Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.UK funding includes Cancer Research UK and NIH.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-016-0718-

A national policy on asthma management for schools

Since asthma is the most common chronic illness in childhood, many of the problems associated with this condition will impact on the child's education. Because of widespread concerns regarding the management of asthma in schools, a subcommittee of the Thoracic Society of Australia and New Zealand, Asthma Special Interest Group, was convened to draw up national guidelines for school staff in order to provide optimal management of asthma in the school setting. We used current medical literature and the clinical experience of the authors who have dealt with children and adolescents suffering from asthma in the hospital, community and school environment. A number of issues had been identified, including; the availability of an asthma first aid kit; correct use of bronchodilator aerosols by puffer and spacer devices; and clear instructions as to when to notify parents and when to call an ambulance to the school. To provide optimal care of asthma in the school setting, the committee made the following recommendations: (i) improved guidance and training of school teachers and ancillary staff in appropriate asthma care; (ii) improved recognition by schools of those students with asthma; (iii) schools should encourage a policy of exercise for all students with asthma; (iv) asthma medication should be readily available at all times to those students with asthma; (v) the safety of school excursions and school camps should be improved by having available personnel competent in acute asthma management; a mobile asthma first aid kit; and by ensuring the student continues taking their usual asthma medications throughout the excursion; (vi) the early introduction of a 'lung health' education programme for all students, with particular emphasis on asthma being encouraged. We believe that asthma management in schools would be optimized if this national policy were adopted throughout Australian schools