Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10− 8) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10− 4] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10− 9) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46–4.70, P = 4.8 × 10− 69). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction

Management development: a literature review and implications for future research – Part I: Conceptualisations and Practices

Interest in management development is mushrooming. The number of articles which address different aspects of it are likewise increasing apace. This has heightened the need for a broad-based review which will pull the material together, give shape to it, evaluate it and draw out its implications. In this, the first of a two-part article, this task is commenced

Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P &lt; 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P &lt; 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P &lt; 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction

Strange Hadron Spectroscopy with Secondary KL Beam in Hall D

Final version of the KLF Proposal [C12-19-001] approved by JLab PAC48. The intermediate version of the proposal was posted in arXiv:1707.05284 [hep-ex]. 103 pages, 52 figures, 8 tables, 324 references. Several typos were fixedWe propose to create a secondary beam of neutral kaons in Hall D at Jefferson Lab to be used with the GlueX experimental setup for strange hadron spectroscopy. The superior CEBAF electron beam will enable a flux on the order of $1\times 10^4~K_L/sec$, which exceeds the flux of that previously attained at SLAC by three orders of magnitude. The use of a deuteron target will provide first measurements ever with neutral kaons on neutrons. The experiment will measure both differential cross sections and self-analyzed polarizations of the produced $\Lambda$, $\Sigma$, $\Xi$, and $\Omega$ hyperons using the GlueX detector at the Jefferson Lab Hall D. The measurements will span CM $\cos\theta$ from $-0.95$ to 0.95 in the range W = 1490 MeV to 2500 MeV. The new data will significantly constrain the partial wave analyses and reduce model-dependent uncertainties in the extraction of the properties and pole positions of the strange hyperon resonances, and establish the orbitally excited multiplets in the spectra of the $\Xi$ and $\Omega$ hyperons. Comparison with the corresponding multiplets in the spectra of the charm and bottom hyperons will provide insight into he accuracy of QCD-based calculations over a large range of masses. The proposed facility will have a defining impact in the strange meson sector through measurements of the final state $K\pi$ system up to 2 GeV invariant mass. This will allow the determination of pole positions and widths of all relevant $K^\ast(K\pi)$ $S$-,$P$-,$D$-,$F$-, and $G$-wave resonances, settle the question of the existence or nonexistence of scalar meson $\kappa/K_0^\ast(700)$ and improve the constrains on their pole parameters. Subsequently improving our knowledge of the low-lying scalar nonet in general