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Biobanks play an important role in biomedical research that aims to understand cellular and molecular mechanisms underlying the development of diseases, and to improve interventions for human health. Despite financial support from mixed public funding streams, long-term sustainability of public biobanks remains a major concern. Review of the literature demonstrates that total cost-recovery strategies, as well as commercialization of research results or derived products, may not represent the best way to reach and maintain sustainability. Public biobanks require support by long-term investment and commitment from public and governmental sources, as well as support from industrial users. In this regard, this study suggests strategies to improve long-term sustainability, such as sample-sharing and biobank consolidation to reduce unit costs, embedding public biobanks in health care systems, and working to implement global funding mechanisms.

A disease risk model is a statistical method which assesses the probability that an individual will develop one or more diseases within a stated period of time. Such models take into account the presence or absence of specific epidemiological risk factors associated with the disease and thereby potentially identify individuals at higher risk. Such models are currently used clinically to identify people at higher risk, including identifying women who are at increased risk of developing breast cancer. Many genetic and non-genetic breast cancer risk models have been developed previously. We have evaluated existing non-genetic/non-clinical models for breast cancer that incorporate modifiable risk factors. This review focuses on risk models that can be used by women themselves in the community in the absence of clinical risk factors characterization. The inclusion of modifiable factors in these models means that they can be used to improve primary prevention and health education pertinent for breast cancer. Literature searches were conducted using PubMed, ScienceDirect and the Cochrane Database of Systematic Reviews. Fourteen studies were eligible for review with sample sizes ranging from 654 to 248,407 participants. All models reviewed had acceptable calibration measures, with expected/observed (E/O) ratios ranging from 0.79 to 1.17. However, discrimination measures were variable across studies with concordance statistics (C-statistics) ranging from 0.56 to 0.89. We conclude that breast cancer risk models that include modifiable risk factors have been well calibrated but have less ability to discriminate. The latter may be a consequence of the omission of some significant risk factors in the models or from applying models to studies with limited sample sizes. More importantly, external validation is missing for most of the models. Generalization across models is also problematic as some variables may not be considered applicable to some populations and each model performance is conditioned by particular population characteristics. In conclusion, it is clear that there is still a need to develop a more reliable model for estimating breast cancer risk which has a good calibration, ability to accurately discriminate high risk and with better generalizability across populations.

The structure and expression of the human Rad53 homologue Chk2 was analysed in breast cancer. The previously described silent polymorphism at nucleotide 252 in codon 84 (GAA>GAG) was observed in 5/141 cases. Somatic Chk2 coding mutations were detected in 7/141 cases, these occurring in 4/18 BRCA1-associated breast cancers, 1/78 sporadic breast cancers and 2/25 typical medullary carcinomas. Each of the BRCA1-associated cancers with Chk2 mutations also contained mutations in p53, whereas the single sporadic cancer with Chk2 mutation was wild-type for p53. Expression of Chk2 was ubiquitously detected in normal ductal epithelium of the breast, but there was loss of expression in a significant proportion of breast carcinomas, and this occurred in cancers both with and without p53 mutation. A CpG island was identified 5' of the Chk2 transcriptional start site, but there was no evidence of cytosine methylation in any of the cancers with down-regulated Chk2 expression. Analysis of the germ-line of 45 individuals with hereditary or early onset breast cancer revealed wild-type Chk2 sequence in all cases. Thus, despite the rarity of somatic mutations in Chk2 in sporadic breast carcinomas, our results nevertheless reveal that concomitant loss of function in Chk2 (via down-regulation of expression) and p53 (via mutation) occurs in a proportion of sporadic cases. However, consistent with other studies, we show that germ-line mutations in Chk2 are unlikely to account for a significant proportion of non BRCA1-, non BRCA2-associated hereditary breast cancers.

Background There is little confidence in the consistency of estimation of DNA concentrations when samples move between laboratories. Evidence on this consistency is largely anecdotal. Therefore there is a need first to measure this consistency among different laboratories and then identify and implement remedies. A pilot experiment to test logistics and provide initial data on consistency was therefore conceived. Methods DNA aliquots at nominal concentrations between 10 and 300 ng/μl were dispensed into the wells of 96-well plates by one participant - the coordinating centre. Participants estimated the concentration in each well and returned estimates to the coordinating centre. Results Considerable overall variability was observed among estimates. There were statistically significant differences between participants' measurements and between fluorescence emission and absorption spectroscopy. Conclusion Anecdotal evidence of variability in DNA concentration estimation has been substantiated. Reduction in variability between participants will require the identification of major sources of variation, specification of effective remedies and their implementation.