An evaluation of the polymorphisms Ins16bp and Arg72Pro in p53 as breast cancer risk modifiers in BRCA1 and BRCA2 mutation carriers

The close functional relationship between p53 and the breast cancer susceptibility genes BRCA1 and BRCA2 has promoted the investigation of various polymorphisms in the p53 gene as possible risk modifiers in BRCA1/2 mutation carriers. Specifically, two polymorphisms in p53, c.97-147ins16bp and p.Arg72Pro have been analysed as putative breast cancer susceptibility variants, and it has been recently reported that a p53 haplotype combining the absence of the 16-bp insertion and the presence of proline at codon 72 (No Ins-72Pro) was associated with an earlier age at the onset of the first primary tumour in BRCA2 mutation carriers in the Spanish population. In this study, we have evaluated this association in a series of 2932 BRCA1/2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2

Chapter 13: Current Management and Treatment

The prevalence of heart failure (HF) is escalating rapidly, consuming significant healthcare resources, inflicts significant morbidity and mortality, and greatly impacts quality of life. Dilated cardiomyopathy (DCM) is a frequent cause of HF and is characterized by a progressive course. Nowadays pharmacological and non-pharmacological therapies have dramatically changed DCM\u2019s natural history. Familial screening program represents the first step in order to identify preclinic manifestation of DCM: first-degree relatives carrying a disease-causing mutation or without a clear genetic background must perform a periodic clinical and instrumental evaluation. Patients with a clinical diagnosis of HF and LV dysfunction should receive recommended therapies: beta-blockers (BB), ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB), aldosterone antagonists, and more recently angiotensin receptor-neprilysin inhibitor (ARNI) and ivabradine are established therapies for chronic HF. In case of persistent systolic dysfunction and/or severe intraventricular conduction delay, an ICD and/or CRT are indicated. Finally, heart transplantation and mechanical circulatory support (MCS) are options that can be used in critically ill HF who can\u2019t be stabilized by medical therapy alone