125 research outputs found
Breast Cancer Incidence After Risk-Reducing Salpingo-Oophorectomy in BRCA1 and BRCA2 Mutation Carriers
Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 mutation carriers effectively reduces ovarian cancer risk, but also reduces breast cancer risk. Breast cancer risk reductions up to 50% have been reported for both BRCA1 and BRCA2 mutation carriers, but recent prospective studies were not able to reproduce this finding for BRCA1 mutation carriers. Breast cancer incidence after RRSO was assessed in a consecutive series of 104 BRCA1 and 58 BRCA2 mutation carriers. On the basis of data from our own centre, and assuming a 50% risk reduction through RRSO at premenopausal age, we expected to find 8 breast cancers (range 6-10) in this population for the reported screening period (532 women-years). In 162 carriers with a median age of 41 years at RRSO, 13 incident breast cancers were diagnosed. In BRCA1 mutation carriers, 12 incident breast cancers were found compared with 5 (range 3-6) expected and in BRCA2 mutation carriers 1 breast cancer was found compared with 3 (range 2-5) expected. Breast cancer incidence after premenopausal RRSO is still high, especially in BRCA1 mutation carriers. Previously reported breast cancer risk reductions up to 50% were not confirmed. As a consequence, continued intensive screening for breast cancer is warranted in BRCA1 and BRCA2 mutation carriers after RRSO
Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at TeV
The elliptic, , triangular, , and quadrangular, , azimuthal
anisotropic flow coefficients are measured for unidentified charged particles,
pions and (anti-)protons in Pb-Pb collisions at TeV
with the ALICE detector at the Large Hadron Collider. Results obtained with the
event plane and four-particle cumulant methods are reported for the
pseudo-rapidity range at different collision centralities and as a
function of transverse momentum, , out to GeV/.
The observed non-zero elliptic and triangular flow depends only weakly on
transverse momentum for GeV/. The small dependence
of the difference between elliptic flow results obtained from the event plane
and four-particle cumulant methods suggests a common origin of flow
fluctuations up to GeV/. The magnitude of the (anti-)proton
elliptic and triangular flow is larger than that of pions out to at least
GeV/ indicating that the particle type dependence persists out
to high .Comment: 16 pages, 5 captioned figures, authors from page 11, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186
Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at = 2.76 TeV
The yield of charged particles associated with high- trigger
particles ( GeV/) is measured with the ALICE detector in
Pb-Pb collisions at = 2.76 TeV relative to proton-proton
collisions at the same energy. The conditional per-trigger yields are extracted
from the narrow jet-like correlation peaks in azimuthal di-hadron correlations.
In the 5% most central collisions, we observe that the yield of associated
charged particles with transverse momenta GeV/ on the
away-side drops to about 60% of that observed in pp collisions, while on the
near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/350
The BRCA2 c.68-7T > A variant is not pathogenic : A model for clinical calibration of spliceogenicity
Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44x10(-115). There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants.Peer reviewe
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
KK correlations in pp collisions at TeV from the LHC ALICE experiment
Identical neutral kaon pair correlations are measured in TeV pp
collisions in the ALICE experiment. One-dimensional KK correlation
functions in terms of the invariant momentum difference of kaon pairs are
formed in two multiplicity and two transverse momentum ranges. The femtoscopic
parameters for the radius and correlation strength of the kaon source are
extracted. The ft includes quantum statistics and final-state
interactions of the a/f resonance. KK correlations show an
increase in radius for increasing multiplicity and a slight decrease in radius
for increasing transverse mass, , as seen in correlations
in the pp system and in heavy-ion collisions. Transverse mass scaling is
observed between the KK and radii. Also, the frst
observation is made of the decay of the f(1525) meson into the
KK channel in pp collisions.Comment: 17 pages, 7 captioned figures, 2 tables, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/310
Transverse momentum spectra of charged particles in proton-proton collisions at GeV with ALICE at the LHC
The inclusive charged particle transverse momentum distribution is measured
in proton-proton collisions at GeV at the LHC using the ALICE
detector. The measurement is performed in the central pseudorapidity region
over the transverse momentum range GeV/.
The correlation between transverse momentum and particle multiplicity is also
studied. Results are presented for inelastic (INEL) and non-single-diffractive
(NSD) events. The average transverse momentum for is (stat.) (syst.) GeV/ and
\left_{\rm NSD}=0.489\pm0.001 (stat.) (syst.)
GeV/, respectively. The data exhibit a slightly larger than measurements in wider pseudorapidity intervals. The results are
compared to simulations with the Monte Carlo event generators PYTHIA and
PHOJET.Comment: 20 pages, 8 figures, 2 tables, published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/390
Inclusive J/psi production in pp collisions at sqrt(s) = 2.76 TeV
The ALICE Collaboration has measured inclusive J/psi production in pp
collisions at a center of mass energy sqrt(s)=2.76 TeV at the LHC. The results
presented in this Letter refer to the rapidity ranges |y|<0.9 and 2.5<y<4 and
have been obtained by measuring the electron and muon pair decay channels,
respectively. The integrated luminosities for the two channels are L^e_int=1.1
nb^-1 and L^mu_int=19.9 nb^-1, and the corresponding signal statistics are
N_J/psi^e+e-=59 +/- 14 and N_J/psi^mu+mu-=1364 +/- 53. We present
dsigma_J/psi/dy for the two rapidity regions under study and, for the forward-y
range, d^2sigma_J/psi/dydp_t in the transverse momentum domain 0<p_t<8 GeV/c.
The results are compared with previously published results at sqrt(s)=7 TeV and
with theoretical calculations.Comment: 7 figures, 3 tables, accepted for publication in Phys. Lett.
(Anti-)deuteron production in pp collisions at 1as=13TeV
The study of (anti-)deuteron production in pp collisions has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. In this paper the production of (anti-)deuterons is studied as a function of the charged particle multiplicity in inelastic pp collisions at s=13 TeV using the ALICE experiment. Thanks to the large number of accumulated minimum bias events, it has been possible to measure (anti-)deuteron production in pp collisions up to the same charged particle multiplicity (d Nch/ d \u3b7 3c 26) as measured in p\u2013Pb collisions at similar centre-of-mass energies. Within the uncertainties, the deuteron yield in pp collisions resembles the one in p\u2013Pb interactions, suggesting a common formation mechanism behind the production of light nuclei in hadronic interactions. In this context the measurements are compared with the expectations of coalescence and statistical hadronisation models (SHM)
Neutral pion and meson production in proton-proton collisions at TeV and TeV
The first measurements of the invariant differential cross sections of
inclusive and meson production at mid-rapidity in proton-proton
collisions at TeV and TeV are reported. The
measurement covers the ranges GeV/ and GeV/ for
these two energies, respectively. The production of mesons was measured
at TeV in the range GeV/. Next-to-Leading Order
perturbative QCD calculations, which are consistent with the spectrum
at TeV, overestimate those of and mesons at
TeV, but agree with the measured ratio at
TeV.Comment: 17 pages, 5 captioned figures, 2 tables, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/310
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