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

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Efforts towards the bibliographic control of Grey Literature in Ghana

Until very recently, little attention had been paid to grey literature in most developing countries including Ghana. Increasingly, FE is gaining importance all over the world and developing countries are also beginning to recognize their importance. The many varied features and sometimes unique charcteristics of grey literature have rendered them rather problematic, even though some of the features favour the not very rich countries who cannot afford to produce all the material they require from foreign sources. Efforts in Ghana to effect national bibliographic control started very well but in the last two decades or so the situation has declined rather sharply. Attempts at complementing these efforts soon started with the establishment of the Central Reference and research Library of the Council for Scientific and Industrial research (CSIR). These have gained increasing support and some advancement has been made although there remains room for improvement, especially with regard to the identification and acquisition of grey literature. In handling grey literature in developing countries, the assertion is made that there need not be any sharp distinction between conventional and non- conventional literature since their total imprints are generally small, especially with regard to conventional literature, and also because the non-conventional type or grey literature tend to contain information that cannot be obtained from anywhere else. It is therefore recommended that developing country library and information centres should have a more global perception of information sources, and adopt the strategy of networking and resource-sharing their problems.Includes: Conference preprint, Pratt student commentaryXAInternationa

The impact of atmospheric deposition of non-acidifying substances on the quality of European forest soils and the North Sea

In the pilot study ESQUAD the impact of atmospheric deposition of three heavy metals (cadmium, copper and lead) and two persistent organic pollutants (benzo(a)pyrene and lindane) on the quality of European soils and seawater has been calculated. Calculations have been made of atmospheric transport and deposition using a detailed emissions database for Europe. This enabled deposition maps to be produced to a resolution of approximately 50 km. The distribution of pollutant concentrations in forest soils was calculated for each grid cell using a database of soil property parameters in Europe. For the North Sea, a model was used to map long-term concentrations in water and sediment, which are due to atmospheric deposition and other, non-atmospheric sources. The model calculations allowed detailed comparisons of deposition fluxes and concentrations of the substances studied with critical loads and environmental quality threshold values, including critical loads. Although significant uncertainties were identified, the study gives insight in how threshold exceedance rates in Europe relate to pollutant type, threshold type, environmental compartment and chemophysical phase (adsorbed, dissolved). For all pollutants and for all compartments exceedances were calculated for at least some of the quality thresholds that were chosen