Temporal evolution of brain cancer incidence in the municipalities of Navarre and the Basque Country, Spain

Background: Brain cancer incidence rates in Spain are below the European’s average. However, there are two regions in the north of the country, Navarre and the Basque Country, ranked among the European regions with the highest incidence rates for both males and females. Our objective here was two-fold. Firstly, to describe the temporal evolution of the geographical pattern of brain cancer incidence in Navarre and the Basque Country, and secondly, to look for specific high risk areas (municipalities) within these two regions in the study period (1986–2008). Methods: A mixed Poisson model with two levels of spatial effects is used. The model also included two levels of spatial effects (municipalities and local health areas). Model fitting was carried out using penalized quasi-likelihood. High risk regions were detected using upper one-sided confidence intervals. Results: Results revealed a group of high risk areas surrounding Pamplona, the capital city of Navarre, and a few municipalities with significant high risks in the northern part of the region, specifically in the border between Navarre and the Basque Country (Gipuzkoa). The global temporal trend was found to be increasing. Differences were also observed among specific risk evolutions in certain municipalities. Conclusions: Brain cancer incidence in Navarre and the Basque Country (Spain) is still increasing with time. The number of high risk areas within those two regions is also increasing. Our study highlights the need of continuous surveillance of this cancer in the areas of high risk. However, due to the low percentage of cases explained by the known risk factors, primary prevention should be applied as a general recommendation in these populations.This research has been supported by the Spanish Ministry of Science and Innovation (project MTM 2011-22664, jointly sponsored with FEDER grants and project MTM2014-51992-R), and by the Health Department of the Navarre Government (project 113, Res.2186/2014)

Association Between Egg Consumption and Dementia Risk in the EPIC-Spain Dementia Cohort

Current evidence suggests that egg composition might have potential neuroprotective effects. Our aim was to determine the association between egg consumption and the risk of dementia in a Mediterranean population. MethodsThis study was carried out in 3 centers from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort, i.e., 25,015 participants aged 30-70 years, recruited in 1992-1996, and followed up for a mean of 21.5 years. ResultsA total of 774 incident dementia cases were diagnosed and validated, of which 518 were Alzheimer's disease (AD). Data on egg consumption were estimated using a validated dietary history questionnaire at recruitment. Cox proportional hazards models, adjusted for confounders, were used in the analyses. No association was observed between egg consumption and either total dementia [hazard ratio between extreme quartiles (HRQ4vs.Q1: 1.05; 95% CI 0.85-1.31; p-trend = 0.93)] or AD (HRQ4vs.Q1 0.93; 95% CI 0.72-1.21; p-trend = 0.50) risks. After dividing the population by adherence to the relative Mediterranean diet (rMED) score, a borderline inverse association was found between egg intake and both total dementia (HRQ4vs.Q1: 0.52; 95% CI 0.30-0.90; p-trend = 0.10) and AD (HRQ4vs.Q1: 0.52; 95% CI 0.27-1.01; p-trend = 0.13) risks within participants with low adherence to rMED score. However, no association was observed in participants with medium and high adherence to rMED score. ConclusionThis prospective study suggests that egg consumption is associated with a reduced risk of dementia, and specifically of AD, in the adult population with low adherence to rMED score; whereas it has no impact in subjects with moderate and high MD adherence

A Set of Reliable Samples for the Study of Biomarkers for the Early Diagnosis of Parkinson's Disease

BackgroundParkinson's disease (PD) is a progressive neurodegenerative disorder, diagnosed according to the clinical criteria that occur in already advanced stages of PD. The definition of biomarkers for the early diagnosis of PD represents a challenge that might improve treatment and avoid complications in this disease. Therefore, we propose a set of reliable samples for the identification of altered metabolites to find potential prognostic biomarkers for early PD. MethodsThis case-control study included plasma samples of 12 patients with PD and 21 control subjects, from the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC)-Navarra cohort, part of the EPIC-Spain study. All the case samples were provided by healthy volunteers who were followed-up for 15.9 (+/- 4.1) years and developed PD disease later on, after the sample collection. Liquid chromatography coupled to tandem mass spectrometry was used for the analysis of samples. ResultsOut of 40 that were selected and studied due to their involvement in established cases of PD, seven significantly different metabolites between PD cases and healthy control subjects were obtained in this study (benzoic acid, palmitic acid, oleic acid, stearic acid, myo-inositol, sorbitol, and quinolinic acid). These metabolites are related to mitochondrial dysfunction, the oxidative stress, and the mechanisms of energy production. ConclusionWe propose the samples from the EPIC study as reliable and invaluable samples for the search of early biomarkers of PD. Likewise, this study might also be a starting point in the establishment of a well-founded panel of metabolites that can be used for the early detection of this disease.he EPIC study received financial support from the International Agency for Research on Cancer (AEP/93/06), the European Commission (SO-97-200302-05F02 and SP23-CT-2005-006438), the Health Research Fund (FIS) of the Spanish Ministry of Health, the Red Temática de Investigación Cooperativa de Centros de Cáncer (RTICCC C03/10 and RD06/0020), the Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), the participating Regional Governments of Andalusia, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (ICO). This study was furthermore supported by the Ministry of Health of the Basque Government, Exp 20161109

Cytogenetic analysis of 280 patients with multiple myeloma and related disorders: primary breakpoints and clinical correlations

Cytogenetic analysis of unstimulated short-term bone marrow cell cultures was performed on 280 patients with multiple myeloma and related disorders. In 65% of the cases, an additional short term B-cell stimulated culture was also examined. Chromosomally abnormal clones were found in 31% of the patients, 15% in Waldenström macroglobulinemia. 25% in monoclonal gammopathies, 33% in multiple myeloma, and 50% in plasma cell leukemia. Three primary chromosomal breakpoints were recurrently involved: 14q32, 16q22, and 22q11. Structural rearrangements of chromosome 1 were the most frequent (26% of the abnormal cases), but always as a secondary change. Rearrangements of band 14q32 were found in 22% of the abnormal cases. Among the multiple myeloma patients who showed an abnormal karyotype, 33 (46%) were hyperdiploid, most frequently, with 52-56 chromosomes, 29 patients (40%) were pseudodiploid, and the remaining 12 cases (14%) were hypodiploid. A highly significant relation was observed between the presence of an abnormal karyotype and the following clinical parameters: stage III (P = 0.0001), bone marrow plasma cell infiltration greater than 30% (P = 0.0001), presence of bone lesions (P = 0.0009), and beta 2-microglobulin levels greater than 4 mg/L (P = 0.0001)

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

Comparative genomic hybridization and amplotyping by arbitrarily primed PCR in stage A B-CLL

Cytogenetic analysis is useful in the diagnosis and to assess prognosis of B-cell chronic lymphocytic leukemia (B-CLL). However, successful cytogenetics by standard techniques has been hindered by the low in vitro mitotic activity of the malignant B-cell population. Fluorescence in situ hybridization (FISH) has become a useful tool, but it does not provide an overall view of the aberrations. To overcome this hurdle, two DNA-based techniques have been tested in the present study: comparative genomic hybridization (CGH) and amplotyping by arbitrarily primed PCR (AP-PCR). Comparative genomic hybridization resolution depends upon the 400-bands of the human standard karyotype. AP-PCR allows detection of allelic losses and gains in tumor cells by PCR fingerprinting, thus its resolution is at the molecular level. Both techniques were performed in 23 patients with stage A B-CLL at diagnosis. The results were compared with FISH. The sensitivity of AP-PCR was greater than CGH (62% vs. 43%). The use of CGH combined with AP-PCR allowed to detect genetic abnormalities in 79% (15/19) of patients in whom G-banding was not informative, providing a global view of the aberrations in a sole experiment. This study shows that combining these two methods with FISH, makes possible a more precise genetic characterization of patients with B-CLL

Amplification of IGH/MYC fusion in clinically aggressive IGH/BCL2-positive germinal center B-cell lymphomas

Activation of an oncogene via its juxtaposition to the IGH locus by a chromosomal translocation or, less frequently, by genomic amplification is considered a major mechanism of B-cell lymphomagenesis. However, amplification of an IGH/oncogene fusion, coined a complicon, is a rare event in human cancers and has been associated with poor outcome and resistance to treatment. In this article are descriptions of two cases of germinal-center-derived B-cell lymphomas with IGH/BCL2 fusion that additionally displayed amplification of an IGH/MYC fusion. As shown by fluorescence in situ hybridization, the first case contained a IGH/MYC complicon in double minutes, whereas the second case showed a BCL2/IGH/MYC complicon on a der(8)t(8;14)t(14;18). Additional molecular cytogenetic and mutation analyses revealed that the first case also contained a chromosomal translocation affecting the BCL6 oncogene and a biallelic inactivation of TP53. The second case harbored a duplication of REL and acquired a translocation affecting IGL and a biallelic inactivation of TP53 during progression. Complicons affecting Igh/Myc have been reported previously in lymphomas of mouse models simultaneously deficient in Tp53 and in genes of the nonhomologous end-joining DNA repair pathway. To the best of our knowledge, this is the first time that IGH/MYC complicons have been reported in human lymphomas. Our findings imply that the two mechanisms resulting in MYC deregulation, that is, translocation and amplification, can occur simultaneously

Recent Changes in Breast Cancer Incidence in Spain, 1980–2004

BACKGROUND: Since the 1980s, Spain experienced two decades of sharply increasing breast cancer incidence. Declines in breast cancer incidence have recently been reported in many developed countries. We examined whether a similar downturn might have taken place in Spain in recent years. METHODS: Cases of invasive female breast cancer were drawn from all population-based Spanish cancer registries that had at least 10 years of uninterrupted registration over the period 1980-2004. Overall and age-specific changes in incidence rates were evaluated using change-point Poisson models, which allow for accurate detection and estimation of trend changes. All statistical tests were two-sided. RESULTS: A total of 80,453 incident cases of invasive breast cancer were identified. Overall age- and registry-adjusted incidence rates rose by 2.9% (95% confidence interval [CI] = 2.7% to 3.1%) annually during the 1980s and 1990s; there was a statistically significant change in this trend in 2001 (95% CI = 1998 to 2004; P value for the existence of a change point <.001), after which incidence declined annually by 3.0% (95% CI = 1.8% to 4.1%). This trend differed by age group: There was a steady increase in incidence for women younger than 45 years, an abrupt downturn in 2001 for women aged 45-64 years, and a gradual leveling off in 1995 for women aged 65 years or older. Separate analyses for registries that had at least 15 years of uninterrupted registration detected a statistically significant interruption of the previous upward trend in breast cancer incidence in provinces that had aggressive breast cancer screening programs and high screening participation rates, including Navarra (change point = 1991, P < .001), Granada (change point = 2002, P = .003), Bizkaia (change point = 1998, P < .001), Gipuzkoa (change point = 1998, P = .001), and Araba (change point = 1997, P = .002). CONCLUSIONS: The recent downturn in breast cancer incidence among Spanish women older than 45 years is best explained by a period effect linked to screening saturation.Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) (AC07-005 to M.P., PM07-004 to R.P-B.) and Carlos III Institute of Health (ISCIII-CIBERESP collaborative agreement “Acción Transversal del Cancer”).S