25 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
Thromboprophylaxis with a low molecular weight heparin (tinzaparin) in emergency abdominal surgery. A double-blind multicenter trial
In this prospective randomized double-blind study the thromboprophylactic effect of postoperative low molecular weight heparin (tinzaparin) was compared with placebo in 80 patients undergoing emergency abdominal surgery. The fibrinogen uptake test was used but because of withdrawal of the labelled fibrinogen from the market the calculated number of patients was not reached. However, this is one of the few studies in emergency abdominal surgery we thought it important to report. The frequency of deep vein thrombosis was reduced with prophylaxis from 22% (95% conf. intervall 11-38%) to 8% (2-21%), a risk reduction of 65%, which is however not significant. Together with data from the few previously published studies it can be concluded that patients undergoing emergency abdominal surgery seem to benefit from prophylaxis, which should be instituted either before operation or at latest 24 hours after. The exact prophylactic relation between pre- and post-operative start would, however, require a separate, randomized study
Effect of the cytokines on the prostaglandin E2 synthesis by lens epithelial cells of human cataracts.
Modelagem e simulação de redes de comunicação baseadas no protocolo CAN - Controller Area Network
COMPLEXO: identifying the missing heritability of breast cancer via next generation collaboration
MTG1 - Moleculaire genetica en pathologie van borstkanke