An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Measurement of the W±Z boson pair-production cross section in pp collisions at √s=13TeV with the ATLAS detector

published_or_final_versio

Measurement of the <i>t(t)over-bar</i> production cross section in the τ plus jets final state in <i>pp</i> collisions at <i>√s</i>=8 TeV using the ATLAS detector

A measurement of the inclusive $pp\to t\bar{t}+X$ production cross section in the $\tau+{\rm jets}$ final state using only the hadronic decays of the $\tau$ lepton is presented. The measurement is performed using 20.2 fb$^{-1}$ of proton-proton collision data recorded at a center-of-mass energy of $\sqrt{s}=8$ TeV with the ATLAS detector at the Large Hadron Collider. The cross section is measured via a counting experiment by imposing a set of selection criteria on the identification and kinematic variables of the reconstructed particles and jets, and on event kinematic variables and characteristics. The production cross section is measured to be $\sigma_{t\bar{t}}= 239 \pm 29$ pb, which is in agreement with the measurements in other final states and the theoretical predictions at this center-of-mass energy

Erratum to: Measurement of the W boson polarisation in tt^{¯} events from pp collisions at √s = 8 TeV in the lepton + jets channel with Atlas

1 Erratum to: Eur. Phys. J. C (2017) 77:264 [https://doi.org/10.1140/epjc/s10052-017-4819-4]. The original article can be found online at [https://doi.org/10.1140/epjc/s10052-017-4819-4]

Measurement of the W boson polarisation in [Formula: see text] events from pp collisions at [Formula: see text] = 8 TeV in the lepton + jets channel with ATLAS.

This paper presents a measurement of the polarisation of W bosons from [Formula: see text] decays, reconstructed in events with one high-[Formula: see text] lepton and at least four jets. Data from pp collisions at the LHC were collected at [Formula: see text] = 8 TeV and correspond to an integrated luminosity of 20.2 fb[Formula: see text]. The angle [Formula: see text] between the b-quark from the top quark decay and a direct W boson decay product in the W boson rest frame is sensitive to the W boson polarisation. Two different W decay products are used as polarisation analysers: the charged lepton and the down-type quark for the leptonically and hadronically decaying W boson, respectively. The most precise measurement of the W boson polarisation via the distribution of [Formula: see text] is obtained using the leptonic analyser and events in which at least two of the jets are tagged as b-quark jets. The fitted fractions of longitudinal, left- and right-handed polarisation states are [Formula: see text], [Formula: see text] and [Formula: see text], and are the most precisely measured W boson polarisation fractions to date. Limits on anomalous couplings of the Wtb vertex are set