Search PubMed⌕ Search

Biomedical subjects

Angel Carracedo

Publications and source records attributed to Angel Carracedo.

At least 19 recordsLinked to original sources
PubMed2026

Early and late CTCAE and patient-reported outcomes following lung cancer radiotherapy: A sex-stratified descriptive analysis from the REQUITE cohort.

BACKGROUND: Long-term prospective data on lung cancer patients treated with radiotherapy are limited, restricting understanding of outcomes and sex-specific characteristics. The multicentre REQUITE study provides standardized follow-up data from an international cohort. METHODS: We analysed longitudinal data from 530 lung cancer patients treated with radical radiotherapy (sequential or concurrent chemoradiotherapy, or stereotactic body radiation therapy [SBRT]) between 2014 and 2017 at 16 centres in Europe and the USA. Healthcare professionals prospectively recorded 21 pulmonary, oesophageal, neurological, cardiac, and skin adverse events using CTCAE v4.0. Patient-reported outcomes assessed symptoms, quality-of-life, fatigue, and physical activity. Adverse event incidence was stratified by sex, radiotherapy technique, chemotherapy administration, smoking status, and other clinical factors. RESULTS: At 12 months, 309 patients were evaluable, with 151 having follow-up beyond one year. Pulmonary adverse events were most frequent (40% grade ≥ 2), mainly dyspnoea and cough. Women had higher rates of oesophagitis, and more frequently reported dysphagia, and chest wall pain, while men experienced a higher frequency of cardiac adverse events. Exploratory subgroup analyses identified significant sex-related differences in grade ≥ 3 pulmonary adverse events following SBRT and in overall grade ≥ 2 oesophageal adverse events among patients with clinical stage I-II and those aged >70 years. Patient-reported outcomes showed persistent fatigue and reduced physical activity, particularly in females. Symptom prevalence and severity varied by sex, age, treatment modality, smoking status, and clinical stage. CONCLUSION: The REQUITE-Lung cohort provides prospectively collected real-world data on radiotherapy-related adverse events in lung cancer patients. This study describes patterns of adverse events and patient-reported outcomes according to sex, age, and treatment characteristics. These findings are hypothesis-generating and may support future validation in independent and pooled datasets.

Patient-reported outcomes↗
PubMed2007

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare inherited condition that includes characteristic eyelid malformations and sometimes reduced fertility in females. Genetic studies have implicated mutations in the forkhead transcription factor FOXL2 as responsible for BPES. We report a female and her father with BPES type I, who presented the 1092-1108dup17 mutation in the FOXL2 gene. Molecular studies and the typical clinical features of BPES should allow the dermatologist to reach an early diagnosis and permit the treatment of eyelid alterations and the investigation of infertility.

Adult↗
PubMed2006

Extensive linkage disequilibrium mapping at HTR2A and DRD3 for schizophrenia susceptibility genes in the Galician population.

The serotonin and dopamine neurotransmitter systems are candidate pathways in the development of schizophrenia because of the assumed causal relationship with the observed symptoms as well as effective targeting of the corresponding receptors by antipsychotic drugs. However, genetic association studies have systematically focused on a limited set of genes and single nucleotide polymorphisms (SNPs), including T102C at HTR2A and Ser9Gly at DRD3. Meta-analyses of the associations between these two markers and schizophrenia revealed a true increase in risk, the magnitude of the effect being very low. In the present study we analyzed 260 schizophrenic patients and 354 control subjects from a homogeneous population, the Galician population, using an extensive linkage disequilibrium (LD) mapping approach, genotyping a total of 47 SNPs to test for the existence of additional variants that confer higher risk. We detected nominal significant association with schizophrenia for several haplotype tag SNPs (htSNPs) at HTR2A, although the significance was lost after multiple test corrections. In addition, haplotype analyses involving a sliding window approach, with window size 2 to 4 SNPs, revealed significant differences in frequencies of the DRD3 haplotypes at the 3' half of the gene region. This difference, which remains clearly significant after multiple test corrections (p=0.002, 0.0001, and 0.0025, for window sizes 2, 3, and 4, respectively), was mainly due to over-representation of several rare haplotypes in patients, at the expense of a single common haplotype; this represents interesting evidence of rare haplotypes for susceptibility detected using common htSNPs due to their strong effect.

3' Flanking Region↗
PubMed2006

Testing for genetic structure in different urban Argentinian populations.

Fifteen autosomal short tandem repeat (STR) markers (D3S1358, HUMTH01, D21S11, D18S51, PENTA E, D5S818, D13S317, D7S820, D16S539, CSF1PO, PENTA D, HUMvWA, D8S1179, HUMTPOX, FGA) were analyzed in 1734 individuals living in urban areas of cities from six different Argentinian provinces (Buenos Aires, Neuquén, Tucumán, La Pampa, San Luis, Santa Cruz) in order to determine if a common urban database could be used in Argentina for forensic purposes. Frequencies estimates, Hardy-Weinberg equilibrium (HWE), and other parameters of forensic interest were computed. Comparisons between the six populations, and with published data from one Native American population from Argentina and other urban populations from Argentina and Europe were also performed. Our results reveal evidences for population structure, both when testing for genetic differentiation and when comparing frequencies distributions between different pairs of populations. Therefore, caution should be taken when using a common pooled database with general forensic purposes in Argentina.

Argentina↗
PubMed2006

Microsatellite autosomal genotyping data in four indigenous populations from El Salvador.

Fifteen microsatellite loci (D3S1358, TH01, D21S11, D18S51, PENTA E, D5S818, D13S317, D7S820, D16S539, CSF1PO, PENTA D, vWA, D8S1179, TPOX, and FGA) have been genotyped in four indigenous populations from El Salvador (Central America), namely, Conchagua, Izalco, Panchimalco, and San Alejo. Here we have obtained values for several indices of forensic interest for these population samples. Population differentiation test showed no significant statistical differences between these four populations, and an AMOVA test indicates that most of the genetic variation (approximately 100%) occurs within individuals. Population pairwise genetic comparisons with other population samples seem to indicate the existence of a major Native American component in the populations from El Salvador.

DNA Fingerprinting↗
PubMed2006

Distinct phenotypic features and gender-specific disease manifestations in a Spanish family with desmin L370P mutation.

Desminopathies represent a subtype of myofibrillar myopathy caused by mutations in the DES gene, which cause myofibril disruption and intracellular inclusions containing desmin and other protein components. Desminopathy mainly involves skeletal and cardiac muscle, separately or together. Both autosomal dominant and autosomal recessive inheritance have been reported. Here, we describe the second family identified to date with an L370P desmin mutation. The disease in this family shows autosomal dominant inheritance with a particular phenotype, where males suffer from sudden death of cardiac origin while females exhibit a more benign myopathy of distal onset and slower progression. Because the only family previously identified with this mutation was limited to one studied patient, the present kindred represents the largest clinical investigation of the phenotype associated with the L370P mutation.

Adult↗
PubMed2006

Genomic rearrangements at the BRCA1 locus in Spanish families with breast/ovarian cancer.

BACKGROUND: Large genomic rearrangements (LGRs) account for a substantial proportion of the BRCA1 disease-causing changes, or variations, identified in families with hereditary breast/ovarian cancer [HB(O)C]. Great differences in the spectrum and prevalence of BRCA1 LGR have been observed among populations. Here we report the first comprehensive analysis of BRCA1 LGRs conducted in Spain. METHODS: We used multiplex ligation-dependent probe amplification (MLPA) to screen for BRCA1 LGRs in the index case individuals of 384 HB(O)C families who previously tested negative for BRCA1 and BRCA2 point variations, small insertions, and deletions. An alternative set of MLPA probes, long-range PCR, and real-time PCR were used to confirm positive results. RESULTS: We have identified 8 different BRCA1 rearrangements (del exon 1-24, del exon 8-13, del exon 11-15, del exon 14, dup exon 19-20, dup exon 20, exon 21-22 amplification, and del exon 23-24). With the exception of del exon 8-13, they are novel alterations. Overall, BRCA1 LGRs explain 1.4% of the Spanish HB(O)C families, and they account for 8.2% of all BRCA1 pathogenic variations identified in our study population. BRCA1 genetic variants affecting hybridization of commercially available MLPA probes are very rare in our population. CONCLUSIONS: Screening for BRCA1 LGRs should be mandatory in Spanish HB(O)C families. A high proportion of country-specific rearrangements are scattered along the gene. MLPA is a robust method to screen for LGRs in our population. MLPA analysis of positive samples with an alternative set of probes, together with long-range PCR and real-time PCR, is a feasible approach to confirm results in cases in which LGR breakpoints have not been characterized.

BRCA1 Protein↗
PubMed2006

A multiplex assay with 52 single nucleotide polymorphisms for human identification.

A total of 52 SNPs reported to be polymorphic in European, Asian and African populations were selected. Of these, 42 were from the distal regions of each autosome (except chromosome 19). Nearly all selected SNPs were located at least 100 kb distant from known genes and commonly used STRs. We established a highly sensitive and reproducible SNP-typing method with amplification of all 52 DNA fragments in one PCR reaction followed by detection of the SNPs with two single base extension reactions analysed using CE. The amplicons ranged from 59 to 115 bp in length. Complete SNP profiles were obtained from 500 pg DNA. The 52 loci were efficiently amplified from degraded samples where previously only partial STR profiles had been obtained. A total of 700 individuals from Denmark, Greenland, Somalia, Turkey, China, Germany, Taiwan, Thailand and Japan were typed, and the allele frequencies estimated. All 52 SNPs were polymorphic in the three major population groups. The mean match probability was at least 5.0 x 10(-19) in the populations studied. Typical paternity indices ranged from 336 000 in Asians to 549 000 in Europeans. Details of the 52 SNP loci and population data generated in this work are freely available at http://www.snpforid.org.

DNA Fingerprinting↗
PubMed2006

Dissection of mitochondrial superhaplogroup H using coding region SNPs.

Haplogroup H (hg H) includes about 40-50% of the West Eurasian mitochondrial DNA (mtDNA) samples investigated so far. In order to enhance discrimination within this haplogroup we selected 45 coding region SNPs that allow to ascribe samples to the main phylogenetic branches of super hg HV (that embraces hg H) and, in particular, to H sublineages with a much finer resolution than previous studies. SNP selection was carried out using the most up-to-date available literature on population and forensic genetics and extended by means of phylogenetic analysis of complete or coding region genomes (<430) and control region sequences. A meticulous inspection of the H phylogeny led us to the observation of various but uncharacterized subclades of hg H. The selected SNPs were amplified in two PCR-multiplex reactions and subsequently targeted in three single-base extension multiplex reactions. A total of 2214 West Eurasian samples were screened for hg H specific loci 2706 and 7028, of which 859 fell in hg H and were further subjected to subhaplogroup typing. We observed 35 different subhaplogroups in total, 33 of which were found at frequencies below 5%. This assay can be used as a prescreening tool in forensic casework for rapid discrimination between divergent lineages (very effective for high-volume crime cases) or as discriminatory assay, when identical hg H haplotypes were obtained by control region sequencing.

Adolescent↗
PubMed2006

Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of Infancy (HI).

Hyperinsulinism of Infancy (HI) is a clinical disorder characterized by deregulation of insulin secretion that leads to profound hypoglycemia. Mutations in genes encoding the ATP-regulated potassium channels of the pancreatic beta-cell, namely ABCC8 (SUR1) and KCNJ11 (Kir6.2), are the major genetic known cause of the disease. To elucidate the genetic etiology of HI in the uncharacterized Spanish population, we conducted extensive sequencing analysis of the ABCC8 (83.5Kb) and KCNJ11 (1.7Kb) genes in 34 Spanish HI patients. Mutations in ABCC8 were detected for both alleles in 13 patients, while ten patients carried only one mutation in one of the ABCC8 alleles. We have detected 22 novel and seven previously described mutations in ABCC8, approximately 60% of them lead to a premature termination signal, which would result in truncated SUR1 proteins. No mutations were found in the KCNJ11 gene. In addition, we report for the first time a 3914bp macrodeletion associated with the HI disorder. The potential pathogenicity of several additional variants is discussed. The spatial pattern of three pathological mutations suggests possible geographical founder effects. This work reveals for first time the involvement of KATP channels in the pathogenesis of an important proportion (approximately 68%) of Spanish HI patients. The spectrum of mutations in Spanish HI patients provides an important tool for diagnosis and prognosis of HI patients in the Spanish population, as well as for genetic counseling of HI families.

ATP-Binding Cassette Transporters↗
PubMed2006

Micro-phylogeographic and demographic history of Portuguese male lineages.

The clinal pattern observed for the distribution of Y-chromosome lineages in Europe is not always reflected at a geographically smaller scale. Six hundred and sixty-three male samples from the 18 administrative districts of Portugal were typed for 25 Y-chromosome biallelic and 15 microsatellite markers, in order to assess the degree of substructuring of male lineage distribution. Haplogroup frequency distributions, Analysis of Molecular Variance (AMOVA) and genetic distance analyses at both Y-SNP and Y-STR levels revealed a general genetic homogeneity of Portuguese sub-populations. The traditional division of the country in north, central and south, which is usually considered in studies addressing questions of the genetic variation distribution in Portugal, was not reflected in the Y-haplotype distribution. Instead, just one sub-region (Alentejo) stood out due to the presence of high diversity levels and a higher number of different lineages, at higher frequencies than in other regions. These results are reconciled with the historical evidence available, assuming that from prehistorical times down to the end of the medieval period this region harboured the most diverse groups of people and, because of economic depression, remained relatively isolated from recent homogenisation movements. The finding of a broadly homogeneous background for the Portuguese population has vast repercussions in forensic, epidemiological and association studies.

Chromosomes, Human, Y↗
PubMed2006

SUMO4 and MAP3K7IP2 single nucleotide polymorphisms and susceptibility to rheumatoid arthritis.

OBJECTIVE: To explore the role of single nuclear polymorphisms (SNP) in 2 candidate genes, SUMO4 and MAP3K7IP2, in susceptibility to rheumatoid arthritis (RA). METHODS: Two cohorts from different Spanish towns totalling 635 patients with RA and 826 controls were studied. Six SNP were genotyped by matrix assisted laser desorption-ionization time-of-flight (MALDI-TOF) with the MassARRAY SNP genotyping system. RESULTS: We found no association with susceptibility to RA for any of the SNP including a previously described functional variant in the SUMO4 gene (163A-->G). RA susceptibility was independent of the haplotypes defined by the 6 SNP and there was also no association with clinical features of RA. Conclusion. SUMO4 and MAP3K7IP2 SNP did not significantly influence predisposition to and features of RA, in contrast to previous genetic and functional evidence that suggested their involvement.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Evaluating HapMap SNP data transferability in a large-scale genotyping project involving 175 cancer-associated genes.

One of the many potential uses of the HapMap project is its application to the investigation of complex disease aetiology among a wide range of populations. This study aims to assess the transferability of HapMap SNP data to the Spanish population in the context of cancer research. We have carried out a genotyping study in Spanish subjects involving 175 candidate cancer genes using an indirect gene-based approach and compared results with those for HapMap CEU subjects. Allele frequencies were very consistent between the two samples, with a high positive correlation (R) of 0.91 (P<<1x10(-6)). Linkage disequilibrium patterns and block structures across each gene were also very similar, with disequilibrium coefficient (r (2)) highly correlated (R=0.95, P<<1x10(-6)). We found that of the 21 genes that contained at least one block larger than 60 kb, nine (ATM, ATR, BRCA1, ERCC6, FANCC, RAD17, RAD50, RAD54B and XRCC4) belonged to the GO category "DNA repair". Haplotype frequencies per gene were also highly correlated (mean R=0.93), as was haplotype diversity (R=0.91, P<<1x10(-6)). "Yin yang" haplotypes were observed for 43% of the genes analysed and 18% of those were identical to the ancestral haplotype (identified in Chimpazee). Finally, the portability of tagSNPs identified in the HapMap CEU data using pairwise r (2) thresholds of 0.8 and 0.5 was assessed by applying these to the Spanish and current HapMap data for 66 genes. In general, the HapMap tagSNPs performed very well. Our results show generally high concordance with HapMap data in allele frequencies and haplotype distributions and confirm the applicability of HapMap SNP data to the study of complex diseases among the Spanish population.

Biomarkers, Tumor↗
PubMed2005

A collaborative study of the EDNAP group regarding Y-chromosome binary polymorphism analysis.

A collaborative study was carried out by the European DNA Profiling Group (EDNAP) in order to evaluate the performance of Y-chromosome binary polymorphism analysis in different European laboratories. Four blood samples were sent to the laboratories, to be analysed for 11 Y-chromosome single nucleotide polymorphisms (SNPs): SRY-1532, M40, M35, M213, M9, 92R7, M17, P25, M18, M153 and M167. All the labs were also asked to submit a population study including these markers. All participating laboratories reported the same results, indicating the reproducibility and robustness of Y-chromosome SNP typing. A total of 535 samples from six different European populations were also analysed. In Galicia (NW Spain) and Belgium, the most frequent haplogroup was R1b*(xR1b1,R1b3df). Haplogroup F*(xK) is one of the most frequent in Austria and Denmark, while the lowest frequency appear in Belgium. Haplogroup frequencies found in this collaborative study were compared with previously published European Y-chromosome haplogroup data.

Chromosomes, Human, Y↗
PubMed2005

A critical reassessment of the role of mitochondria in tumorigenesis.

BACKGROUND: Mitochondrial DNA (mtDNA) is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results. METHODS AND FINDINGS: In our analyses, we take a phylogenetic approach and employ thorough database searches, which together have proven successful for detecting erroneous sequences in the fields of human population genetics and forensics. Apart from conceptual problems concerning the interpretation of mtDNA variation in tumorigenesis, in most cases, blocks of seemingly somatic mutations clearly point to contamination or sample mix-up and, therefore, have nothing to do with tumorigenesis. CONCLUSION: The role of mitochondria in tumorigenesis remains unclarified. Our findings of laboratory errors in many contributions would represent only the tip of the iceberg since most published studies do not provide the raw sequence data for inspection, thus hindering a posteriori evaluation of the results. There is no precedent for such a concatenation of errors and misconceptions affecting a whole subfield of medical research.

Artifacts↗
PubMed2005

A practical guide to mitochondrial DNA error prevention in clinical, forensic, and population genetics.

Several suggestions have been made for avoiding errors in mitochondrial DNA (mtDNA) sequencing and documentation. Unfortunately, the current clinical, forensic, and population genetic literature on mtDNA still delivers a large number of studies with flawed sequence data, which, in extreme cases, damage the whole message of a study. The phylogenetic approach has been shown to be useful for pinpointing most of the errors. However, many geneticists, especially in the forensic and medical fields, are not familiar with either effective search strategies or the evolutionary terminology. We here provide a manual that should help prevent errors at any stage by re-examining data fresh from the sequencer in the light of previously published data. A fictitious case study of a European mtDNA data set (albeit composed from the literature) then demonstrates the steps one has to go through in order to assess the quality of sequencing and documentation.

DNA, Mitochondrial↗