Radon and childhood cancer

British Journal of Cancer (2002) 87, 1336–1337. doi:10.1038/sj.bjc.6600671 www.bjcancer.co

Vitamin K and childhood cancer: a population based case-control study in Lower Saxony, Germany.

OBJECTIVE--To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer. DESIGN--Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups. SETTING--State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry. SUBJECTS--272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex. MAIN EXPOSURE MEASURES--Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis. RESULTS--An association between parenteral vitamin K exposure and childhood cancer (leukaemias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model. CONCLUSIONS--This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer

Epidemiologische Studien zum Auftreten von Leukaemieerkrankungen bei Kindern in Deutschland

The recently published results demonstrate the information value of well-managed epidemiologic cancer registers: Based on comprehensive, differentiated incidence analyses alone, important information can be obtained which also is useful for public health policies. Further epidemiologic investigations of possible risk factors can be particularly effectively carried out taking the approach of case control studies as a starting point. A population-based cancer register offers an excellent methodological basis for this purpose. The results of a population-based case control study likewise are suitable data giving direct and valuable information on the situation of the entire population. This information can be applied to finally solve some of the questions of particular interest to the national population, as for instance the question of whether there is an increased risk of developing leukemia in the population living in the neighbourhood of nuclear installations in Germany. (Orig./CB)Die jetzt vorgelegten Studienergebnisse illustrieren die Aussagemoeglichkeiten gut funktionierender epidemiologischer Krebsregister: Bereits auf der Basis umfangreicher, differenzierter Inzidenzanalysen koennen wichtige Erkenntnisse gewonnen werden, die auch eine gesundheitspolitische Bedeutung haben. Weitergehende epidemiologische Untersuchungen moeglicher Risikofaktoren koennen besonders effektiv mit dem Ansatz der Fallkontrollstudien durchgefuehrt werden. Auch hierzu liefern ein bevoelkerungsbezogenes Krebsregister eine hervorragende methodische Grundlage. Weiterhin ist es moeglich, die Resultate einer Fallkontrollstudie, die im bevoelkerungsbezogenen Ansatz durchgefuehrt wird, unmittelbar fuer Aussagen zu verwenden, die fuer die Gesamtbevoelkerung Gueltigkeit besitzen. Damit koennen gewisse Fragestellungen, die zum Beispiel fuer die Oeffentlichkeit von besonderem Interesse sind, abschliessend beantwortet werden, wie es im jetzt vorliegenden Fall fuer die Frage nach Leukaemiehaeufungen in der Umgebung von kerntechnischen Anlagen in der Bundesrepublik geschieht. (orig./MG)SIGLEAvailable from TIB Hannover: RO 3190(489) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

HDAC7 regulates histone 3 lysine 27 acetylation and transcriptional activity at super-enhancer-associated genes in breast cancer stem cells

Chromatin regulation through histone modifications plays an essential role in coordinated expression of multiple genes. Alterations in chromatin induced by histone modifiers and readers regulate critical transcriptional programs involved in both normal development and tumor differentiation. Recently, we identified that histone deacetylases HDAC1 and HDAC7 are necessary to maintain cancer stem cells (CSCs) in both breast and ovarian tumors. Here, we sought to investigate the CSC-specific function of HDAC1 and HDAC7 mechanistically by using a stem-like breast cancer (BrCa) cell model BPLER and matched nonstem tumor cell (nsTC)-like HMLER, along with conventional BrCa cell lines with different CSC enrichment levels. We found that HDAC1 and HDAC3 inhibition or knockdown results in HDAC7 downregulation, which is associated with a decrease in histone 3 lysine 27 acetylation (H3K27ac) at transcription start sites (TSS) and super-enhancers (SEs) prominently in stem-like BrCa cells. Importantly, these changes in chromatin landscape also correlate with the repression of many SE-associated oncogenes, including c-MYC, CD44, CDKN1B, SLUG, VDR, SMAD3, VEGFA, and XBP1. In stem-like BrCa cells, HDAC7 binds near TSS and to SEs of these oncogenes where it appears to contribute to both H3K27ac and transcriptional regulation. These results suggest that HDAC7 inactivation, directly or through inhibition of HDAC1 and HDAC3, can result in the inhibition of the CSC phenotype by downregulating multiple SE-associated oncogenes. The CSC selective nature of this mechanism and the prospect of inhibiting multiple oncogenes simultaneously makes development of HDAC7 specific inhibitors a compelling objective