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There is accumulating evidence that high levels of dietary iron may play a role in colon carcinogenesis. We used a mouse model to investigate the impact of elevated dietary iron on incidence of aberrant crypt foci (ACF : a preneoplastic lesion) on tumor formation and on induction of oxidative stress. A/J mice were injected intraperitoneally, once a week for 6 weeks, with the colontropic carcinogen, azoxymethane (AOM) or saline (vehicle controls). Following AOM or saline treatments, mice were placed on diets of high (3,000 ppm) and low (30 ppm) iron. Mice in each treatment group were sacrificed at 6 and 10 weeks following the final injection with AOM or saline. Colons were removed for subsequent histopathological analysis, which revealed average increases of 4.6 ± 1.3 vs. 10.4 ± 2.5 total tumors at 6 weeks and 30.75 ± 2.7 vs. 41.5 ± 4.4 total tumors at 10 weeks per AOM-treated mouse on low- and high-iron diets, respectively. There were no significant differences in incidence of ACF attributable to iron, although there was a trend toward greater crypt multiplicity per focus in mice on high-iron diets. Notably, no tumors were observed in mice receiving vehicle control injections in place of carcinogen, regardless of the level of dietary iron. These data suggest that iron exerts its effect at the stage of tumor promotion, but is not sufficient to initiate tumor formation. To learn more about mechanisms by which iron promotes tumor growth, colons were assayed for several biomarkers of oxidative stress [BOS : total F2-isoprostanes (F2-IsoPs), 15-F2t-isoprostanes (8-IsoPGF2[alpha]s), Isofurans (IsoFs), and 8-hydroxyguanosines (8-OH[d]Gs)], as well as iron absorption, programmed cell death, and cellular proliferation. Elevated PCNA and TUNEL staining of the colon epithelium revealed hyperproliferative and apoptotic responses to iron, while no significant differences between iron groups were observed in each of the BOS that were assayed. Our results suggest that, following carcinogen exposure, elevated dietary iron promotes the growth of tumors with altered cellular homeostasis through a mechanism that is independent of oxidative stress. [ABSTRACT FROM AUTHOR]

BRCA1 and BRCA2 genes are involved in DNA double-strand break repair and related to breast cancer. Shift work is associated with biological clock alterations and with a higher risk of breast cancer. The aim of this study was to investigate the variability of expression of BRCA genes through the day in healthy subjects and to measure BRCA expression levels in shift workers. The study was approached in two ways. First, we examined diurnal variation of BRCA1 and BRCA2 genes in lymphocytes of 15 volunteers over a 24-hour period. Second, we measured the expression of these genes in lymphocytes from a group of shift and daytime workers. The change in 24-hour expression levels of BRCA1 and BRCA2 genes was statistically significant, decreasing from the peak at midday to the lowest level at midnight. Lower levels for both genes were found in shift workers compared to daytime workers. Diurnal variability of BRCA1 and BRCA2 expression suggests a relation of DNA double-strand break repair system with biological clock. Lower levels of BRCA1 and BRCA2 found in shift workers may be one of the potential factors related to the higher risk of breast cancer., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Background: Clostridium difficile is a gram-positive, anaerobic, and spore-forming bacillus, which is responsible for the majority of antibiotic-associated diarrhea and colitis., Objective: Determine if fecal microbiota transplantation (FMT) is effective in a population sample from Connecticut., Methods: We report the clinical experience of 92 consecutive patients from one gastroenterology practice in central Connecticut treated by colonoscopy with FMT for infection with Clostridium difficile from 2012 to 2017. The analyses are based on clinical follow-up up to 3 months after the FMT procedure and on medical chart review., Results: Overall, complete recovery occurred in 86% of patients. As previously reported in a limited number of previous studies, community-acquired cases were more common than hospital-acquired cases, and community-acquired cases were more likely to be female., Conclusions: Consistent with some previous reports, we found the following: the source of the donor for FMT did not make a difference in recovery: material from nonrelatives was as effective as from close relatives; and the presence of multiple comorbidities did not make a difference in recovery: patients with 2 or more comorbidities did as well as those with one or none., (© 2019 S. Karger AG, Basel.)

Breast cancer (BC) incidence rates in Connecticut are among the highest in the United States, and are unevenly distributed within the state. Our goal was to determine whether artificial light at night (ALAN) played a role. Using BC records obtained from the Connecticut Tumor Registry, we applied the double kernel density (DKD) estimator to produce a continuous relative risk surface of a disease throughout the State. A multi-variate analysis compared DKD and census track estimates with population density, fertility rate, percent of non-white population, population below poverty level, and ALAN levels. The analysis identified a "halo" geographic pattern of BC incidence, with the highest rates of the disease observed at distances 5-15 km from the state's major cities. The "halo" was of high-income communities, with high ALAN, located in suburban fringes of the state's main cities., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Ascorbate redox metabolism and growth have been shown to be linked and related to the activity of enzymes that produce or remove the radical monodehydroascorbate, the semi-oxidized form of ascorbate (ascorbate oxidase or peroxidase and monodehydroascorbate reductase respectively). Previous work in cherry tomato has revealed correlations between monodehydroascorbate reductase and ascorbate oxidase activity and fruit yield: decreased whole plant MDHAR activity decreases yield while decreased whole plant ascorbate oxidase activity increases yield under unfavourable environmental conditions. We aimed to investigate if similar effects on yield are obtained in a large-fruited variety of tomato, Moneymaker. Furthermore we wished to establish whether previously observed effects on yield in cherry tomato following changes in whole plant enzyme activity could be reproduced by reducing MDHAR activity in fruit only by using a fruit-specific promoter in cherry tomato (West Virginia 106). In Moneymaker, RNAi lines for monodehydroascorbate reductase did not show significant yield decrease compared to control lines when plants were grown under optimal or non-optimal conditions of carbon stress generated by mature leaf removal. In addition, we show that a decrease in monodehydroascorbate reductase activity in fruit of cherry tomato had no effect on yield compared to a reduction in whole-plant monodehydroascorbate reductase activity: we therefore show that whole plant MDHAR activity is necessary to maintain yield in cherry tomato, suggesting that the carbon source in autotrophic tissue is more important than fruit sink activity. The present data also revealed differences between cherry and large fruited tomato that could be linked to a source of genetic variability in the response to monodehydroascorbate metabolism in tomato: maybe the domestication of tomato towards large-fruited lines could have affected the importance of MDHAR in yield maintenance., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion found within the human colon. Despite their relatively high frequency in the distal colon, few studies have examined the molecular characteristics of ACF within the proximal colon. In the following study, clinical participants ( n = 184) were screened for ACF using high-definition chromoendoscopy with contrast dye-spray. Following pathologic confirmation, ACF biopsies were subjected to laser capture microdissection (LCM), and epithelial cells were evaluated for somatic mutations with a customized colorectal cancer mutation panel using DNA-mass spectrometry. Samples were further characterized for microsatellite instability (MSI). Logistic models were used to associate proximal ACF with synchronous (detected during the same procedure) neoplasia. Thirty-nine percent of participants had at least one histologically confirmed proximal ACF. Individuals with a proximal ACF were significantly more likely to present with a synchronous neoplasm ( P = 0.001), and specifically, a proximal, tubular, or tubulovillous adenoma (multivariable OR = 2.69; 95% confidence interval, 1.12-6.47; P = 0.027). Proximal ACF were more likely to be dysplastic (52%) compared with distal ACF (13%; P < 0.0001). Somatic mutations to APC, BRAF, KRAS, NRAS , and ERBB2 were detected in 37% of proximal ACF. Hyperplastic ACF were more often MSI-high, but there were no differences in MSI status observed by colonic location. In summary, ACF are identified in the proximal colons of approximately 40% of individuals undergoing chromoendoscopy and more often in patients with synchronous proximal adenomas. Implications: This study provides the most complete set of data, to date, that ACF represent the earliest step in the adenoma-carcinoma sequence but remain below the detection limit of conventional endoscopy. Visual Overview: http//mcr.accrjournals.org/content/molcanres/16/3/486/F1.large.jpg Mol Cancer Res; 16(3); 486-95. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Changing the balance between ascorbate, monodehydroascorbate, and dehydroascorbate in plant cells by manipulating the activity of enzymes involved in ascorbate synthesis or recycling of oxidized and reduced forms leads to multiple phenotypes. A systems biology approach including network analysis of the transcriptome, proteome and metabolites of RNAi lines for ascorbate oxidase, monodehydroascorbate reductase and galactonolactone dehydrogenase has been carried out in orange fruit pericarp of tomato ( Solanum lycopersicum ). The transcriptome of the RNAi ascorbate oxidase lines is inversed compared to the monodehydroascorbate reductase and galactonolactone dehydrogenase lines. Differentially expressed genes are involved in ribosome biogenesis and translation. This transcriptome inversion is also seen in response to different stresses in Arabidopsis. The transcriptome response is not well correlated with the proteome which, with the metabolites, are correlated to the activity of the ascorbate redox enzymes-ascorbate oxidase and monodehydroascorbate reductase. Differentially accumulated proteins include metacaspase, protein disulphide isomerase, chaperone DnaK and carbonic anhydrase and the metabolites chlorogenic acid, dehydroascorbate and alanine. The hub genes identified from the network analysis are involved in signaling, the heat-shock response and ribosome biogenesis. The results from this study therefore reveal one or several putative signals from the ascorbate pool which modify the transcriptional response and elements downstream.

Purpose: Ionizing radiation and high levels of circulating estradiol are known breast cancer carcinogens. We investigated the risk of first primary postmenopausal breast cancer in relation to the combined effects of whole-body ionizing radiation exposure and prediagnostic levels of postmenopausal sex hormones, particularly bioavailable estradiol (bE 2 )., Materials and Methods: A nested case-control study of 57 incident breast cancer cases matched with 110 controls among atomic bomb survivors. Joint effects of breast radiation dose and circulating levels of sex hormones were assessed using binary regression and path analysis., Results and Conclusion: Radiation exposure, higher levels of bE 2 , testosterone and progesterone, and established reproductive risk factors were positively associated with postmenopausal breast cancer risk. A test for mediation of the effect of radiation via bE 2 level suggested a small (14%) but significant mediation (p = 0.004). The estimated interaction between radiation and bE 2 was large but not significant (interaction = 3.86; p = 0.32). There is accumulating evidence that ionizing radiation not only damages DNA but also alters other organ systems. While caution is needed, some portion of the radiation risk of postmenopausal breast cancer appeared to be mediated through bE 2 levels, which may be evidence for cancer risks due to both direct and indirect effects of radiation.

The invention of electric light has facilitated a society in which people work, sleep, eat, and play at all hours of the 24-hour day. Although electric light clearly has benefited humankind, exposures to electric light, especially light at night (LAN), may disrupt sleep and biological processes controlled by endogenous circadian clocks, potentially resulting in adverse health outcomes. Many of the studies evaluating adverse health effects have been conducted among night- and rotating-shift workers, because this scenario gives rise to significant exposure to LAN. Because of the complexity of this topic, the National Toxicology Program convened an expert panel at a public workshop entitled "Shift Work at Night, Artificial Light at Night, and Circadian Disruption" to obtain input on conducting literature-based health hazard assessments and to identify data gaps and research needs. The Panel suggested describing light both as a direct effector of endogenous circadian clocks and rhythms and as an enabler of additional activities or behaviors that may lead to circadian disruption, such as night-shift work and atypical and inconsistent sleep-wake patterns that can lead to social jet lag. Future studies should more comprehensively characterize and measure the relevant light-related exposures and link these exposures to both time-independent biomarkers of circadian disruption and biomarkers of adverse health outcomes. This information should lead to improvements in human epidemiological and animal or in vitro models, more rigorous health hazard assessments, and intervention strategies to minimize the occurrence of adverse health outcomes due to these exposures., (Published by Elsevier B.V.)

In 2007, the International Agency for Research on Cancer declared shift work that involved circadian disruption to be a "probable" carcinogen (group 2A), noting that human evidence was limited. Using data from 2 prospective cohort studies, the Nurses' Health Study (1988-2012; n = 78,516) and Nurses' Health Study II (1989-2013; n = 114,559), we examined associations between rotating night-shift work and breast cancer risk. In the 2 cohorts, there were a total of 9,541 incident invasive breast malignancies and 24 years of follow-up. In the Nurses' Health Study, women with 30 years or more of shift work did not have a higher risk of breast cancer (hazard ratio (HR) = 0.95, 95% confidence interval (95% CI): 0.77, 1.17; P for trend = 0.63) compared with those who never did shift work, although follow-up occurred primarily after retirement from shift work. Among participants in the Nurses' Health Study II, who were younger than participants in the other cohort, the risk of breast cancer was significantly higher in women with 20 years or more of shift work at baseline, reflecting young-adult exposure (HR = 2.15, 95% CI: 1.23, 3.73; P for trend = 0.23), and was marginally significantly higher for women with 20 years or more of cumulative shift work when we used updated exposure information (HR = 1.40, 95% CI: 1.00, 1.97; P for trend = 0.74). In conclusion, long-term rotating night-shift work was associated with a higher risk of breast cancer, particularly among women who performed shift work during young adulthood. Further studies should explore the role of shift work timing on breast cancer risk., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

IN BRIEF Several contraindications limit the use of metformin, most notably the risk of lactic acidosis. This article reports on an examination of a population of patients with diabetes with preserved renal function to evaluate provider compliance with guidelines on metformin use and to identify factors that contributed when practice diverged from recommendations. It found that metformin was withheld from approximately one-third of these patients because of 1 ) an existent contraindication to metformin, 2 ) patient behavior or preference, or 3 ) provider preference or bias based on patient or personal factors. Although providers generally follow current recommendations for the use of metformin, deviations from guidelines in practice are common.

Ascorbate content in plants is controlled by its synthesis from carbohydrates, recycling of the oxidized forms and degradation. Of these pathways, ascorbate degradation is the least studied and represents a lack of knowledge that could impair improvement of ascorbate content in fruits and vegetables as degradation is non-reversible and leads to a depletion of the ascorbate pool. The present study revealed the nature of degradation products using [ 14 C]ascorbate labelling in tomato, a model plant for fleshy fruits; oxalate and threonate are accumulated in leaves, as is oxalyl threonate. Carboxypentonates coming from diketogulonate degradation were detected in relatively insoluble (cell wall-rich) leaf material. No [ 14 C]tartaric acid was found in tomato leaves. Ascorbate degradation was stimulated by darkness, and the degradation rate was evaluated at 63% of the ascorbate pool per day, a percentage that was constant and independent of the initial ascorbate or dehydroascorbic acid concentration over periods of 24 h or more. Furthermore, degradation could be partially affected by the ascorbate recycling pathway, as lines under-expressing monodehydroascorbate reductase showed a slight decrease in degradation product accumulation., (© 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.)

Objectives: To examine the underlying mechanisms through which steady state emotions, specifically affect and emotion regulation, influence sleep quality among young adult low-income women., Design: Cross-sectional., Setting: Stress and Health Study (2006-2012) in southeast Texas., Participants: A subgroup (n=392) of racially and ethnically diverse young adult women ages 18-31., Measurements: Participants provided measures of positive and negative affect, difficulties in emotion regulation, and sleep quality. Structural equation models were designed to identify differential mediating roles of emotion dysregulation in the association between both positive and negative affect and sleep quality., Results: The relationship between positive affect and improved sleep quality operated completely through domains of emotion regulation (β= -0.054, 95% CI: -0.08 to -0.03), whereas the adverse effects of negative affect exhibited both direct (β= 0.142, 95% CI: 0.06 to 0.23) and indirect (β= 0.124, 95% CI: 0.08 to 0.16) effects on poor sleep. Negative affect was associated with poor sleep quality via two pathways-it directly influenced sleep quality and it indirectly influenced sleep quality among women experiencing difficulties in emotion regulation., Conclusions: Therapies targeting improvement and maintenance of healthy emotion regulation domains, while delineating the positive affect state from the negative affect state, may lessen the burden of poor sleep quality among low-income women.

The aim of this study was to test the prediction that within the state of Connecticut, USA, communities with high nighttime outdoor light level would have higher breast cancer incidence rates. Breast cancer cases were identified from the Connecticut Tumor Registry, the oldest within the United States, for years 2005 and 2009 and geocoded to the 829 census tracts in the state. Nighttime light level (LAN) was obtained from the Defense Meteorological Satellite Program (DMSP), 1996/97 satellite image, providing a 10-year lag. Regression models were used incorporating the LAN levels and census level data on potential confounders for the whole female population of the state, and for separate age groups. Light level emerged as a significant predictor of breast cancer incidence. After taking account of several potential confounders, the excess risk in the highest LAN level census tracts compared to the lowest was about 63% (RR=1.63; 95% CI=1.41, 1.89). The association of LAN with breast cancer incidence weakened with age; the association was strongest among premenopausal women., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Ascorbate is oxidized into the radical monodehydroascorbate (MDHA) through ascorbate oxidase or peroxidase activity or non-enzymatically by reactive oxygen species. Regeneration of ascorbate from MDHA is ensured by the enzyme MDHA reductase (MDHAR). Previous work has shown that growth processes and yield can be altered by modifying the activity of enzymes that recycle ascorbate; therefore, we have studied similar processes in cherry tomato (Solanum lycopersium L.) under- or overexpressing MDHAR. Physiological and metabolic characterization of these lines was carried out under different light conditions or by manipulating the source-sink ratio. Independently of the light regime, slower early growth of all organs was observed in MDHAR silenced lines, decreasing final fruit yield. Photosynthesis was altered as was the accumulation of hexoses and sucrose in a light-dependent manner in plantlets. Sucrose accumulation was also repressed in young fruits and final yield of MDHAR silenced lines showed a stronger decrease under carbon limitation, and the phenotype was partially restored by reducing fruit load. Ascorbate and MDHA appear to be involved in control of growth and sugar metabolism in cherry tomato and the associated enzymes could be potential targets for yield improvement., (© 2016 John Wiley & Sons Ltd.)

Purpose: A comparatively high prevalence of comorbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients., Methods: We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors., Results: Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74-3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90-11.02). A lower and nonsignificant effect was observed for whites with a CCI of ≥3 (Adj. HR 1.90, 95 % CI 0.68-5.29)., Conclusions: comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk.

Purpose: Based on suggestive findings from a recent study of high-risk Japanese patients, we sought to determine whether the risk of colorectal polyps associated with smoking may be modified by daily use of aspirin in an analysis of a large US screening population., Methods: This is a cross-sectional study of 2,918 consecutive colonoscopy patients at a university hospital over a 30-month period. Data were abstracted from electronic medical records. Multivariate models of polyp counts were used to examine the competing risks of smoking and aspirin use. Models were further stratified by polyp location (proximal vs. distal) and pathologic subtype (dysplastic vs. serrated)., Results: Incidental rate of polyps was higher among active smokers [incidence rate ratio (IRR) 1.72; 95 % confidence interval (CI) 1.46-2.02] and lower among daily aspirin users (IRR 0.73; 95 % CI 0.61-0.86) compared to those who used neither. Smoking interacts significantly with aspirin use resulting in loss of aspirin protection (IRR 1.69; 95 % CI 1.28-2.24). Stratified analyses demonstrate that aspirin specifically reduces the risk of traditional dysplastic adenomas (IRR 0.72; 95 % CI 0.61-0.86) not serrated/hyperplastic polyps (IRR 0.92; 95 % CI 0.72-1.17) and that the modification of aspirin protection by smoking is primarily observed within the distal colorectum (p < 0.03)., Conclusions: We report for the first time, in a typical risk US clinical population, a lack of protective association of aspirin for polyps among active smokers. Future prospective studies are recommended to confirm this mitigating effect in order to improve the precision of the growing evidence base about the chemopreventive benefit of aspirin in colorectal cancer.

Electric light is one of the signature inventions of human beings. A problem, however, is that electric light can confuse our endogenous circadian rhythmicity. It has now become apparent that circadian biology is fundamental to the functioning and adaptation of almost all life forms. In the modern world, everyone is exposed to electric light during the day and night, and thereby can experience some level of circadian disruption. Perhaps as a canary in the coal mine, study of people whose work hours include nighttime (shift workers) is beginning to yield insights on the adverse health effects of circadian disruption from electric light.

The DNA base excision repair pathway is the main system involved in the removal of oxidative damage to DNA such as 8-Oxoguanine (8-oxoG) primarily via the 8-Oxoguanine DNA glycosylase (OGG1). Our goal was to investigate whether the repair of 8-oxoG DNA damage follow a circadian rhythm. In a group of 15 healthy volunteers, we found a daily variation of Ogg1 expression and activity with higher levels in the morning compared to the evening hours. Consistent with this, we also found lower levels of 8-oxoG in morning hours compared to those in the evening hours. Lymphocytes exposed to oxidative damage to DNA at 8:00 AM display lower accumulation of 8-oxoG than lymphocytes exposed at 8:00 PM. Furthermore, altered levels of Ogg1 expression were also observed in a group of shift workers experiencing a deregulation of circadian clock genes compared to a control group. Moreover, BMAL1 knockdown fibroblasts with a deregulated molecular clock showed an abolishment of circadian variation of Ogg1 expression and an increase of OGG1 activity. Our results suggest that the circadian modulation of 8-oxoG DNA damage repair, according to a variation of Ogg1 expression, could render humans less susceptible to accumulate 8-oxoG DNA damage in the morning hours.

Study Objectives: To document the time course of perceived stress among women through the period of a natural disaster, to determine the effect of sleep quality on this time course, and to identify risk factors that predict higher levels of perceived stress., Design: Longitudinal study from 2006-2012., Setting: Community-based family planning clinics in southeast Texas., Participants: There were 296 women aged 18-31 y who experienced Hurricane Ike, September 2008., Measurements and Results: Cohen Perceived Stress Scale (PSS) was administered every 2 mo from 6 mo before to 12 mo after Hurricane Ike. Sleep quality was assessed 1 mo after Hurricane Ike using the Pittsburg Sleep Quality Index (PSQI). Good sleep was defined as a PSQI summary score < 5, and poor sleep as a score ≥ 5. Hurricane Ike stressors (e.g., property damage, subjective stressors) and pre-Ike lifetime major life events and emotional health (e.g., emotional dysregulation, self-control) were also assessed., Results: Over the entire period of 18 mo (6 mo before and 12 mo after the hurricane), perceived stress was significantly higher among poor sleepers compared to good sleepers, and only good sleepers showed a significant decrease in perceived stress after Hurricane Ike. In addition, a higher level of perceived stress was positively associated with greater Ike damage among poor sleepers, whereas this correlation was not observed among good sleepers. In the final multivariate longitudinal model, Ike-related subjective stressors as well as baseline major life events and emotional dysregulation among poor sleepers predicted higher levels of perceived stress over time; among good sleepers, additional factors such as lower levels of self-control and having a history of a psychiatric disorder also predicted higher levels of perceived stress., Conclusions: Sleep quality after Hurricane Ike, an intense natural disaster producing substantial damage, impacted changes in perceived stress over time. Our findings suggest the possibility that providing victims of disasters with effective interventions to improve sleep quality could help to reduce their perceived stress over time., (© 2015 Associated Professional Sleep Societies, LLC.)

Over the past 3 billion years, an endogenous circadian rhythmicity has developed in almost all life forms in which daily oscillations in physiology occur. This allows for anticipation of sunrise and sunset. This physiological rhythmicity is kept at precisely 24 h by the daily cycle of sunlight and dark. However, since the introduction of electric lighting, there has been inadequate light during the day inside buildings for a robust resetting of the human endogenous circadian rhythmicity, and too much light at night for a true dark to be detected; this results in circadian disruption and alters sleep/wake cycle, core body temperature, hormone regulation and release, and patterns of gene expression throughout the body. The question is the extent to which circadian disruption compromises human health, and can account for a portion of the modern pandemics of breast and prostate cancers, obesity, diabetes and depression. As societies modernize (i.e. electrify) these conditions increase in prevalence. There are a number of promising leads on putative mechanisms, and epidemiological findings supporting an aetiologic role for electric lighting in disease causation. These include melatonin suppression, circadian gene expression, and connection of circadian rhythmicity to metabolism in part affected by haem iron intake and distribution., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)

Purpose: Given the relatively high prevalence of sickle cell trait and disease among African Americans and established racial disparities in cancer outcomes, we reviewed the literature regarding adverse events in cancer patients with these hematologic genotypes. Erythrocyte sickling can result from extreme hypoxia and other physiologic stressors, as might occur during cancer therapy. Further, tumoral hypoxia, a poor prognostic and predictive factor, could lead to a cycle of local sickling and increased hypoxia., Methods: A search of PubMed produced 150 publications, most of which were excluded because of incidental relevance. Eleven case reports of patients diagnosed from 1993 to 2013 were reviewed., Results: Two reports of patients with sickle cell trait describe an abundance of sickled erythrocytes within tumors, and a third report describes sickling-related events requiring multiday hospitalization. Eight reports of patients with sickle cell disease delineated multiorgan failure, vaso-occlusive crises, and rapid renal deterioration. Hypothesized triggers are delayed clearance of anticancer agents attributable to baseline kidney damage, activation of vasoadherent neutrophils from treatment to counter chemotherapy-induced neutropenia, hypoxia from general anesthesia, and intratumoral hypoxia., Conclusion: Clinical implications include pretreatment genotyping for prophylaxis, dose adjustment, and enhanced patient monitoring. With the current lack of high-quality evidence, however, the scope of poor outcomes remains unknown.

Purpose: Although the evidence linking exposure to light at night (LAN) and breast cancer risk continues to accumulate, the molecular mechanisms driving this association remain to be fully elucidated. We have previously suggested that long-term exposure to LAN through shiftwork may result in dysregulated patterns of methylation genome-wide. In this study, we investigate the link between miR-34b, a miRNA suggested to be an important tumor suppressor, and shiftwork-related breast cancer., Methods: Methylation states in the miR-34b promoter region were previously compared between 10 female long-term shiftworkers and 10 folate intake- and age-matched female dayworkers participating in the Danish "Diet, Cancer and Health" prospective cohort study. In order to further explore the functional role of miR-34b in breast tumorigenesis, a genome-wide expression microarray was carried out in miR-34b-overexpressed MCF-7 breast cancer cells and the identified transcripts were further analyzed for network and functional interrelatedness using Ingenuity Pathway Analysis software., Results: We observed a 49.1 % increase in miR-34b promoter methylation among shiftworkers at a CpG site in this region (p = 0.016). Transfection of the miR-34b mimic in an MCF-7 breast cancer cell line induced differential expression of 230 transcripts that are involved in the interferon-mediated antiviral response as well as apoptotic and antiproliferative gene networks., Conclusions: Together, our results suggest that long-term shiftwork may increase the risk of breast cancer via methylation-based suppression of miR-34b and a consequent reduction in immunomediated anti-tumor capacity and support our previous findings that LAN may induce epigenetic alteration of cancer-relevant microRNAs.

Disruptions in iron homeostasis are linked to a broad spectrum of chronic conditions including cardiovascular, malignant, metabolic, and neurodegenerative disease. Evidence supporting this contention derives from a variety of analytical approaches, ranging from molecular to population-based studies. This review focuses on key epidemiological studies that assess the relationship between body iron status and chronic diseases, with particular emphasis on atherosclerosis ,metabolic syndrome and diabetes. Multiple surrogates have been used to measure body iron status, including serum ferritin, transferrin saturation, serum iron, and dietary iron intake. The lack of a uniform and standardized means of assessing body iron status has limited the precision of epidemiological associations. Intervention studies using depletion of iron to alter risk have been conducted. Genetic and molecular techniques have helped to explicate the biochemistry of iron metabolism at the molecular level. Plausible explanations for how iron contributes to the pathogenesis of these chronic diseases are beginning to be elucidated. Most evidence supports the hypothesis that excess iron contributes to chronic disease by fostering excess production of free radicals. Overall, epidemiological studies, reinforced by basic science experiments, provide a strong line of evidence supporting the association between iron and elevated risk of cardiovascular disease and diabetes. In this narrative review we attempt to condense the information from existing literature on this topic.

Breast cancer is the leading cause of cancer death among women worldwide, and there is only a limited explanation of why. Risk is highest in the most industrialized countries but also is rising rapidly in the developing world. Known risk factors account for only a portion of the incidence in the high-risk populations, and there has been considerable speculation and many false leads on other possibly major determinants of risk, such as dietary fat. A hallmark of industrialization is the increasing use of electricity to light the night, both within the home and without. It has only recently become clear that this evolutionarily new and, thereby, unnatural exposure can disrupt human circadian rhythmicity, of which three salient features are melatonin production, sleep, and the circadian clock. A convergence of research in cells, rodents, and humans suggests that the health consequences of circadian disruption may be substantial. An innovative experimental model has shown that light at night markedly increases the growth of human breast cancer xenografts in rats. In humans, the theory that light exposure at night increases breast cancer risk leads to specific predictions that are being tested epidemiologically: evidence has accumulated on risk in shift workers, risk in blind women, and the impact of sleep duration on risk. If electric light at night does explain a portion of the breast cancer burden, then there are practical interventions that can be implemented, including more selective use of light and the adoption of recent advances in lighting technology and application., (© 2013 American Cancer Society, Inc.)

Several prospective studies suggest that C-reactive protein (CRP), a nonspecific serologic marker of inflammation, might be linked to risk of colorectal cancer (CRC), whereas others have reported null or protective effects. We analyzed data from 7,072 participants (50-85 years) in the U.S. National Health and Nutrition Examination Survey III (1988-1994), a nationally representative cohort (n = 33,994; 2 months-85 years) with vital status follow-up to 2000. Hazard ratios (HRs) for mortality associated with baseline clinically raised (≥1.00 mg/dL) and intermediate (≥0.22-0.99 mg/dL) CRP levels were estimated using Cox proportional hazards regression controlling for CRC risk factors. There were 59 deaths from CRC, 106 from other obesity-related cancers (other-ORCs) and 1,130 from cardiovascular disease (CVD). Participants with clinically raised CRP at baseline were found to have a statistically significant greater risk of CRC death (HRs = 2.36-2.47) in comparison to persons with undetected levels. HRs were lower for death from other-ORC and CVD (1.82, 95% CI 1.05-3.15; 1.53, 95% CI 1.29-1.81, respectively). Intermediate CRP level was associated with a nonsignificant 10-21% increased risk for CRC death. HR for CRC death was higher among persons with a normal BMI (2.16, 95% 0.96-4.87, p = 0.06) compared to those who were overweight (1.22, 95% CI 0.53-2.78) or obese (1.23, 95% CI, 0.37-4.08). A similar pattern was observed for waist circumference. This effect modification suggests that the impact of chronic inflammation may be independent of excess body fat. Future research is recommended to confirm emerging data that elevated serologic CRP might reflect underlying colonic inflammation., (© 2013 UICC.)

Background: Shiftwork has been implicated as a risk factor for prostate cancer. Results from prior studies have been mixed but generally support an association between circadian disruption and prostate cancer. Our aim was to investigate the relationship between shiftwork and prostate-specific antigen (PSA) test obtained as part of the National Health and Nutrition Examination Survey (NHANES) study., Methods: We combined three NHANES surveys (2005-2010) to obtain current work schedule among employed men aged 40 to 65 years with no prior history of cancer (except nonmelanoma skin cancer). Men who reported working regular night shifts or rotating shifts were considered shiftworkers. We obtained the total and percentage free PSA test results for these men and dichotomized total PSA into less than 4.0 ng/mL or 4.0 ng/mL or greater and total PSA of 4.0 ng/mL or greater combined with percentage free PSA less than or equal to 25%. Using multivariable logistic regression models, we compared PSA level among current shiftworkers and nonshiftworkers. All statistical tests were two-sided., Results: We found a statistically significant, age-adjusted association between current shiftwork and elevated PSA at the 4.0 ng/mL or greater level (odds ratio = 2.48, 95% confidence interval [CI] = 1.08 to 5.70; P = .03). The confounder-adjusted odds ratio was 2.62 (95% CI = 1.16 to 5.95; P = .02). The confounder-adjusted odds ratio for those with total PSA of 4.0 ng/mL or greater and free PSA less than or equal to 25% was 3.13 (95% CI = 1.38 to 7.09; P = .01)., Conclusions: We observed a strong positive association with shiftwork and elevated PSA level. Our data support the notion that sleep or circadian disruption is associated with elevated PSA, indicating that shiftworking men likely have an increased risk of developing prostate cancer.

The American Medical Association House of Delegates in June of 2012 adopted a policy statement on nighttime lighting and human health. This major policy statement summarizes the scientific evidence that nighttime electric light can disrupt circadian rhythms in humans and documents the rapidly advancing understanding from basic science of how disruption of circadian rhythmicity affects aspects of physiology with direct links to human health, such as cell cycle regulation, DNA damage response, and metabolism. The human evidence is also accumulating, with the strongest epidemiologic support for a link of circadian disruption from light at night to breast cancer. There are practical implications of the basic and epidemiologic science in the form of advancing lighting technologies that better accommodate human circadian rhythmicity., (Copyright © 2013 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Exposure to light at night through shiftwork has been linked to alterations in DNA methylation and increased risk of cancer development. Using an Illumina Infinium Methylation Assay, we analyzed methylation levels of 397 CpG sites in the promoter regions of 56 normally imprinted genes to investigate whether shiftwork is associated with alteration of methylation patterns. Methylation was significantly higher at 20 CpG sites and significantly lower at 30 CpG sites (P < 0.05) in 10 female long-term shiftworkers as compared to 10 female age- and folate intake-matched day workers. The strongest evidence for altered methylation patterns in shiftworkers was observed for DLX5, IGF2AS, and TP73 based on the magnitude of methylation change and consistency in the direction of change across multiple CpG sites, and consistent results were observed using quantitative DNA methylation analysis. We conclude that long-term shiftwork may alter methylation patterns at imprinted genes, which may be an important mechanism by which shiftwork has carcinogenic potential and warrants further investigation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2012 Wiley Periodicals, Inc.)

The light-at-night theory of breast cancer causation states that a portion of the high breast cancer risk in the industrialized world, and of the rising risk in the developing word, is due to the introduction and increasing use of electricity to light the night. It is difficult to test this idea in human populations, partly because almost everyone in the modern world uses electric lighting after the sun sets. Specific hypotheses that have been tested include the notions that shift workers should be at higher risk, blind women should be at lower risk, and reported sleep duration should be inversely associated with risk. Girschik et al. (Am J Epidemiol. 2013;177(4):316-327) have tested the latter in a case-control study. Although the case-control design is useful for many questions, it is probably not useful for studies of sleep duration and health.

Results from recent molecular epidemiologic studies suggest that the core circadian genes play a role in breast tumorigenesis, possibly by influencing hormone regulation or other pathways relevant to cancer. In order to further evaluate this hypothesis, we conducted a genetic and epigenetic association study of the circadian regulator TIMELESS in breast carcinogenesis. We detected significant associations between two tagging SNPs (rs2291738 and rs7302060) in the TIMELESS gene and breast cancer among 441 breast cancer cases and 479 cancer-free controls, with apparent effect modification by ER/PR status. The presence of the C allele of rs7302060 was found to be associated with reduced breast cancer risk (OR, 0.54; 95% CI, 0.54-0.99). In addition, both the G/G genotype of rs2291738 and the C/C genotype of rs7302060 were associated with reduced risk of breast cancer among ER- or PR-positive breast cancer cases (OR, 0.46; 95% CI, 0.22-0.97 and OR, 0.36; 95% CI, 0.17-0.78, respectively). We also observed a significant association between stage II, III, and IV breast cancers and TIMELESS promoter hypomethylation in peripheral blood lymphocytes (OR, 0.35; 95% CI, 0.13-0.96) in 80 breast cancer cases and 80 age-matched controls, which is corroborated by documented overexpression of TIMELESS in breast tumor tissue compared to adjacent normal tissue. Our findings support the hypothesized role of circadian genes in breast tumorigenesis, and identify a set of circadian biomarkers for breast cancer susceptibility., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Working outside normal daytime hours is increasing worldwide and is now one of the most widespread potential carcinogenic occupational exposures. There is sufficient evidence in experimental animals that light exposure during the biologic night increases tumour growth and limited epidemiologic evidence that night shift-work cause breast cancer. Existing studies had crude definitions of shift-work and did not discriminate between shift-work systems (e.g. permanent versus rotating or evening versus night)., Methods: We performed an interview based nested case-control study within a nationwide cohort of Danish nurses, including detailed information on lifetime shift-work and potential confounders. Cases of primary breast cancer (n=310) were identified from the nationwide Danish Cancer Registry. Four control nurses were selected for each case by incidence density sampling. Odds rations (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression, with adjustment for potential confounders., Findings: Overall, nurses who worked rotating shifts after midnight had a significantly increased OR (1.8; CI 1.2-2.8) for breast cancer compared to nurses with permanent day work. No association was found in a small group of nurses with evening work and no night work (OR=0.9; 0.4-1.9). The subgroup of nurses with periods of permanent night shift in addition to rotating night and day shifts experienced an OR of 2.9 (1.1-8.0). For nurses working after midnight compared to nurses never ending work before midnight, OR in the third tertile of cumulative number of shifts was 2.2 (1.5-3.2). In an analysis of different rotating shift systems, the highest OR (2.6; 1.8-3.8) was observed for long-term day-night rotating shifts., Interpretation: The results provide further evidence that night shift-work may increase the risk for breast cancer and suggest that the largest impact on risk is associated with the most disruptive shifts., Funding: Danish Cancer Society and National Programme of Environmental Health Research., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In 2007, the International Agency for Research on Cancer classified shift work involving circadian disruption as probably carcinogenic to humans (group 2A), primarily based on experimental and epidemiologic evidence for breast cancer. In order to examine options for evidence-based preventive actions, 16 researchers in basic, epidemiological and applied sciences convened at a workshop in Copenhagen 26-27 October 2011. This paper summarizes the evidence from epidemiological and experimental studies and presents possible recommendations for prevention of the effects of night work on breast cancer. Among those studies that quantified duration of shift work, there were statistically significant elevations in risk only after about 20 years working night shift. It is unclear from these studies whether or not there is a modest but real elevated risk for shorter durations. Hence, restriction of the total number of years working night shift could be one future preventive recommendation for shift workers. The diurnal secretion of melatonin by the pineal gland with peak in secretory activity during the night is a good biochemical marker of the circadian rhythm. Disruption of the diurnal melatonin secretion pattern can be diminished by restricting the number of consecutive night shifts. Reddish light and reduced light intensity during work at night could potentially help diminish the inhibitory activity of light with strong intensity on the melatonin secretion, but further mechanistic insight is needed before definite recommendations can be made. Earlier or more intensive mammography screening among female night shift worker is not recommended because the harm-benefit ratio in this age group may not be beneficial. Preventive effects of melatonin supplementation on breast cancer risk have not been clearly documented, but may be a promising avenue if a lack of side effects can be shown even after long-term ingestion. Women with previous or current breast cancer should be advised not to work night shifts because of strong experimental evidence demonstrating accelerated tumor growth by suppression of melatonin secretion. Work during the night is widespread worldwide. To provide additional evidence-based recommendations on prevention of diseases related to night shift work, large studies on the impact of various shift schedules and type of light on circadian rhythms need to be conducted in real work environments.

Incidence of cancer in children has increased in recent decades, and known risk factors can account for only a small minority of cases. Gestation and early childhood are particularly vulnerable periods in human development and an important aspect of development is in circadian rhythmicity. Emerging evidence implicates the molecular circadian mechanism in a vast array of other physiologic functions including metabolism, DNA damage response and cell-cycle regulation. Electric light exposure at night can disrupt circadian rhythms and, thereby, many other physiologic processes that are under circadian control. On this basis, it is proposed that ill-timed electric light exposure to pregnant women, to neonates, infants, and small children may increase cancer risk in those children. There are practical implications and interventions that accrue from this idea should it later be confirmed to be true.

Context: Low overnight urinary melatonin metabolite concentrations have been associated with increased risk for breast cancer among postmenopausal women. The Postmenopausal Women's Alcohol Study was a controlled feeding study to test the effects of low to moderate alcohol intake on potential risk factors for breast cancer including serum and urinary levels of hormones and other biomarkers. Previously, we observed significant increases in concentrations of serum estrone sulfate and dehydroepiandrosterone sulfate in participants after consumption of 15 or 30 g (one or two drinks) of alcohol per day., Objective: In the present analysis, we evaluated the relationship of alcohol consumption with 24-h urinary 6-sulfatoxymelatonin (6-SMT) concentration (micrograms per 24 h)., Design and Participants: Healthy postmenopausal women (n = 51) consumed a controlled diet plus each of three treatments (a nonalcoholic placebo beverage or 15 or 30 g alcohol/d) during three 8-wk periods in random order under conditions of weight maintenance., Measures: 6-SMT was measured in 24-h urine samples that were collected at entry into the study (baseline) and at the midpoint (4 wk) and end (8 wk) of each of the three diet periods., Results: Concentration of 6-SMT was not significantly modified by the alcohol treatment after adjustment for body mass index, hours of sleep, daylight hours, and baseline level of 6-SMT., Conclusions: These results suggest that low to moderate daily alcohol consumption does not significantly affect 24-h urinary levels of melatonin among healthy postmenopausal women.

Epigenetic association studies have demonstrated differential promoter methylation in the core circadian genes in breast cancer cases relative to cancer-free controls. The current pilot study aims to investigate whether epigenetic changes affecting breast cancer risk could be caused by circadian disruption through exposure to light at night. Archived DNA samples extracted from whole blood of 117 female subjects from a prospective cohort conducted in Denmark were included in this study. A polymerase chain reaction (PCR)-based method was used for detection of gene-promoter methylation, whereas genome-wide methylation analysis was performed using the Illumina Infinium Methylation Chip. Long-term shiftwork resulted in the same promoter hypomethylation of CLOCK and hypermethylation of CRY2, as was previously observed in breast cancer case-control studies. Genome-wide methylation analysis further discovered widespread methylation alterations in shiftworkers, including changes in many methylation- and cancer-relevant genes. Pathway analysis of the genes with altered methylation patterns revealed several cancer-related pathways. One of the top three networks generated was designated as "DNA replication, recombination, and repair, gene expression, behavior" with ESR1 (estrogen receptor α) featured most prominently in the network, underscoring the potential breast cancer relevance of the genes differentially methylated in long-term shiftworkers. These results, although exploratory, demonstrate the first evidence of the cancer-relevant epigenetic effects of night shiftwork, which warrant further investigation. Considering there are millions of shiftworkers worldwide, understanding the effects of this exposure may lead to novel strategies for cancer prevention and new policies regulating shiftwork.

Iron can be a potent pro-oxidant and, on this basis, elevated body iron may increase the risk of cancer. Although epidemiological evidence is mixed, there is overall support for this possibility. In addition, because of this same oxidative capacity, body iron levels may alter radiation sensitivity. In the present study, a nested case-control study of breast cancer was conducted in Japanese atomic bomb survivors. Stored serum samples from the Adult Health Study cohort were assayed for ferritin levels and joint statistical analyses were conducted of ferritin and radiation dose on the risk of breast cancer. Serum ferritin is the best feasible indicator of body iron levels in otherwise healthy people. A total of 107 cases and 212 controls were available for analysis. The relative risk (RR) of breast cancer for a 1 log unit increase in ferritin was 1.4 (95% confidence interval 1.1-1.8). This translates to an RR of 1.64 comparing high and low values of the interquartile range among controls (58 and 13.2 ng/mL, respectively). The results support the hypothesis that elevated body iron stores increase the risk of breast cancer. However, the study was inconclusive regarding the question of whether body iron alters radiation-induced breast cancer risk., (© 2011 Japanese Cancer Association.)

Levels of exposure to ionizing radiation are increasing for women worldwide due to the widespread use of CT and other radiologic diagnostic modalities. Exposure to ionizing radiation as well as increased levels of estradiol and other sex hormones are acknowledged breast cancer risk factors, but the effects of whole-body radiation on serum hormone levels in cancer-free women are unknown. This study examined whether ionizing radiation exposure is associated with levels of serum hormones and other markers that may mediate radiation-associated breast cancer risk. Serum samples were measured from cancer-free women who attended biennial health examinations with a wide range of past radiation exposure levels (N  =  412, ages 26-79). The women were selected as controls for separate case-control studies from a cohort of A-bomb survivors. Outcome measures included serum levels of total estradiol, bioavailable estradiol, testosterone, progesterone, prolactin, insulin-like growth factor-1 (IGF1), insulin-like growth factor-binding protein 3 (IGFBP-3), and ferritin. Relationships were assessed using repeated-measures regression models fitted with generalized estimating equations. Geometric mean serum levels of total estradiol and bioavailable estradiol increased with 1 Gy of radiation dose among samples collected from postmenopausal women (17%(1Gy), 95% CI: 1%-36% and 21%(1Gy), 95% CI: 4%-40%, respectively), while they decreased in samples collected from premenopausal women (-11%(1Gy), 95% CI: -20%-1% and -12%(1Gy), 95% CI: -20%- -2%, respectively). Interactions by menopausal status were significant (P  =  0.003 and P < 0.001, respectively). Testosterone levels increased with radiation dose in postmenopausal samples (30.0%(1Gy), 95% CI: 13%-49%) while they marginally decreased in premenopausal samples (-10%(1Gy), 95% CI: -19%-0%) and the interaction by menopausal status was significant (P < 0.001). Serum levels of IGF1 increased linearly with radiation dose (11%(1Gy), 95% CI: 2%-18%) and there was a significant interaction by menopausal status (P  =  0.014). Radiation-associated changes in serum levels of estradiol, bioavailable estradiol, testosterone and IGF1 were modified by menopausal status at the time of collection. No associations with radiation were observed in serum levels of progesterone, prolactin, IGFBP-3 or ferritin.

Introduction: Emerging research suggests a substantially greater prevalence of the adverse triple-negative (TN) subtype (human epidermal growth factor receptor [HER]2(-), estrogen receptor [ER](-), and progesterone receptor [PR])(-)) among black patients with breast cancer. No reports however have been generated from a statewide cancer registry., Patients and Methods: The study consisted of all black patients (N = 643) and a random sample of white patients (n = 719) diagnosed with primary invasive breast cancer (2000-2003) listed in the National Cancer Institute-Surveillance Epidemiology and End Results (NCI-SEER) Connecticut Tumor Registry (CTR). HER2 status was obtained from pathology reports submitted to the registry. Remaining data were obtained from the registry database., Results: TN tumors were more prevalent in black compared with white patients (30.8% vs. 11.2%, respectively; P < .001.) There was a 2-fold greater frequency of ER(-) and PR(-) phenotypes among black patients, but HER2 status did not differ by race. Patients with lobular cancer were less likely to have TN breast cancer compared with patients with ductal tumors (odds ratio [OR] = 0.23; 95% confidence interval [CI], 0.10-0.58). Among patients with regional disease, black patients exhibited increased risk of death (relative risk [RR] = 2.71; 95% CI, 1.48-4.97) independent of TN status. No survival disparity was found among patients with local disease., Discussion: These registry-based data corroborate reports that TN breast cancer varies substantially by race and histologic subtype. A survival disparity among patients with advanced disease, but not local disease, casts some doubt on TN status as an explanation for differences., Conclusion: More research is warranted to understand why black patients with advanced breast cancer may be at increased risk for death whether or not their tumors express the TN phenotype., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood., Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies., Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer., Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

Associations between night work and breast cancer risk were investigated in a nested case-control study within a cohort of 49,402 Norwegian nurses. A total of 699 (74%) of the live cases diagnosed in 1990-2007 and 895 (65%) controls, cancer free at the time of sampling, were interviewed about work history and potential risk factors. The odds ratios for risk of breast cancer in relation to different exposure metrics were estimated by multivariate unconditional logistic regression models. No increase of risk was found after long duration of work by nurses working ≥3 night shifts per month. Small, nonsignificantly increased risks were observed for exposure to ≥30 years in hospitals or other institutions (odds ratio (OR) = 1.1), ≥12 years in schedules including night work (OR = 1.3), ≥1,007 night shifts during the lifetime (OR = 1.2), and lifetime average number of ≥4 night shifts per month (OR = 1.2). Nonsignificantly increased risks of breast cancer were observed in nurses who worked ≥5 years with ≥4 (OR = 1.4) and ≥5 (OR = 1.6) consecutive night shifts. Significantly increased risks were seen in nurses who worked ≥5 years with ≥6 consecutive night shifts (OR = 1.8, 95% confidence interval: 1.1, 2.8). The results suggest that risk may be related to number of consecutive night shifts.

Based on the idea that electric light at night might account for a portion of the high and rising risk of breast cancer worldwide, it was predicted long ago that women working a non-day shift would be at higher risk compared with day-working women. This hypothesis has been extended more recently to prostate cancer. On the basis of limited human evidence and sufficient evidence in experimental animals, in 2007 the International Agency for Research on Cancer (IARC) classified 'shift work that involves circadian disruption' as a probable human carcinogen, group 2A. A limitation of the epidemiological studies carried out to date is in the definition of 'shift work.' IARC convened a workshop in April 2009 to consider how 'shift work' should be assessed and what domains of occupational history need to be quantified for more valid studies of shift work and cancer in the future. The working group identified several major domains of non-day shifts and shift schedules that should be captured in future studies: (1) shift system (start time of shift, number of hours per day, rotating or permanent, speed and direction of a rotating system, regular or irregular); (2) years on a particular non-day shift schedule (and cumulative exposure to the shift system over the subject's working life); and (3) shift intensity (time off between successive work days on the shift schedule). The group also recognised that for further domains to be identified, more research needs to be conducted on the impact of various shift schedules and routines on physiological and circadian rhythms of workers in real-world environments.