Prediction of breast cancer risk based on profiling with common genetic variants

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

Value creation in capital waterway projects: Application of a transaction cost and transaction benefit framework for the Miami River and the New Orleans Inner Harbour Navigation Canal

Waterways have many more ties with society than as a medium for the transportation of goods alone. Waterway systems offer society many kinds of socio-economic value. Waterway authorities responsible for management and (re)development need to optimize the public benefits for the investments made. However, due to the many trade-offs in the system these agencies have multiple options for achieving this goal. Because they can invest resources in a great many different ways, they need a way to calculate the efficiency of the decisions they make. Transaction cost theory, and the analysis that goes with it, has emerged as an important means of justifying efficiency decisions in the economic arena. To improve our understanding of the value-creating and coordination problems for waterway authorities, such a framework is applied to this sector. This paper describes the findings for two cases, which reflect two common multi trade-off situations for waterway (re)development. Our first case study focuses on the Miami River, an urban revitalized waterway. The second case describes the Inner Harbour Navigation Canal in New Orleans, a canal and lock in an industrialized zone, in need of an upgrade to keep pace with market developments. The transaction cost framework appears to be useful in exposing a wide variety of value-creating opportunities and the resistances that come with it. These insights can offer infrastructure managers guidance on how to seize these opportunities.