The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.

Purpose To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.Methods We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk.Results For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC 313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively.Conclusion The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making

Nanotechnology Applications to Improve Solubility of Bioactive Constituents of Foods for Health-Promoting Purposes

Foods-derived multifunctional compounds, such as carotenoids, vitamins, phytosterols, polyunsaturated lipids, curcuminoids, flavonoids and polyphenols, in addition to the basic nutritional value, own extra health benefits and are considered \u201cpharmaceutical-grade nutrients\u201d better known as \u201dnutraceuticals\u201d. Similarly, phytochemicals from plants, characterized by analogous chemical structures, can be considered \u201cpharmaceutical-grade molecules\u201d. They could provide both diseases preventive actions and remarkable therapeutic benefits but, the efforts for identifying their mode of action and for applying them into food industry with health-promoting purposes, are often unsuccessful. Solubility is essential for a good absorption in the gastrointestinal tract and to achieve the systemic concentration necessary for an effective therapeutic activity, but the majority of these compounds are water-insoluble. Consequently, when ingested, they encounter many difficulties in crossing the diverse barriers to reach the bloodstream and to distribute to cells and tissues. Their absorption at gastric or intestinal level is troubled and in addition, they suffer from early degradation or fast metabolism, so rarely they manage to reach the site of action in therapeutically effective concentration and their clinical applications result strongly limited. Toxic excipients and harmful solubilizing agents were and are extensively used for solubilizing and delivering non-soluble bioactive chemicals (BACs) despite the resulting unpleasant side effects complained of by patients. During last decades, several new techniques, often resorting to nanotechnology, aiming at enhancing BACs solubility, at solving their pharmacokinetics drawbacks, at avoiding their early inactivation or fast metabolism, have been developed. On this background, the following chapter provides an overview concerning nanotechnology contribute and its technological advancements in \u201cmanufacturing\u201d nutraceuticals and phytochemicals in more bioavailable nanoparticles. In addition, it is reviewed the involvement of nanoscience in developing and enhancing food-grade solid nanosized materials to be used as BACs \u201ccontainers\u201d and \u201cvehicles\u201d either for their safe and effective oral administration, in the frame of medical treatments, or for achieving smart food ingredients to improve the quality and shelf life of nourishments