23 research outputs found
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
SELF-DIFFUSION IN GAMMA URANIUM
The self-diffusion coefficient or uranium was measured at four temperatures in the gamma phase. The data are fitted by an Arrhenius-tyoe equation D = 2.33 x well with previously reported results. The value of D/sub o/ is lower than that predicted by Zener's theory, and the activation energy is much less than the value expected from various empirical codelations. (auth
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Bulk-assay calorimeter: Part 1. System design and operation. Part 2. Calibration and testing
The Bulk-Assay Calorimeter is designed to measure the thermal power emitted by plutonium-containing samples. The sample power range of the instrument is 1.4 to 22.4 W. The instrument package consists of the calorimeter measurement chamber, the control circuit power bin, and the data acquisition system. Two sample preheating chambers and five calorimeter canisters for containing the samples are included. A set of 32 test points which monitor voltages at points within the calorimeter and its control circuitry are accessed by the data acquisition system. The use of the test points is described. System start-up and checkout are described. Sample assay and preheater operation procedures are given. The data acquisition system and data analysis software are described. The calorimeter was calibrated at 23 points with heat sources from 1.4 to 22.4 watts. The combined measurement error varied with sample power from 1.4% to 0.1% over the range of calibration measurements. Circuit diagrams for the calorimeter and schematics for the data acquisition system are included. (LEW