Mapping the Human Exposome to Uncover the Causes of Breast Cancer.

Breast cancer is an important cause of morbidity and mortality for women, yet a significant proportion of variation in individual risk is unexplained. It is reasonable to infer that unexplained breast cancer risks are caused by a myriad of exposures and their interactions with genetic factors. Most epidemiological studies investigating environmental contribution to breast cancer risk have focused on a limited set of exposures and outcomes based on a priori knowledge. We hypothesize that by measuring a rich set of molecular information with omics (e.g., metabolomics and adductomics) and comparing these profiles using a case-control design we can pinpoint novel environmental risk factors. Specifically, exposome-wide association study approaches can be used to compare molecular profiles between controls and either breast cancer cases or participants with phenotypic measures associated with breast cancer (e.g., high breast density, chronic inflammation). Current challenges in annotating compound peaks from biological samples can be addressed by creating libraries of environmental chemicals that are breast cancer relevant using publicly available high throughput exposure and toxicity data, and by mass spectra fragmentation. This line of discovery and innovation will extend understanding of how environmental exposures interact with genetics to affect health, and provide evidence to support new breast cancer prevention strategies

Self-Reported Chemicals Exposure, Beliefs About Disease Causation, and Risk of Breast Cancer in the Cape Cod Breast Cancer and Environment Study: A Case-Control Study

BACKGROUND: Household cleaning and pesticide products may contribute to breast cancer because many contain endocrine disrupting chemicals or mammary gland carcinogens. This population-based case-control study investigated whether use of household cleaners and pesticides increases breast cancer risk. METHODS: Participants were 787 Cape Cod, Massachusetts, women diagnosed with breast cancer between 1988 and 1995 and 721 controls. Telephone interviews asked about product use, beliefs about breast cancer etiology, and established and suspected breast cancer risk factors. To evaluate potential recall bias, we stratified product-use odds ratios by beliefs about whether chemicals and pollutants contribute to breast cancer; we compared these results with odds ratios for family history (which are less subject to recall bias) stratified by beliefs about heredity. RESULTS: Breast cancer risk increased two-fold in the highest compared with lowest quartile of self-reported combined cleaning product use (Adjusted OR = 2.1, 95% CI: 1.4, 3.3) and combined air freshener use (Adjusted OR = 1.9, 95% CI: 1.2, 3.0). Little association was observed with pesticide use. In stratified analyses, cleaning products odds ratios were more elevated among participants who believed pollutants contribute "a lot" to breast cancer and moved towards the null among the other participants. In comparison, the odds ratio for breast cancer and family history was markedly higher among women who believed that heredity contributes "a lot" (OR = 2.6, 95% CI: 1.9, 3.6) and not elevated among others (OR = 0.7, 95% CI: 0.5, 1.1). CONCLUSIONS: Results of this study suggest that cleaning product use contributes to increased breast cancer risk. However, results also highlight the difficulty of distinguishing in retrospective self-report studies between valid associations and the influence of recall bias. Recall bias may influence higher odds ratios for product use among participants who believed that chemicals and pollutants contribute to breast cancer. Alternatively, the influence of experience on beliefs is another explanation, illustrated by the protective odds ratio for family history among women who do not believe heredity contributes "a lot." Because exposure to chemicals from household cleaning products is a biologically plausible cause of breast cancer and avoidable, associations reported here should be further examined prospectively.Massachusetts Legislature; Massachusetts Department of Public Health; Susan S. Bailis Breast Cancer Research Fund at Silent Spring Institute; United States Centers for Disease Control and Prevention (R01 DP000218-01, 1H75EH000377-01

Wrangling environmental exposure data: guidance for getting the best information from your laboratory measurements.

BACKGROUND:Environmental health and exposure researchers can improve the quality and interpretation of their chemical measurement data, avoid spurious results, and improve analytical protocols for new chemicals by closely examining lab and field quality control (QC) data. Reporting QC data along with chemical measurements in biological and environmental samples allows readers to evaluate data quality and appropriate uses of the data (e.g., for comparison to other exposure studies, association with health outcomes, use in regulatory decision-making). However many studies do not adequately describe or interpret QC assessments in publications, leaving readers uncertain about the level of confidence in the reported data. One potential barrier to both QC implementation and reporting is that guidance on how to integrate and interpret QC assessments is often fragmented and difficult to find, with no centralized repository or summary. In addition, existing documents are typically written for regulatory scientists rather than environmental health researchers, who may have little or no experience in analytical chemistry. OBJECTIVES:We discuss approaches for implementing quality assurance/quality control (QA/QC) in environmental exposure measurement projects and describe our process for interpreting QC results and drawing conclusions about data validity. DISCUSSION:Our methods build upon existing guidance and years of practical experience collecting exposure data and analyzing it in collaboration with contract and university laboratories, as well as the Centers for Disease Control and Prevention. With real examples from our data, we demonstrate problems that would not have come to light had we not engaged with our QC data and incorporated field QC samples in our study design. Our approach focuses on descriptive analyses and data visualizations that have been compatible with diverse exposure studies with sample sizes ranging from tens to hundreds of samples. Future work could incorporate additional statistically grounded methods for larger datasets with more QC samples. CONCLUSIONS:This guidance, along with example table shells, graphics, and some sample R code, provides a useful set of tools for getting the best information from valuable environmental exposure datasets and enabling valid comparison and synthesis of exposure data across studies

THERMAL BIOCLIMATE CONDITIONS IN THE ALPINE REGIONS OF AUSTRIA

Data of 46 climate stations located from 1000 m to 3105 m a.s.l. were used to describe the thermal human bioclimate conditions in the alpine regions of Austria. Austria possesses a dense network of climate stations with daily measurements and observations of air temperature, relative humidity, wind velocity and mean cloud cover at 7, 14 and 19 LMT . To show the special climate conditions in alpine regions the behaviour of this parameters in relationship to the human energy balance is used to give a description of the effect of the thermal environment on humans. The importance of topography leading to inversions during the cold seasons and clothing resistance to modify the individual thermal bioclimate will be shown exemplarily

Cell

AbstractPorB of the pathogenic Neisseria species belongs to the large family of pore-forming proteins (porins) produced by gram-negative bacteria. PorB is exceptional in that it is capable of translocating vectorially into membranes of infected target cells and functions in the infection process. Here we report on an unexpected similarity between Neisserial PorB and mitochondrial porins. Both porin classes interact with purine nucleoside triphosphates, which down-regulate pore size and cause a shift in voltage dependence and ion selectivity. Patch-clamp analyses indicate that PorB channel activity is tightly regulated in intact epithelial cells. In light of recent findings on the pivotal role of PorB in virulence and the prevention of phagosome lysosome fusion, these data provide important mechanistic clues on the intracellular pathogen accommodation reminiscent of mitochondrial endosymbiosis

Conserved roles of Sam50 and metaxins in VDAC biogenesis

Voltage-dependent anion-selective channel (VDAC) is a β-barrel protein in the outer mitochondrial membrane that is necessary for metabolite exchange with the cytosol and is proposed to be involved in certain forms of apoptosis. We studied the biogenesis of VDAC in human mitochondria by depleting the components of the mitochondrial import machinery by using RNA interference. Here, we show the importance of the translocase of the outer mitochondrial membrane (TOM) complex in the import of the VDAC precursor. The deletion of Sam50, the central component of the sorting and assembly machinery (SAM), led to both a strong defect in the assembly of VDAC and a reduction in the steady-state level of VDAC. Metaxin 2-depleted mitochondria had reduced levels of metaxin 1 and were deficient in import and assembly of VDAC and Tom40, but not of three matrix-targeted precursors. We also observed a reduction in the levels of metaxin 1 and metaxin 2 in Sam50-depleted mitochondria, implying a connection between these three proteins, although Sam50 and metaxins seemed to be in different complexes. We conclude that the pathway of VDAC biogenesis in human mitochondria involves the TOM complex, Sam50 and metaxins, and that it is evolutionarily conserved

Arriving at Wheat Marketing Decisions

This focus of this bulletin is on various facets of wheat marketing, including historic market information, current market information, and a basic wheat marketing information