Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Centrality, rapidity and transverse momentum dependence of J/\u3c8 suppression in Pb-Pb collisions at 1asNN= 2.76TeV

The inclusive J/.nuclear modification factor (R-AA) in Pb-Pb collisions at root(NN)-N-S = 2.76TeVhas been measured by ALICE as a function of centrality in the e+ e-decay channel at mid-rapidity (| y| < 0.8) and as a function of centrality, transverse momentum and rapidity in the + -decay channel at forward-rapidity (2.5 < y < 4). The J/.yields measured in Pb-Pb are suppressed compared to those in ppcollisions scaled by the number of binary collisions. The RAAintegrated over a centrality range corresponding to 90% of the inelastic Pb-Pb cross section is 0.72 - 0.06(stat.) - 0.10(syst.) at mid-rapidity and 0.58 - 0.01(stat.) - 0.09(syst.) at forward-rapidity. At low transverse momentum, significantly larger values of RAAare measured at forward-rapidity compared to measurements at lower energy. These features suggest that a contribution to the J/.yield originates from charm quark (re) combination in the deconfined partonic medium

Measurement of jet quenching with semi-inclusive hadron-jet distributions in central Pb-Pb collisions at √sNN = 2.76 TeV

We report the measurement of a new observable of jet quenching in central Pb-Pb collisions at â\u88\u9asNN = 2.76 TeV, based on the semi-inclusive rate of charged jets recoiling from a high transverse momentum (high-pT) charged hadron trigger. Jets are measured using collinear-safe jet reconstruction with infrared cutoff for jet constituents of 0.15 GeV, for jet resolution parameters R = 0.2, 0.4 and 0.5. Underlying event background is corrected at the event-ensemble level, without imposing bias on the jet population. Recoil jet spectra are reported in the range 20 T,jetch < 100 GeV. Reference distributions for pp collisions at â\u88\u9as = 2.76TeV are calculated using Monte Carlo and NLO pQCD methods, which are validated by comparing with measurements in pp collisions at â\u88\u9as = 7TeV. The recoil jet yield in central Pb-Pb collisions is found to be suppressed relative to that in pp collisions. No significant medium-induced broadening of the intra-jet energy profile is observed within 0.5 radians relative to the recoil jet axis. The angular distribution of the recoil jet yield relative to the trigger axis is found to be similar in central Pb-Pb and pp collisions, with no significant medium-induced acoplanarity observed. Large-angle jet deflection, which may provide a direct probe of the nature of the quasi-particles in hot QCD matter, is explored

Production of charged pions, kaons and protons at large transverse momenta in pp and Pb–Pb collisions at sNN=2.76\sqrt{s_{NN}}=2.76 TeV

Transverse momentum spectra of pi(+/-), K-+/- and p((p) over bar) up to p(T) = 20 GeV/c at mid-rapidity in pp, peripheral (60-80%) and central (0-5%) Pb-Pb collisions at v root s(NN) = 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pionratios both show a distinct peak at p(T) approximate to 3 GeV/c in central Pb-Pb collisions. Below the peak, p(T) 10 GeV/c particle ratios in pp and Pb-Pb collisions are in agreement and the nuclear modification factors for pi(+/-), K-+/- and p((p) over bar) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets