Common germline polymorphisms associated with breast cancer-specific survival

Abstract Introduction Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. Methods A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. Results Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease. Conclusions Although no variants reached genome-wide significance (P <5 x 10−8), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels

Identification of Novel Genetic Markers of Breast Cancer Survival

Background: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. Methods: We conducted a large meta-analysis of studies in populations of European ancestry, including 37 954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200 000 and 900 000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23 059 ER-positive patients (1333 events). All statistical tests were two-sided. Results: We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10(-8)). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust. Conclusions: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors.Peer reviewe

3MeerLICHT and BlackGEM: custom-built telescopes to detect faint optical transients

We present the MeerLICHT and BlackGEM telescopes, which are wide-field optical telescopes that are currently being built to study transient phenomena, gravitational wave counterparts and variable stars. The telescopes have 65 cm primary mirrors and a 2.7 square degree field-of-view. The MeerLICHT and BlackGEM projects have different science goals, but will use identical telescopes. The first telescope, MeerLICHT, will be commissioned at Sutherland (South Africa) in the first quarter of 2017. It will co-point with MeerKAT to collect optical data commensurate with the radio observations. After careful analysis of MeerLICHT's performance, three telescopes of the same type will be commissioned in La Silla (Chile) in 2018 to form phase I of the BlackGEM array. BlackGEM aims at detecting and characterizing optical counterparts of gravitational wave events detected by Advanced LIGO and Virgo. In this contribution we present an overview of the science goals, the design and the status of the two projects

MeerKAT HI commissioning observations of MHONGOOSE galaxy ESO 302-G014

Aims. We present the results of three commissioning H I observations obtained with the MeerKAT radio telescope. These observations make up part of the preparation for the forthcoming MHONGOOSE nearby galaxy survey, which is a MeerKAT large survey project that will study the accretion of gas in galaxies and the link between gas and star formation. Methods. We used the available H I data sets, along with ancillary data at other wavelengths, to study the morphology of the MHONGOOSE sample galaxy, ESO 302-G014, which is a nearby gas-rich dwarf galaxy. Results. We find that ESO 302-G014 has a lopsided, asymmetric outer disc with a low column density. In addition, we find a tail or filament of H I clouds extending away from the galaxy, as well as an isolated H I cloud some 20 kpc to the south of the galaxy. We suggest that these features indicate a minor interaction with a low-mass galaxy. Optical imaging shows a possible dwarf galaxy near the tail, but based on the current data, we cannot confirm any association with ESO 302-G014. Nonetheless, an interaction scenario with some kind of low-mass companion is still supported by the presence of a significant amount of molecular gas, which is almost equal to the stellar mass, and a number of prominent stellar clusters, which suggest recently triggered star formation. Conclusions. These data show that MeerKAT produces exquisite imaging data. The forthcoming full-depth survey observations of ESO 302-G014 and other sample galaxies will, therefore, offer insights into the fate of neutral gas as it moves from the intergalactic medium onto galaxies

Body mass index and breast cancer survival:a Mendelian randomization analysis

Abstract Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01–1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89–1.13, P = 0.95). Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases