Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Background Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk

Breast cancer risk genes: association analysis in more than 113,000 women

BACKGROUNDGenetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.METHODSWe used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.RESULTSProtein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.CONCLUSIONSThe results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.)Molecular tumour pathology - and tumour geneticsMTG1 - Moleculaire genetica en pathologie van borstkanke

Structural Study of Carbon Coated TiO2 Anatase Nanoparticles as High Performance Anode Materials for Na Ion Batteries

In this work, we study the electronic and atomic structural modifications occurring in TiO2 anatase nanoparticles as anode materials in Na ion batteries upon sodiation and desodiation. The structural investigation is performed over both long and short range order by combining a comprehensive extended X ray absorption fine structure EXAFS characterization with X ray diffraction XRD . The evolution of the electronic structure upon cycling is qualitatively investigated by X ray absorption near edge structure XANES analysis. The goal of this work is to correlate the outstanding electrochemical performance of carbon coated TiO2 anatase nanoparticles in sodium batteries with the electronic and structural modifications induced during the sodiation and desodiation processes upon cycling. This work also demonstrates for the first time a coherent explanation of the structural changes observed, where an electrochemically induced short range ordering is revealed upon cyclin

The similarity renormalization group for three-body interactions in one dimension

We report on recent progress of the implementation of the similarity renormalization group (SRG) for three-body interactions in a one-dimensional, bosonic model system using the plane-wave basis. We discuss our implementation of the flow equations and show results that confirm that results in the three-body sector remain unchanged by the transformation of the Hamiltonian. We also show how the SRG transformation decouples low- from high-momentum nodes in the three-body sector and therefore simplifies the numerical calculation of observables

Antixenosis of bean genotypes to Chrysodeixis includens (Lepidoptera: Noctuidae)

The objective of this work was to evaluate bean genotypes for resistance to soybean looper (Chrysodeixis includens). Initially, free-choice tests were carried out with 59 genotypes, divided into three groups according to leaf color intensity (dark green, light green, and medium green), in order to evaluate oviposition preference. Subsequently, 12 genotypes with high potential for resistance were selected, as well as two susceptible commercial standards. With these genotypes, new tests were performed for oviposition in a greenhouse, besides tests for attractiveness and consumption under laboratory conditions (26 +/- 2 degrees C, 65 +/- 10% RH, and 14 h light: 10 h dark photophase). In the no-choice test with adults, in the greenhouse, the 'IAC Jabola', Arcelina 1, 'IAC Boreal', 'Flor de Mayo', and 'IAC Formoso'genotypes were the least oviposited, showing antixenosis-type resistance for oviposition. In the free-choice test with larvae, Arcelina 4, 'BRS Horizonte', 'Perola', H96A102-1-1-1-52, 'IAC Boreal', 'IAC Harmonia', and 'IAC Formoso'were the less consumed genotypes, which indicates antixenosis to feeding. In the no-choice test, all genotypes (except for 'IAPAR 57') expressed moderate levels of antixenosis to feeding against C. includens larvae.O objetivo deste trabalho foi avaliar genótipos de feijoeiro quanto à resistência a lagarta-falsa-medideira (Chrysodeixis includens). Inicialmente, foram realizados testes com chance de escolha com 59 genótipos, divididos em três grupos, de acordo com a intensidade de coloração das folhas (verde-escura, verde-clara e verde-médio), para avaliar a preferência quanto à oviposição. Em seguida, selecionaram-se 12 genótipos com grande potencial de resistência, assim como dois padrões comerciais suscetíveis. Com estes genótipos, realizaram-se novos ensaios de oviposição, em casa de vegetação, além de testes de atratividade e consumo, em condições de laboratório (26±2ºC, 65±10% UR e fotófase de 14 h luz: 10 h escuro). No teste sem chance de escolha, com adultos, em casa de vegetação, os genótipos 'IAC Jabola', Arcelina 1, 'IAC Boreal', 'Flor de Mayo' e 'IAC Formoso' foram os menos ovipositados, tendo apresentado resistência do tipo antixenose à oviposição. No teste com chance de escolha, com larvas, Arcelina 4, 'BRS Horizonte', 'Pérola', H96A102-1-1-1-52, 'IAC Boreal', 'IAC Harmonia' e 'IAC Formoso' foram os genótipos menos consumidos, o que indica antixenose à alimentação. No teste sem chance de escolha, todos os genótipos (exceto 'IAPAR 57') expressaram níveis moderados de antixenose à alimentação de larvas de C. includens.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq