Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Small core flood experiments for foam EOR: Screening surfactant applications

Aqueous foams are a means of increasing the sweep efficiency of enhanced oil recovery processes. An understanding of how a foam behaves in the presence of oil is therefore of great importance when selecting suitable surfactants for EOR processes. The consensus is currently that the most reliable method for determining the foam behavior in the presence of oil is to inject foam through a rock core. Coreflood tests, however, are typically carried out using large rock cores (e.g. diameter = 4 cm, length = 40 cm or longer), and hence foam flow tests can take days or weeks to achieve steady-state flow. In this study, we present the preliminary results for a core-flood system where the rock core is pen-sized (diameter = 1 cm, length = 17 cm). These small cores allow for short-duration foam flow tests, where steady-state flow is achieved in a few hours. Using this system, the foam quality/effective viscosity response curves can be plotted, both with and without oil in the system. These small size cores then enable rapid screening of surfactants and foam properties in different rocks and with different oils. Benefits and limitations of these small coreflood experiments are discussed.Geoscience & EngineeringCivil Engineering and Geoscience

Surfactant Screening for Foam EOR: Correlation between Bulk and Core-Flood Experiments

tAqueous foams play an important role in many industrial processes, from ore separation by froth flotationto enhanced oil recovery (EOR). In the latter case, the foam is used as a means of increasing the sweepefficiency through the oil bearing rock – the complex, structure dependent, flow behavior of the foammeans that it has improved penetration of lower permeability regions than would be obtained with aNewtonian fluid. An understanding of how foam behaves when flowing through a rock is therefore of greatimportance when selecting suitable surfactants for EOR processes. Previous tests have suggested thatthere is no reliable correlation between bulk foam behavior and foam behavior in a rock core, especially inthe presence of oil. We present a comparative study of bulk stability tests and core floods with foam, bothwith and without oil. Core-flood tests were conducted in rock cores with a diameter of 1 cm, significantlysmaller than typical cores. Apparent viscosity/injected gas fraction response curves were obtained, bothwith and without oil in the system.The current work finds that, in the absence of oil, there is a positive correlation between bulk foamstability and core-flood performance. Bulk foam experiments can therefore be a useful screening tool togive a good indication of the surfactant performance in the core flood. However, in the presence of oil,although there was a general trend of increasing maximum apparent viscosity with increasing bulk foamstability, no strong correlation was found between bulk foam stability and the performance in the corefor the experiments performed.Petroleum Engineerin

"Finding my way in a maze while the clock is ticking": The daily life challenges of adolescents and young adults with an uncertain or poor cancer prognosis

IntroductionIncreasingly more adolescent and young adult (AYA, aged 18-39 years) patients with an uncertain and/or poor cancer prognosis (UPCP) are gaining life-years because of novel treatments or refinement of established therapies, and sometimes even face the prospect of long-term disease control. This study aims to examine the challenges of AYAs with a UPCP in daily life to inform the development of AYA care programs. MethodsSemi-structured in-depth interviews were conducted among AYAs with a UPCP. Since we expected differences in experiences between three AYA subgroups, we interviewed patients of these subgroups (1): traditional survivors (2), low-grade glioma survivors, and (3) new survivors. Interviews were analyzed using elements of grounded theory. AYA patients were actively involved as research partners. ResultsIn total 46 AYAs with UPCP participated and shared their challenges in daily life. They were on average 33.4 years old (age range 23-44) and most of them were women (63%). The most common tumor types were low-grade gliomas (16), sarcomas (7), breast cancers (6), and lung cancers (6). We identified five primary themes: (1) feeling inferior to previous self and others (e.g. feeling useless, who wants me in a relationship), (2) feeling of being alone (e.g. lonely thoughts, nobody really gets me), (3) ongoing confrontation (e.g. it is always there, own decline), (4) grief about life (e.g. grief about life I did not get, grief about old life), and (5) loss of control over the future (e.g. not able to make future plans, waiting for growth). Although all of the challenges were identified in the three AYA subgroups, the perceived intensity of the challenges differed slightly between the subgroups. DiscussionAYAs living with a UPCP experience challenges associated to their sense of altered identity, their position in the social network, and the future uncertainties. This study highlights the importance to recognize and acknowledge the unique challenges of this group. To provide age-specific care, it is important to embed acceptance and commitment therapy and AYA peer support within the healthcare system and other care programs to support AYAs to live well with their disease.Neurolog