Tratado de derechos reales. Tomo II Propiedad y posesión

La presente investigación está referida al análisis de los dos principales derechos reales: la posesión y la propiedad, y es la continuación de la investigación concluida denominada Tratado de derechos reales, tomo I, teoría de los bienes y los derechos reales. Esta parte de la investigación corresponde al desarrollo de dos de sus principales instituciones. Así, se comienza con el análisis sociojurídico de la posesión (poder hecho) como derecho transitorio (temporal y momentáneo), para luego entrar al desarrollo de la propiedad (poder de derecho) como derecho definitivo (permanente y total), ambas instituciones reconocidas como situaciones jurídicas de gran trascendencia en las relaciones jurídicas patrimoniales, protegidas por la ley a través de mecanismos de defensa

The Use of Antihypertensive Medication and the Risk of Breast Cancer in a Case-Control Study in a Spanish Population: The MCC-Spain Study

INTRODUCTION: The evidence on the relationship between breast cancer and different types of antihypertensive drugs taken for at least 5 years is limited and inconsistent. Furthermore, the debate has recently been fueled again with new data reporting an increased risk of breast cancer among women with a long history of use of antihypertensive drugs compared with nonusers. METHODS: In this case-control study, we report the antihypertensive drugs-breast cancer relationship in 1,736 breast cancer cases and 1,895 healthy controls; results are reported stratifying by the women's characteristics (i.e., menopausal status or body mass index category) tumor characteristics and length of use of antihypertensive drugs. RESULTS: The relationship among breast cancer and use of calcium channel blockers (CCB) for 5 or more years had odds ratio (OR) = 1.77 (95% CI, 0.99 to 3.17). Stratifying by BMI, the OR increased significantly in the group with BMI ≥ 25 (OR 2.54, 95% CI, 1.24 to 5.22). CCBs were even more strongly associated with more aggressive tumors, (OR for invasive tumors = 1.96, 95% CI = 1.09 to 3.53; OR for non ductal cancers = 3.97, 95% CI = 1.73 to 9.05; OR for Erbb2+ cancer = 2.97, 95% CI: 1.20 to 7.32). On the other hand, premenopausal women were the only group in which angiotensin II receptor blockers may be associated with breast cancer (OR = 4.27, 95% CI = 1.32 to 13.84) but this could not be identified with any type or stage. Use of angiotensin-converting-enzyme inhibitors, beta blockers and diuretics were not associated with risk. CONCLUSIONS: In this large population-based study we found that long term use of calcium channel blockers is associated with some subtypes of breast cancer (and with breast cancer in overweight women)

Role of circulating MicroRNAs in prostate cancer diagnosis and risk stratification in the MCC Spain study

To identify circulating microRNAs (miRNAs) associated with prostate cancer and to develop predictive models capable of distinguishing cases from controls and stratifying patients by Gleason risk categories (low, intermediate, and high risk). This case-control study included 203 prostate cancer cases and 54 population-based controls. Serum samples were analyzed by RT-qPCR (performed at QIAGEN Genomic Services). Total RNA was extracted from 200 µl of serum using the miRNeasy Serum/Plasma Advanced Kit and reverse-transcribed with the miRCURY LNA RT Kit. A panel of 46 candidate miRNAs was profiled, and feature selection was performed using LASSO penalization. Logistic regression models were used to estimate age- and covariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the association between miRNA expression and prostate cancer risk. Predictive performance was assessed using repeated 5-fold cross-validation with bootstrap resampling (10 repetitions; 1000 resamples), and summarized using the area under the receiver operating characteristic curve (AUC) with bias-corrected 95% CIs. Fourteen miRNAs were significantly associated with prostate cancer. Notably, miR-199a-5p (OR = 1.89, 95% CI: 1.13-3.15; p = 0.015) and miR-150-5p (OR = 0.20, 95% CI: 0.06-0.63; p = 0.006) showed consistent differential expression across all Gleason risk categories, with miR-199a-5p overexpressed and miR-150-5p underexpressed, suggesting a potential role in disease progression. miR-145-5p, miR-182-5p, and miR-93-5p were significantly associated with prostate cancer in both the overall model and in low- and intermediate-risk strata, highlighting their potential relevance in early-stage disease. In contrast, miR-24-3p was exclusively overexpressed in high-risk prostate cancer (OR = 2.93, 95% CI: 1.43-5.98; p = 0.003), indicating a possible link with aggressive tumor phenotypes. Predictive models demonstrated strong discriminatory performance, particularly for the low-risk group (AUC = 0.930, 95% CI: 0.882-0.979), followed by the intermediate-risk (AUC = 0.806, 95% CI: 0.728-0.883) and high-risk groups (AUC = 0.752, 95% CI: 0.658-0.848). The overall model achieved an AUC of 0.824 (95% CI: 0.756-0.892), reflecting robust performance in distinguishing cases from controls. This study identifies key circulating miRNAs associated with prostate cancer and demonstrates their potential in predictive models for risk stratification. The strongest discriminatory performance was observed in low-risk tumors (AUC = 0.930), followed by intermediate- (AUC = 0.806) and high-risk (AUC = 0.752) categories. These findings support the use of miRNAs as non-invasive biomarkers for diagnosis and personalized management of prostate cancer.Funding: This study was partially funded by the “Accion Transversal del Cancer,” approved on the Spanish Ministry Council on the 11 October 2007, Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01889, PI11/02213, PI12/00488, PI12/01270, PI12/00715, PI14/01219, PI14/0613, PI17/01388 and PI18/00171), Fundación Marqués de Valdecilla (API 10/09), the ICGC International Cancer Genome Consortium CLL [The ICGC CLL-Genome Project was funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)], the Junta de Castilla y León (LE22 A10-2), the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, and salud201200057018 tra), the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), the Recercaixa (2010 ACUP 00310), the Regional Government of the Basque Country, the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government—Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850, the Fundación Caja de Ahorros de Asturias, and the University of Oviedo. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. AP-C was supported by the MINECO (Ministry of Economy in Spain) Grant no. PRE2019-089038, fellowship. Acknowledgements: Some samples included in this study were provided by the Basque Biobank www.biobancovasco.org and the Biobanco La Fe (B.0000723) and they were processed following standard operation procedures with the appropriate approval of the Ethical and Scientific Committees

Risk model for prostate cancer using environmental and genetic factors in the spanish multi-case-control (MCC) study

Prostate cancer (PCa) is the second most common cancer among men worldwide. Its etiology remains largely unknown compared to other common cancers. We have developed a risk stratification model combining environmental factors with family history and genetic susceptibility. 818 PCa cases and 1,006 healthy controls were compared. Subjects were interviewed on major lifestyle factors and family history. Fifty-six PCa susceptibility SNPs were genotyped. Risk models based on logistic regression were developed to combine environmental factors, family history and a genetic risk score. In the whole model, compared with subjects with low risk (reference category, decile 1), those carrying an intermediate risk (decile 5) had a 265% increase in PCa risk (OR = 3.65, 95% CI 2.26 to 5.91). The genetic risk score had an area under the ROC curve (AUROC) of 0.66 (95% CI 0.63 to 0.68). When adding the environmental score and family history to the genetic risk score, the AUROC increased by 0.05, reaching 0.71 (95% CI 0.69 to 0.74). Genetic susceptibility has a stronger risk value of the prediction that modifiable risk factors. While the added value of each SNP is small, the combination of 56 SNPs adds to the predictive ability of the risk model

Dietary zinc and risk of prostate cancer in Spain: MCC-Spain study

Zinc is a key trace element in normal prostate cell metabolism, and is decreased in neoplastic cells. However, the association between dietary zinc and prostate cancer (PC) in epidemiologic studies is a conflicting one. Our aim was to explore this association in an MCC-Spain case-control study, considering tumor aggressiveness and extension, as well as genetic susceptibility to PC. 733 incident cases and 1228 population-based controls were included for this study. Dietary zinc was assessed using a food frequency questionnaire, and genetic susceptibility was assessed with a single nucleotide polymorphisms (SNP)-based polygenic risk score (PRS). The association between zinc intake and PC was evaluated with mixed logistic and multinomial regression models. They showed an increased risk of PC in those with higher intake of zinc (Odds Ratio (OR) tertile 3vs1: 1.39; 95% Confidence interval (CI):1.00–1.95). This association was mainly observed in low grade PC (Gleason = 6 RRR tertile 3vs1: 1.76; 95% CI:1.18–2.63) as well as in localized tumors (cT1-cT2a RRR tertile 3vs1: 1.40; 95% CI:1.00–1.95) and among those with higher PRS (OR tertile 3vs1: 1.50; 95% CI:0.89–2.53). In conclusion, a higher dietary zinc intake could increase the risk of low grade and localized tumors. Men with higher genetic susceptibility might also have a higher risk of PC associated with this nutrient intake.Funding: The study was supported by the “Acción Transversal del Cáncer”, approved on the Spanish Ministry Council on the 11 October 2007, by the Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), by the Instituto de Salud Carlos III grants, co-funded by FEDER funds -a way to build EuropePI08/1770, PI09/0773, PI12/00715, PI09/1903,PI09/2078; PI09/1662; PI11/01403; PI12/00150; PI12/00488; PI15/00914; PI17CIII_00034;by the Fundación Marqués de Valdecilla grant API 10/09, by the Consejería de Salud of the Junta de Andalucía grant 2009-S0143, by the Conselleria de Sanitat of the Generalitat Valenciana grant AP061/10, by the Regional Government of the Basque Country, by the Fundación Caja de Ahorros de Asturias, by the University of Oviedo and by the Spanish Ministry of Economy and Competitiveness Juan de la Cierva de Incorporación grant IJCI-2014-20900

Serum 25-hydroxyvitamin D and breast cancer risk by pathological subtype (MCC-Spain)

Epidemiologic evidence on the association between vitamin D and breast cancer is still inconclusive. This study analyzes the association between serum 25-hydroxyvitamin D (25(OH)D) and breast cancer risk by pathologic subtype, stage at diagnosis and specific breast cancer risk factors. We conducted a population-based multicase-control study where 546 histologically-confirmed breast cancer cases and 558 population controls, frequently matched by geographic area, age and body mass index, were recruited in 12 Spanish provinces (MCC-Spain). Information was collected by a questionnaire and plasma 25(OH)D was measured by solid-phase extraction on-line coupled to liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS). Odds ratios and 95% confidence intervals were calculated using logistic and multinomial mixed regression models. We found a clear protective effect between 25(OH)D levels and breast cancer risk, with a significant dose-response trend (OR per 10?nmol/L?=?0.88; 95%CI?=?0.82-0.94). While no differences were observed between pre and postmenopausal women, stage at diagnosis, or across strata of the main breast cancer risk factors, the protection was more pronounced for triple negative tumors (OR per 10?nmol/L?=?0.64; p-heterogeneity?=?0.038). Similar results were observed when only cases sampled in the first month after diagnosis were considered. The protective effect of vitamin D on breast cancer risk may be subtype specific, being stronger for more aggressive tumors, which provides a new approach to prevent this disease.The study was funded by Carlos III Institute of Health grants (PI12/00488, PI12/00265, PI12/00715, PI12/01270, PI09/00773 and PI08/1770), by the Spanish Ministry of Health (EC11-273), by the Spanish Ministry of Economy and Competitiveness (IJCI-2014-20900) and by Consejería de Salud de la Junta de Andalucía (PI-0571-2009) competitive calls including peer review for scientific quality. Additional funding was provided by the Spanish Federation of Breast Cancer Patients (FECMA: EPY 1169-10), the Association of Women with Breast Cancer from Elche (AMACMEC: EPY 1394/15), the Marqués de Valdecilla foundation (grant API 10/09), and by Acción Transversal del Cancer, approved by the Spanish Ministry Council on October 11, 2007. None of the funders played any role in conducting research or writing the paper. This article presents independent research. The views expressed are those of the authors and not necessarily those of the Carlos III Institute of Health

Prostate cancer genetic propensity risk score may modify the association between this tumour and type 2 diabetes mellitus (MCC-Spain study)

Background: Some studies have reported an inverse association between type 2 diabetes mellitus (T2DM) and prostate cancer (PCa), but results on this issue are still inconsistent. In this study, we evaluate whether this heterogeneity might be related to differences in this relationship by tumour or by individual genetic susceptibility to PCa. Methods: We studied 1047 incident PCa cases and 1379 randomly selected controls, recruited in 7 Spanish provinces for the population-based MCC-Spain case-control. Tumour were classified by aggressiveness according to the International Society of Urological Pathology (ISUP), and we constructed a PCa polygenic risk score (PRS) as proxy for genetic susceptibility. The epidemiological questionnaire collected detailed self-reported data on T2DM diagnosis and treatment. The association between T2DM status and PCa was studied by fitting mixed logistic regression models, and, for its association by aggressiveness of PCa, with multinomial logistic regression models. To evaluate the possible modulator role of PRS in this relationship, we included the corresponding interaction term in the model, and repeated the analysis stratified by PRS tertiles. Results: Globally, our results showed an inverse association between T2DM and overall PCa limited to grade 1 tumours (ORISUP = 1: 0.72; 95% CI: 0.53-0.98), which could be compatible with a detection bias. However, PCa risk also varied with duration of diabetes treatment -inversely to metformin and positively with insulin-, without differences by aggressiveness. When we considered genetic susceptibility, T2DM was more strongly associated with lower PCa risk in those with lower PRS (ORtertile 1: 0.31; 95% CI: 0.11-0.87), independently of ISUP grade. Conclusions: Our findings reinforce the need to include aggressiveness and susceptibility of PCa, and T2DM treatments in the study of the relationship between both diseases

Burden of postmenopausal breast cancer attributable to excess body weight: comparative study of body mass index and CUN-BAE in MCC-Spain study

Background: 10% of postmenopausal breast cancer cases are attributed to a high body mass index (BMI). BMI underestimates body fat, particularly in older women, and therefore the cancer burden attributable to obesity may be even higher. However, this is not clear. CUN-BAE (Clínica Universidad de Navarra-Body Adiposity Estimator) is an accurate validated estimator of body fat, taking into account sex and age. The objective of this study was to compare the burden of postmenopausal breast cancer attributable to excess body fat calculated using BMI and CUN-BAE. Methods: This case-control study included 1033 cases of breast cancer and 1143 postmenopausal population controls from the multicase-control MCC-Spain study. Logistic regression models were used to calculate odds ratios (ORs). The population attributable fraction (PAF) of excess weight related to breast cancer was estimated with both anthropometric measures. Stratified analyses were carried out for hormone receptor type. Results: Excess body weight attributable to the risk of breast cancer was 23.0% when assessed using a BMI value ≥30 kg/m2 and 38.0% when assessed using a CUN-BAE value of ≥40% body fat. Hormone receptor stratification showed that these differences in PAFs were only observed in hormone receptor positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE. Conclusion: These findings suggest that the significance of excess body fat in postmenopausal hormone receptor positive breast cancer could be underestimated when assessed using only BMI. Accurate estimation of the cancer burden attributable to obesity is crucial for planning effective prevention initiatives

Cohort profile: the MCC-Spain follow-up on colorectal, breast and prostate cancers: study design and initial results

PURPOSE: Since 2016, the multicase-control study in Spain (MCC-Spain) has focused towards the identification of factors associated with cancer prognosis. Inception cohorts of patients with colorectal, breast and prostate cancers were assembled using the incident cases originally recruited. PARTICIPANTS: 2140 new cases of colorectal cancer, 1732 of breast cancer and 1112 of prostate cancer were initially recruited in 12 Spanish provinces; all cancers were incident and pathologically confirmed. Follow-up was obtained for 2097 (98%), 1685 (97%) and 1055 (94.9%) patients, respectively. FINDINGS TO DATE: Information gathered at recruitment included sociodemographic factors, medical history, lifestyle and environmental exposures. Biological samples were obtained, and 80% of patients were genotyped using a commercial exome array. The follow-up was performed by (1) reviewing medical records; (2) interviewing the patients by phone on quality of life; and (3) verifying vital status and cause of death in the Spanish National Death Index. Ninety-seven per cent of recruited patients were successfully followed up in 2017 or 2018; patient-years of follow-up were 30 914. Most colorectal cancers (52%) were at clinical stage II or lower at recruitment; 819 patients died in the follow-up and the 5-year survival was better for women (74.4%) than men (70.0%). 71% of breast cancers were diagnosed at stages I or II; 206 women with breast cancer died in the follow-up and the 5-year survival was 90.7%. 49% of prostate cancers were diagnosed at stage II and 32% at stage III; 119 patients with prostate cancer died in the follow-up and the 5-year survival was 93.7%. FUTURE PLANS: MCC-Spain has built three prospective cohorts on highly frequent cancers across Spain, allowing to investigate socioeconomic, clinical, lifestyle, environmental and genetic variables as putative prognosis factors determining survival of patients of the three cancers and the inter-relationship of these factors

Real-world experience with bezlotoxumab for prevention of recurrence of Clostridioides difficile infection

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI