Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression.

Breast cancer risk assessment using genetic variants and risk factors in a Singapore Chinese population.

Introduction: Genetic variants for breast cancer risk identified in genome-wide association studies (GWAS) in Western populations require further testing in Asian populations. A risk assessment model incorporating both validated genetic variants and established risk factors may improve its performance in risk prediction of Asian women.

Methods: A nested case-control study of female breast cancer (411 cases and 1,212 controls) within the Singapore Chinese Health Study was conducted to investigate the effects of 51 genetic variants identified in previous GWAS on breast cancer risk.

Pregnancy during breast cancer: does a mother's parity status modify an offspring's mortality risk?

To assess whether children born to primiparous women around the time of a breast cancer diagnosis have an increased mortality risk. From the merged Swedish Multi-Generation and Cancer Registers, we identified 49,750 eligible children whose mother was diagnosed with breast cancer between 1958 and 2010. Mortality rates in offspring were compared to the background population using standardized mortality ratios (SMR), adjusted for calendar year of birth, attained age, and sex, and calculated for each category of timing of delivery (before, around, or after mother's diagnosis) and mother's parity status.

Multivalent antiviral XTEN-peptide conjugates with long in vivo half-life and enhanced solubility.

XTENs are unstructured, nonrepetitive protein polymers designed to prolong the in vivo half-life of pharmaceuticals by introducing a bulking effect similar to that of poly(ethylene glycol). While XTEN can be expressed as a recombinant fusion protein with bioactive proteins and peptides, therapeutic molecules of interest can also be chemically conjugated to XTEN. Such an approach permits precise control over the positioning, spacing, and valency of bioactive moieties along the length of XTEN.

Metabolic disease risk in children by salivary biomarker analysis.

Objective: The study of obesity-related metabolic syndrome or Type 2 diabetes (T2D) in children is particularly difficult because of fear of needles. We tested a non-invasive approach to study inflammatory parameters in an at-risk population of children to provide proof-of-principle for future investigations of vulnerable subjects.

Design And Methods: We evaluated metabolic differences in 744, 11-year old children selected from underweight, normal healthy weight, overweight and obese categories by analyzing fasting saliva samples for 20 biomarkers.

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study.

Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.

Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium.

DNA materials: bridging nanotechnology and biotechnology.

CONSPECTUS: In recent decades, DNA has taken on an assortment of diverse roles, not only as the central genetic molecule in biological systems but also as a generic material for nanoscale engineering. DNA possesses many exceptional properties, including its biological function, biocompatibility, molecular recognition ability, and nanoscale controllability. Taking advantage of these unique attributes, a variety of DNA materials have been created with properties derived both from the biological functions and from the structural characteristics of DNA molecules.

Grounding evidence-based approaches to cancer prevention in the community: a case study of mammography barriers in underserved African American women.

When community health planners select an evidence-based intervention that has been developed and tested in one situation and adapt it for use in a different situation or community, best practice suggests needs assessment and formative research in the new setting. Cancer prevention planners who are interested in adopting and adapting evidence-based approaches need to base their choices on a sound understanding of the health or behavioral risk problem in which they mean to intervene. This requires a balancing act of weighing community information against a broader perspective from the scientific literature and using the combination to identify and adapt an evidence-based intervention program that is likely to be effective in the new setting.

Mammographic density phenotypes and risk of breast cancer: a meta-analysis.

Background: Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk.

Methods: We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk.

The heritability of prostate cancer in the Nordic Twin Study of Cancer.

Background: Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age.

Methods: To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic (MZ) and 30,054 dizygotic (DZ) same-sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability.

US health spending trends by age and gender: selected years 2002-10.

This article presents estimates of personal health care spending by age and gender in selected years during the period 2002-10 and an analysis of the variation in spending among children, working-age adults, and the elderly. Our research found that in this period, aggregate spending on children's health care increased at the slowest rate. However, per capita spending for children grew more rapidly than that for working-age adults and the elderly.

Is channel segmentation necessary to reach a multiethnic population with weight-related health promotion? An analysis of use and perception of communication channels.

Objective: To explore similarities and differences in the use and perception of communication channels to access weight-related health promotion among women in three ethnic minority groups. The ultimate aim was to determine whether similar channels might reach ethnic minority women in general or whether segmentation to ethnic groups would be required.

Design: Eight ethnically homogeneous focus groups were conducted among 48 women of Ghanaian, Antillean/Aruban, or Afro-Surinamese background living in Amsterdam.

Glucitol dehydrogenase from peach (Prunus persica) fruits is regulated by thioredoxin h.

Glucitol (Gol) is a major photosynthetic product in plants from the Rosaceae family. Herein we report the molecular cloning, heterologous expression and characterization of Gol dehydrogenase (GolDHase, EC 1.1.

Constraints on cosmic strings from the LIGO-Virgo gravitational-wave detectors.

Cosmic strings can give rise to a large variety of interesting astrophysical phenomena. Among them, powerful bursts of gravitational waves (GWs) produced by cusps are a promising observational signature. In this Letter we present a search for GWs from cosmic string cusps in data collected by the LIGO and Virgo gravitational wave detectors between 2005 and 2010, with over 625 days of live time.

Spectrum of very early breast cancer in a setting without organised screening.

Background: Within a setting without organised breast cancer screening, the characteristics and survival of very early breast cancer were determined.

Methods: All 4930 women diagnosed with breast cancer in University Malaya Medical Center, Malaysia from 1993 to 2011 were included. Factors associated with very early presentation (stage I) at diagnosis were identified.

Gene expression profiling identifies microphthalmia-associated transcription factor (MITF) and Dickkopf-1 (DKK1) as regulators of microenvironment-driven alterations in melanoma phenotype.

Background: The diversity of functional phenotypes observed within a tumor does not exclusively result from intratumoral genetic heterogeneity but also from the response of cancer cells to the microenvironment. We have previously demonstrated that the morphological and functional phenotypes of melanoma can be dynamically altered upon external stimuli.

Findings: In the present study, transcriptome profiles were generated to explore the molecules governing phenotypes of melanospheres grown in the bFGF(+)EGF(+) serum-free cultures and monolayers maintained in the serum-containing medium.

Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

Background: In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia.

Myocardial deletion of transcription factor CHF1/Hey2 results in altered myocyte action potential and mild conduction system expansion but does not alter conduction system function or promote spontaneous arrhythmias.

CHF1/Hey2 is a Notch-responsive basic helix-loop-helix transcription factor involved in cardiac development. Common variants in Hey2 are associated with Brugada syndrome. We hypothesized that absence of CHF1/Hey2 would result in abnormal cellular electrical activity, altered cardiac conduction system (CCS) development, and increased arrhythmogenesis.

An optimized and simplified system of mouse embryonic stem cell cardiac differentiation for the assessment of differentiation modifiers.

Generating cardiomyocytes from embryonic stem cells is an important technique for understanding cardiovascular development, the origins of cardiovascular diseases and also for providing potential reagents for cardiac repair. Numerous methods have been published but often are technically challenging, complex, and are not easily adapted to assessment of specific gene contributions to cardiac myocyte differentiation. Here we report the development of an optimized protocol to induce the differentiation of mouse embryonic stem cells to cardiac myocytes that is simplified and easily adapted for genetic studies.

Demographic and spatial predictors of anemia in women of reproductive age in Timor-Leste: implications for health program prioritization.

Anemia is a significant risk factor for poor health outcomes for both the mother and neonate; however, the determinants of anemia in many epidemiological settings are poorly understood. Using a subset of a nationally representative cluster survey (2010 Demographic and Health Survey) in combination with other non-contemporaneous survey data, the epidemiology of anemia among women of reproductive age in Timor-Leste has been explored. Logistic regression was used to identify risk factors, population-level impacts were estimated as population attributable fractions and spatial analytics were used to identify regions of highest risk.

Differences in late cardiovascular mortality following acute myocardial infarction in three major Asian ethnic groups.

Aim: the purpose of this study was to investigate differences in long-term mortality following acute myocardial infarction (AMI) in patients from three major ethnicities of Asia.

Methods And Results: We studied 15,151 patients hospitalized for AMI with a median follow-up of 7.3 years (maximum 12 years) in six publicly-funded hospitals in Singapore from 2000-2005.

Natural compounds' activity against cancer stem-like or fast-cycling melanoma cells.

Background: Accumulating evidence supports the concept that melanoma is highly heterogeneous and sustained by a small subpopulation of melanoma stem-like cells. Those cells are considered as responsible for tumor resistance to therapies. Moreover, melanoma cells are characterized by their high phenotypic plasticity.

Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history.

Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer. In order to improve access to testing, we developed a rapid test for recurrent mutations in our Asian populations. In this study, we designed a genotyping assay with 55 BRCA1 and 44 BRCA2 mutations previously identified in Asian studies, and validated this assay in 267 individuals who had previously been tested by full sequencing.

Relation of mitochondrial oxygen consumption in peripheral blood mononuclear cells to vascular function in type 2 diabetes mellitus.

Recent studies have shown mitochondrial dysfunction and increased production of reactive oxygen species in peripheral blood mononuclear cells (PBMCs) and endothelial cells from patients with diabetes mellitus. Mitochondria oxygen consumption is coupled to adenosine triphosphate (ATP) production and also occurs in an uncoupled fashion during formation of reactive oxygen species by components of the electron transport chain and other enzymatic sites. We therefore hypothesized that diabetes would be associated with higher total and uncoupled oxygen consumption in PBMCs that would correlate with endothelial dysfunction.

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

Background: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk.