Obesity and Awareness of Obesity as Risk Factors for Breast Cancer in Six Ethnic Groups

Objective: To document BMI and knowledge regarding obesity as a risk factor for breast cancer among subpopulations of African‐, Caribbean‐, and European‐American women and to consider the variables predicting obesity in these diverse groups. Research Methods and Procedures: A stratified cluster‐sampling plan was used to recruit 1364 older women from Brooklyn, NY, during 2000–2002. Two groups were born in the United States (African Americans and European Americans), whereas others were from the English‐speaking Caribbean, Haiti, the Dominican Republic, and Eastern Europe. Participants provided demographics, height and weight measures, and estimates of the risk obesity posed for breast cancer. Results: Women from all groups were significantly overweight (BMI > 25 kg/m²), although European Americans were lowest, followed by Dominicans and Haitians; African‐American and English‐speaking Caribbean women fell into the obese range, even when background variables were controlled. Knowledge of obesity as a breast cancer risk factor was also poor across groups, but Dominicans and Haitians had the lowest scores on knowledge. Importantly, knowledge was not associated with BMI in the overall sample, even when controlling for demographics and ethnicity, although logistic regressions comparing normal weight women with overweight and obese groupings suggested some knowledge of breast cancer risk in the overweight, but not the obese, group. Discussion: The findings remind health professionals of the need to consider more specific ethnic groupings than has hitherto been the case, as well as consider how ethnic and cultural variables may influence perceptions of obesity and its relation to cancer risk.     

Bushmeat Consumption and Preferences of Two Ethnic Groups in Bioko Island, West Africa

We studied consumption and preference of meats of wild species (bushmeat) by inhabitants of Bioko Island, Equatorial Guinea. The aim of the study was to quantify frequency of consumption and stated preferences of the two main ethnic groups (Bubi and Fang) in the island. Although members of both ethnic groups lived on the island, the Fang originated from the continent and maintained strong links with this area. Thus, preference and consumption of the Fang reflected exposure to animals found in the continent as well as on Bioko. A sample of 196 subjects (115 Bubi and 81 Fang) was interviewed using semistructured questionnaires. A total of 55 different bushmeat species was identified as preferred or consumed by interviewees. Principal component analyses of stated consumption and preference indicated differences between ethnic groups in their general responses. Further analyses of the effects of preference and other factors on consumption of the three main species mentioned (blue duiker (Cephalophus monticola), Emin's rat (Cricetomys emini), and brush-tailed porcupine (Atherurus africanus) were undertaken. Proportional odds logistic regression models for ordered categorical response data were employed. Results indicated that age and sex of the respondent did not affect consumption, but ethnic group was statistically significant for the three-study species. Consumption and preference of the different meats (N = 11 species) in relation to their availability in the market and price was studied using multiple linear regressions. Consumption is driven predominantly by availability but there is some influence of preference; price of the meat did not have a significant influence.     

Analysis of Cancer Mutation Signatures in Blood by a Novel Ultra-Sensitive Assay: Monitoring of Therapy or Recurrence in Non-Metastatic Breast Cancer

Background

Tumor DNA has been shown to be present both in circulating tumor cells in blood and as fragments in the plasma of metastatic cancer patients. The identification of ultra-rare tumor-specific mutations in blood would be the ultimate marker to measure efficacy of cancer therapy and/ or early recurrence. Herein we present a method for detecting microinsertions/deletions/indels (MIDIs) at ultra-high analytical selectivity. MIDIs comprise about 15% of mutations.

Methods and Findings

We describe MIDI-Activated Pyrophosphorolysis (MAP), a method of ultra-high analytical selectivity for detecting MIDIs. The high analytical selectivity of MAP is putatively due to serial coupling of two rare events: heteroduplex slippage and mis-pyrophosphorolysis. MAP generally has an analytical selectivity of one mutant molecule per >1 billion wild type molecules and an analytical sensitivity of one mutant molecule per reaction. The analytical selectivity of MAP is about 100,000-fold better than that of our previously described method of Pyrophosphorolysis Activated Polymerization-Allele specific amplification (PAP-A) for detecting MIDIs. The utility of this method is illustrated in two ways. 1) We demonstrate that two EGFR deletions commonly found in lung cancers are not present in tissue from four normal human lungs (10⁷ copies of gDNA each) or in blood samples from 10 healthy individuals (10⁷ copies of gDNA each). This is inconsistent, at least at an analytical sensitivity of 10⁻⁷, with the hypotheses of (a) hypermutation or (b) strong selection of these growth factor-mutated cells during normal lung development leads to accumulation of pre-neoplastic cells with these EGFR mutations, which sometimes can lead to lung cancer in late adulthood. Moreover, MAP was used for large scale, high throughput “gene pool” analysis. No germline or early embryonic somatic mosaic mutation was detected (at a frequency of >0.3%) for the 15/18 bp EGFR deletion mutations in 6,400 individuals, suggesting that early embryonic EGFR somatic mutation is very rare, inconsistent with hypermutation or strong selection of these deletions in the embryo. 2) The second illustration of MAP utility is in personalized monitoring of therapy and early recurrence in cancer. Tumor-specific p53 mutations identified at diagnosis in the plasma of six patients with stage II and III breast cancer were undetectable after therapy in four women, consistent with clinical remission, and continued to be detected after treatment in two others, reflecting tumor progression.

Conclusions

MAP has an analytical selectivity of one part per billion for detection of MIDIs and an analytical sensitivity of one molecule. MAP provides a general tool for monitoring ultra-rare mutations in tissues and blood. As an example, we show that the personalized cancer signature in six out of six patients with non-metastatic breast cancer can be detected and that levels over time are correlated with the clinical course of disease.     

The Association of Neighborhood Social Capital and Ethnic (Minority) Density with Pregnancy Outcomes in the Netherlands

Background

Perinatal morbidity rates are relatively high in the Netherlands, and significant inequalities in perinatal morbidity and mortality can be found across neighborhoods. In socioeconomically deprived areas, ‘Western’ women are particularly at risk for adverse birth outcomes. Almost all studies to date have explained the disparities in terms of individual determinants of birth outcomes. This study examines the influence of neighborhood contextual characteristics on birth weight (adjusted for gestational age) and preterm birth. We focused on the influence of neighborhood social capital – measured as informal socializing and social connections between neighbors – as well as ethnic (minority) density.

Methods

Data on birth weight and prematurity were obtained from the Perinatal Registration Netherlands 2000–2008 dataset, containing 97% of all pregnancies. Neighborhood-level measurements were obtained from three different sources, comprising both survey and registration data. We included 3.422 neighborhoods and 1.527.565 pregnancies for the birth weight analysis and 1.549.285 pregnancies for the premature birth analysis. Linear and logistic multilevel regression was performed to assess the associations of individual and neighborhood level variables with birth weight and preterm birth.

Results

We found modest but significant neighborhood effects on birth weight and preterm births. The effect of ethnic (minority) density was stronger than that of neighborhood social capital. Moreover, ethnic (minority) density was associated with higher birth weight for infants of non-Western ethnic minority women compared to Western women (15 grams; 95% CI: 12,4/17,5) as well as reduced risk for prematurity (OR 0.97; CI 0,95/0,99).

Conclusions

Our results indicate that neighborhood contexts are associated with birth weight and preterm birth in the Netherlands. Moreover, ethnic (minority) density seems to be a protective factor for non-Western ethnic minority women, but not for Western women. This helps explain the increased risk of Western women in deprived neighborhoods for adverse birth outcomes found in previous studies.     

Fish assemblages associated with urban structures and natural reefs in Sydney,Australia

Abstract Fish ecology in urban estuaries is poorly understood. As coastal landscapes are transformed, recognizing the impact that urban structures, such as marinas, seawalls and wharfs, have on local fish populations is becoming increasingly important. The extent to which fish are able to maintain natural ecological assemblages can be measured, to a certain extent, by how closely they mimic natural habitats. In Sydney Harbour, assemblages of fish associated with artificial structures were compared with those associated with natural rocky reefs. Sampling was carried out in five locations, each with a marina, swimming enclosure and natural reef. In each location, different habitats supported different assemblages, but differences between habitats were not consistent among locations. Subsequent sampling compared artificial and natural sites in three different areas in each of three different estuaries. Results indicated that differences in fish assemblages between artificial and natural sites were greater than differences between sites within each habitat, but there were no patterns among different positions in an estuary or from estuary to estuary. This study provides initial evidence that, although artificial habitats generally support the same species as found on natural reefs, assemblages usually differed between natural and artificial habitats. In addition, without knowing if these habitats do, in fact, sustain viable populations of fish, it would be premature to label artificial structures as effective habitat for fish.     

Exercise Performance: Its Relationship with Morphological and Functional Characteristics in Two Ethnic Groups of Yakutia

Morphological and functional criteria permitting the prediction of exercise performance were identified for two ethnic groups of Yakutia (Sakha). Yakuts with a low body height, normotonic autonomic nervous regulation, a relatively high weight-height index, eukinetic blood circulation, and a high specific exercise performance are best adapted to the environment. A high exercise performance in sympathicotonic subgroups cannot be a criterion of good adaptation because it is accompanied by cardiovascular strain even at rest. A high prevalence of sympathicotonia and body weight deficit in the ethnic groups studied reflect maladaptations caused by a set of adverse natural and social environmental factors.__________Translated from Fiziologiya Cheloveka, Vol. 31, No. 3, 2005, pp. 124–130.Original Russian Text Copyright © 2005 by Stepanova.     

Feasibility and Accuracy of Sentinel Lymph Node Biopsy in Clinically Node-Positive Breast Cancer after Neoadjuvant Chemotherapy: A Meta-Analysis

Sentinel lymph node biopsy (SLNB) has replaced conventional axillary lymph node dissection (ALND) in axillary node-negative breast cancer patients. However, the use of SLNB remains controversial in patients after neoadjuvant chemotherapy (NAC). The aim of this review is to evaluate the feasibility and accuracy of SLNB after NAC in clinically node-positive patients. Systematic searches were performed in the PubMed, Embase, and Cochrane Library databases from 1993 to December 2013 for studies on node-positive breast cancer patients who underwent SLNB after NAC followed by ALND. Of 436 identified studies, 15 were included in this review, with a total of 2,471 patients. The pooled identification rate (IR) of SLNB was 89% [95% confidence interval (CI) 85–93%], and the false negative rate (FNR) of SLNB was 14% (95% CI 10–17%). The heterogeneity of FNR was analyzed by meta-regression, and the results revealed that immunohistochemistry (IHC) staining may represent an independent factor (P = 0.04). FNR was lower in the IHC combined with hematoxylin and eosin (H&E) staining subgroup than in the H&E staining alone subgroup, with values of 8.7% versus 16.0%, respectively (P = 0.001). Thus, SLNB was feasible after NAC in node-positive breast cancer patients. In addition, the IR of SLNB was respectable, although the FNR of SLNB was poor and requires further improvement. These findings indicate that IHC may improve the accuracy of SLNB.     

两种人乳腺癌裸鼠移植模型的建立

目的建立简便的人乳腺癌裸鼠移植模型,并探讨其部分生物学特性。方法采用雌激素受体阴性的MDA-MB-231和SK-BR-3人乳腺癌细胞株,分别接种于10只裸鼠左侧腋窝皮下,移植细胞总数为1×107/只。观察肿块生长情况,第42天处死荷瘤鼠,切除肿块作病理切片。结果 MDA-MB-231接种后第5d在接种部位可见结节,成瘤率为90%（9/10）,接种42 d肿瘤体积426.6±333.8,瘤重0.417±0.276,病理学检查为浸润性导管癌;SK-BR-3接种后第11天在接种部位可见结节,成瘤率为80%（8/10）,接种42 d肿瘤体积357.5±246,瘤重0.325±0.167,病理学检查为浸润性导管癌。结论该方法建立的人乳腺癌裸鼠移植模型,皮下移植方法简单,易于操作,成功率较高,肿瘤可部分保持人乳腺癌生物学特性,为研究人乳腺癌提供了重要工具。     

Two new Senotheca (Glossopteridales) species from the Sydney Basin,Australia, and a review of the genus

The fertile glossopterid Senotheca is represented by linear fructifications with broad wings attached to the midribs of Glossopteris leaves. The architecture of the reproductive structures supports their placement within the Dictyopteridiaceae. The genus is emended, the validity of two established species (Senotheca murulidihensis and S. kingii) is confirmed, two new species (Senotheca keiraensis and S. magna) are formally defined and one taxon characterized by an attached leaf with coarse venation is retained under open nomenclature. Senotheca is distributed from northeastern India to eastern Australia and ranges from the (?)Artinskian to Changhsingian but the biostratigraphic utility of the genus is constrained by its rarity. Several other reports of the genus from Antarctica and southeastern Australia remain doubtful.     

The Association of 25 Hydroxyvitamin D and Parathyroid Hormone with Metabolic Syndrome in Two Ethnic Groups in South Africa

Introduction

Though inconsistent, a number of studies have shown an association between vitamin D (25(OH)D) status, parathyroid hormone (PTH) and the metabolic syndrome (Met S). These have largely been carried out in Caucasians or black subjects living in high income countries. There no data on the relationship of 25(OH)D and PTH status with Met S in populations resident in Africa. The aims of this study were to evaluate if there was an association of 25(OH)D or PTH with Met S in non-Caucasian populations in South Africa, and whether these molecules explained ethnic differences in the prevalence of Met S and its individual components.

Methods

We measured anthropometry, serum 25(OH)D and PTH levels and the components of Met S, plus related metabolic variables, in 374 African and 350 Asian Indian healthy adults from the greater Johannesburg metropolitan area.

Results

Met S was diagnosed in 29% of the African and 46% of the Asian Indian subjects (p<0.0001). Subjects with Met S had higher PTH than those without Met S, (p<0.0001), whilst 25(OH)D levels were not significantly different (p = 0.50). In multivariate analysis, 25(OH)D was not associated with any components of the Met S however PTH was shown to be positively associated with systolic (p = 0.018) and diastolic (p = 0.005) blood pressures and waist circumference (p<0.0001) and negatively associated with HOMA (p = 0.0008) levels. Logistic regression analysis showed that Asian Indian ethnicity (OR 2.24; 95% CIs 1.57, 3.18; p<0.0001) and raised PTH (OR 2.48; 95% CIs 1.01, 6.08; p = 0.04; adjusted for 25(OH)D) produced an increased risk of Met S but 25(OH)D did not (OR 1.25; 95% CI 0.67, 2.24; p = 0.48).

Conclusions

Plasma PTH but not 25(OH)D is an independent predictor of the Met S in African and Asian Indians in South Africa.     

DNA Methylation Patterns Can Estimate Nonequivalent Outcomes of Breast Cancer with the Same Receptor Subtypes

Breast cancer has various molecular subtypes and displays high heterogeneity. Aberrant DNA methylation is involved in tumor origin, development and progression. Moreover, distinct DNA methylation patterns are associated with specific breast cancer subtypes. We explored DNA methylation patterns in association with gene expression to assess their impact on the prognosis of breast cancer based on Infinium 450K arrays (training set) from The Cancer Genome Atlas (TCGA). The DNA methylation patterns of 12 featured genes that had a high correlation with gene expression were identified through univariate and multivariable Cox proportional hazards models and used to define the methylation risk score (MRS). An improved ability to distinguish the power of the DNA methylation pattern from the 12 featured genes (p = 0.00103) was observed compared with the average methylation levels (p = 0.956) or gene expression (p = 0.909). Furthermore, MRS provided a good prognostic value for breast cancers even when the patients had the same receptor status. We found that ER-, PR- or Her2- samples with high-MRS had the worst 5-year survival rate and overall survival time. An independent test set including 28 patients with death as an outcome was used to test the validity of the MRS of the 12 featured genes; this analysis obtained a prognostic value equivalent to the training set. The predict power was validated through two independent datasets from the GEO database. The DNA methylation pattern is a powerful predictor of breast cancer survival, and can predict outcomes of the same breast cancer molecular subtypes.     

Better Long-Term Survival in Young Patients with Non-Metastatic Colorectal Cancer after Surgery,an Analysis of 69,835 Patients in SEER Database

Objective

To compare the long-term survival of colorectal cancer (CRC) in young patients with elderly ones.

Methods

Using Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 69,835 patients with non-metastatic colorectal cancer diagnosed between January 1, 1988 and December 31, 2003 treated with surgery. Patients were divided into young (40 years and under) and elderly groups (over 40 years of age). Five-year cancer specific survival data were obtained. Kaplan-Meier methods were adopted and multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors.

Results

Young patients showed significantly higher pathological grading (p<0.001), more cases of mucinous and signet-ring histological type (p<0.001), later AJCC stage (p<0.001), more lymph nodes (≥12 nodes) dissected (p<0.001) and higher metastatic lymph node ratio (p<0.001). The 5-year colorectal cancer specific survival rates were 78.6% in young group and 75.3% in elderly group, which had significant difference in both univariate and multivariate analysis (P<0.001). Further analysis showed this significant difference only existed in stage II and III patients.

Conclusions

Compared with elderly patients, young patients with colorectal cancer treated with surgery appear to have unique characteristics and a higher cancer specific survival rate although they presented with higher proportions of unfavorable biological behavior as well as advanced stage disease.     

Assessment of possible sediment toxicity of contaminated sediments in Port Jackson, Sydney, Australia

A considerable amount of chemical data is available for surficial sediments in Port Jackson. Some of the highest concentrations of heavy metals, organochlorines and polycyclic aromatic hydrocarbons of any capital port occur in sediments mantling shallow tributaries and embayments close to central Sydney. However, these data have limited ability to predict adverse effects on living resources and in the absence of toxicological data, sediment quality guidelines (SQG) have been used to assess the possible adverse biological effects of sedimentary contaminants in this estuary. Several SQGs are currently available for both fresh and marine environments, but the scheme used in the current study is based on empirical analysis of matching chemical and biological data compiled by the National Oceanographic and Atmospheric Administration (NOAA) in the U.S. The NOAA SQG can be used to assess individual chemicals, or to estimate the probability of acute sediment toxicity by calculating `mean quotients' for a large range of contaminants. Although many individual chemicals in sediment exceed SQG over extensive parts of Port Jackson, `mean quotient' results suggest that only a small proportion (1%) of the harbour may be highly toxic (74% probability of toxicity). However, sediment in a considerably larger proportion of the port (almost 25%) is estimated to have a 49% probability of being toxic using the `mean quotient' approach. These results are indicative at best and contemporaneous chemical/biological/ecotoxicological studies are needed to verify the applicability of SQG developed in the U.S. for use outside North America and site specific studies of this type are still required to determine the toxicity of sediments in Port Jackson.     

The Impacts of Inclusion in Clinical Trials on Outcomes among Patients with Metastatic Breast Cancer (MBC)

Background

Metastatic breast cancer (MBC) remains a devastating and incurable disease. Over the past decade, the implementation of clinical trials both with and without molecular targeted therapeutics has impacted the daily clinical treatment of patients with MBC. In this study, we determine whether including MBC patients in clinical trials affects clinical outcomes.

Methods

We retrospectively reviewed data for a total of 863 patients diagnosed with initial or recurrent (after receiving adjuvant systemic treatments following surgery) metastatic disease between January 2000 and December 2013. Data were obtained from the breast cancer database of Samsung Medical Center.

Results

Among the 806 patients selected for inclusion, 188 (23%) had participated in clinical trials. A total of 185 clinical trials were conducted from 2000 to 2014. When compared with earlier periods (n = 10 for 2000–2004), clinical trial enrollment significantly increased over time (n = 103 for 2005–2009, P = 0.024; n = 110 for 2010–2014, P = 0.046). Multivariate analyses revealed that biologic subtype, distant recurrence free interval (DRFI), and clinical trial enrollment were independent predictors of overall survival. Patients who participated in clinical trials showed improved survival, with a hazard ratio of 0.75 (95% CI, 0.59–0.95), which was associated with a 25% reduction in the risk of death. However, subgroup analysis showed that this improved survival benefit was not maintained in patients with triple negative breast cancer (TNBC).

Conclusions

Although not conclusive, we could speculate that there were differences in the use of newer agents or regimens over time, and these differences appear to be associated with improved survival.