mainly by the welding process. Ventilation decreased exposure to Fe and Mn significantly. Median concentrations of MnB and serum ferritin (SF) were 10.30 mg/l (IQR 8.33 --13.15 mg/l) and 131 mg/l (IQR 76 --240 mg/l), respectively. Few welders were presented with low iron stores, and MnB and SF were not correlated (r ¼ 0.07, 95% CI À0.05 to 0.20). Regression models revealed a significant association of the parent metal with MnB and SF, but a low fraction of variance was explained by exposure-related factors. Mn is mainly respirable in welding fumes. Airborne Mn and Fe influenced MnB and SF, respectively, in welders. This indicates an effect on the biological regulation of both metals. Mn and Fe were strongly correlated, whereas MnB and SF were not, likely due to higher iron stores among welders.

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PurposeSystemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that can affect the central nervous system. Neuropsychiatric symptoms are found in 25–70% of patients. Using diffusion tensor imaging (DTI) various studies have reported changes in white matter integrity in SLE patients with neuropsychiatric symptoms (NPSLE patients). The purpose of this study was to investigate, if regional changes in white matter integrity can also be detected in SLE patients without neuropsychiatric symptoms (non-NPSLE patients).MethodsApplying DTI and tract based spatial statistics (TBSS) we investigated 19 NPSLE patients, 19 non-NPSLE and 18 healthy controls. Groups were matched for age and sex. Image pre-processing was performed using FSL, following the TBSS pipeline (eddy current correction, estimation of fractional anisotropy (FA), normalization, skeletonization of the group mean FA image). A general linear model with threshold-free cluster enhancement was used to assess significant differences between the three groups.ResultsStatistical analyses revealed several regions of decreased prefrontal white matter integrity (decreased FA) in both groups of SLE patients. The changes found in the non-NPSLE patients (as compared to healthy controls) overlapped with those in the NPSLE patients, but were not as pronounced.ConclusionsOur data suggest that changes in regional white matter integrity, in terms of a decrease in FA, are present not only in NPSLE patients, but also in non-NPSLE patients, though to a lesser degree. We also demonstrate that the way statistical maps are corrected for multiple comparisons has a profound influence on whether alterations in white matter integrity in non-NPSLE patients are deemed significant.

In conclusion, the results of our population-based case-control study support a putative role of the CLOCK gene in the development of breast cancer in shift workers. In addition, higher order interaction analyses suggest a potential relevance of MTNR1B with the key transcriptional factor NPAS2 with ARNTL. Hence, in the context of circadian disruption, multivariable models should be preferred that consider a wide range of polymorphisms, e.g. that may influence chronotype or light sensitivity. The investigation of these interactions in larger studies is needed.

This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m−3 for inhalable and 1.29 mg m−3 for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m−3). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements

Indoor allergens are among the main causes of allergic rhinitis and asthma. Allergen exposure is not limited to private homes. Mite, cat, and dog allergens were measured in day care centers to determine whether these concentrations detected might exert significant influence on human health. In 20 day care centers across North Rhine-Westphalia, Germany, the surfaces of 171 rooms were vacuumed 4 times a year to collect dust (1340 samples in total). In all samples, domestic mite antigens (DM) and the main allergens of cats (Fel d 1) and dogs (Can f 1) were quantified using enzyme immunoassays. Provisional threshold limits (PTL) for increased risks of sensitization and allergic symptoms were estimated according to published values and conversion factors. The influence of room characteristics on allergen concentrations was analyzed in mixed linear models, also considering values below the limit of detection (LOD). Nearly all samples contained allergens (99% DM, 96% Fel d 1, and 96% Can f 1). The concentrations rarely exceeded levels that were previously found to induce symptoms in home environments, but were frequently higher than estimates for enhanced sensitization risk (13% DM, 43% Fel d 1, and 27% Can f 1). Upholstered furnishings had the highest dust and allergen loads, followed by carpets and smooth floors. Allergen concentrations on different surface types that were sampled in the same room at the same time were significantly correlated and analyzed in separate models. The highest DM concentrations were present in bedrooms and in autumn. Further, DM loads on floors decreased significantly in rooms that were renovated within the last 5 years. If there were no records that furnishings were vacuumed, there were then significantly higher Can f 1 loads. Sweeping floors elevated DM and cat allergen concentrations. In addition to mite allergens, cat and dog allergens were detected in nearly all samples from day care centers. Overall, the present results indicate that allergen concentrations may be reduced by renovation and appropriate cleaning procedures.

GENICA is a population-based case-control study on breast cancer with detailed information on shift work characteristics. We are the first to show the associations between night shift work and breast cancer with respect to estrogen receptor (ER) positive and negative tumors. Our results suggest a stronger association of chronobiological mechanisms with the development of ER-negative breast cancers. Original article Scand J Work Environ Health. 2013;39(5):448-455. doi:10.5271/sjweh.3360 Night work and breast cancer estrogen receptor status -results from the German GENICA study Objectives The potential mechanisms that link night-shift work with breast cancer have been extensively discussed. Exposure to light at night (LAN) depletes melatonin that has oncostatic and anti-estrogenic properties and may lead to a modified expression of estrogen receptor (ER) α. Here, we explored the association between shift work and breast cancer in subgroups of patients with ER-positive and -negative tumors. AffiliationMethods GENICA (Gene-ENvironment Interaction and breast CAncer) is a population-based case-control study on breast cancer with detailed information on shift work from 857 breast cancer cases and 892 controls. ER status was assessed by immunohistochemical staining. Associations between night-shift work and ER-positive and -negative breast cancer were analyzed with conditional logistic regression models, adjusted for potential confounders.Results ER status was assessed for 827 cases and was positive in 653 and negative in 174 breast tumors.Overall, 49 cases and 54 controls were "ever employed" in shift work including night shifts for ≥1 year. In total, "ever shift work" and "ever night work" were not associated with an elevated risk of ER-positive or -negative breast tumors. Night work for ≥20 years was associated with a significantly elevated risk of ER-negative breast cancer [odds ratio (OR) 4.73, 95% confidence interval (95% CI) 1.22-18.36].Conclusions Our case-control study suggests that long-term night-shift work is associated with an increased risk of ER-negative breast cancers. Further studies on histological subtypes and the analysis of other potentially relevant factors are crucial for discovering putative mechanisms.