Refine
Has Fulltext
- yes (51)
Year of publication
Document Type
- Journal article (51)
Language
- English (51)
Keywords
- consortium (4)
- genetic modifiers (3)
- investigators (3)
- Escherichia coli (2)
- Staphylococcus aureus (2)
- breast cancer (2)
- common variants (2)
- genome-wide association (2)
- global change (2)
- infection (2)
- modifiers (2)
- ovarian cancer (2)
- single-nucleotide polymorphisms (2)
- survival (2)
- susceptibility loci (2)
- 3D-conformal radiotherapy (1)
- ADHD (1)
- AIDS (1)
- ALS treatment (1)
- ARDS (acute respiratory distress syndrome) (1)
- ARIA (1)
- Amyotrophic Lateral Sclerosis (ALS) (1)
- Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) (1)
- BDNF (1)
- BRCA1/2 (1)
- Bembix (1)
- Blood-brain barrier (1)
- Bombus Spp. Hymenoptera (1)
- Breast-tumors (1)
- CADe (1)
- CAR T-cell (1)
- CARAT (1)
- CDC14A (1)
- COVID-19 (1)
- CT angiography (1)
- CT perfusion (1)
- Chrysididae (1)
- DFNB32 (1)
- DNA (1)
- DNA damage (1)
- DNA storage (1)
- DOTATOC (1)
- DRD1 (1)
- EVT (1)
- EuroQol Five Dimension Five Level Scale (EQ-5D-5L) (1)
- F-19 MRI (1)
- GPCR (1)
- Gene-expression (1)
- Genotype–phenotype correlations (1)
- Germany (1)
- Histologic grade (1)
- Images (1)
- In-vivo (1)
- Inflammation (1)
- Iron-oxide (1)
- Iron-uptake (1)
- Langerhans cells (1)
- Lesions (1)
- MASK (1)
- MRI reporter (1)
- MTH1 (1)
- Male breast cancer (1)
- Mexican coffee plantations (1)
- Mice (1)
- NEIL2 (1)
- NIHSS (1)
- Northeastern Costa Rica (1)
- OGG1 (1)
- Ovarian (1)
- PET (1)
- Particles (1)
- Pathology (1)
- Proteins (1)
- RCT (1)
- Rats (1)
- SSTR (1)
- Salmonella-typhimurium (1)
- Scheimpflug (1)
- Soft-tissue infection (1)
- Sugar-transport (1)
- T cells (1)
- TH1579 (1)
- TH588 (1)
- TIC disorders (1)
- Therapy (1)
- Tracking (1)
- TrkB (1)
- Usher syndrome (1)
- ZNF365 (1)
- [18F]FDG-PET-CT (1)
- \(\alpha\)-phase (1)
- \(\beta\)-phase (1)
- abdominal lymph node metastases (1)
- abscisic acid (ABA) (1)
- acquired immunodeficiency-syndrome (1)
- adolescents (1)
- adverse drug reaction (1)
- aggregation (1)
- alleles (1)
- amyotrophic lateral sclerosis (ALS) (1)
- androgen deprivation therapy (1)
- antibiotic resistance (1)
- anticoagulation (1)
- antimicrobials (1)
- anxiety (1)
- artifacts (1)
- artificial intelligence (1)
- assistive devices (1)
- asthma (1)
- atrial fibrillation (1)
- attention-deficit/hyperactivity disorder (1)
- attention-deficit/hyperactivity disorder (ADHD) (1)
- attention‐deficit (1)
- autism (1)
- autosomal recessive hearing loss (1)
- bacterial cellulose dressing (1)
- basal ganglia (1)
- bead models (1)
- behaviour therapy (1)
- binding analysis (1)
- biology (1)
- biopharmaceuticals (1)
- bipolar disorder (1)
- bird species richness (1)
- brain (1)
- brain asymmetry (1)
- brain laterality (1)
- bridging (1)
- bumblebee nest density (1)
- c-Myc (1)
- calcium (1)
- cancer (1)
- cancer genomics (1)
- cardiac morbidity (1)
- cardiac mortality (1)
- caregiver burden (1)
- carrier transport (1)
- cell (1)
- cell death (1)
- cell differentiation (1)
- cell staining (1)
- charge transport (1)
- chemical mimicry (1)
- children (1)
- chip-seq (1)
- cohort study (1)
- coleoptera (1)
- colonoscopy (1)
- combined retinal dystrophy (1)
- common SNPS (1)
- complex diseases (1)
- coprophagous beetles (1)
- corneal confocal microscopy (1)
- cortico-striatal synapse (1)
- cuticular hydrocarbons (1)
- dSPN (1)
- damage (1)
- data mining (1)
- data quality (1)
- data sharing (1)
- decomposition (1)
- decreasing autonomy (1)
- deep learning (1)
- depression (1)
- digital transformation of health and care (1)
- direct pathway (1)
- disturbance extent (1)
- disturbance severity (1)
- diversity–disturbance relationship (1)
- dung beetle coleoptera (1)
- electroencephalography (EEG) (1)
- elements (1)
- exome sequencing (1)
- expression (1)
- expression signature (1)
- eyes (1)
- family (1)
- fibromyalgia syndrome (1)
- field flow fractionation (1)
- flg22 (1)
- fluorescence-detected sedimentation (1)
- forest communities (1)
- foxes vulpes-vulpes (1)
- frameshift (1)
- functional status (1)
- genetic interaction networks (1)
- genetic variants (1)
- genotype-phenotype patterns (1)
- gilles (1)
- glycolipids (1)
- guard cells (1)
- guidelines & recommendations (1)
- habitat destruction (1)
- haplogroups (1)
- haze (1)
- health-related quality of life (1)
- health-related quality of life (HRQoL) (1)
- hearing impairment (1)
- helminths (1)
- hemolytic anemia (1)
- high-throughput screening (1)
- hill numbers (1)
- hormone-related protein (1)
- hydrodynamics (1)
- hyperactivity disorder (1)
- imaging (1)
- immune check inhibitor (1)
- in vivo experiments (1)
- inappropriate medication (1)
- individualised modular treatment programme (1)
- induced phase transition (1)
- infectious diseases (1)
- informal caregiving (1)
- instensively managed farmland (1)
- intensive care medicine (1)
- intermediate disturbance hypothesis (1)
- invasive cysticerocsis (1)
- ion signaling (1)
- land use (1)
- land-use change (1)
- large vessel occlusion (1)
- large‐scale data (1)
- light-gated proteins (1)
- lipids (1)
- low-molecular heparin (1)
- lymph node metastases (1)
- major histocompatibility complex (1)
- mammographic density (1)
- materials design (1)
- metastasis-directed therapy (1)
- minimum reporting standards (1)
- missing heritability (1)
- mobility (1)
- moisture balance (1)
- molecular diagnostics (1)
- molecular imaging (1)
- motor learning (1)
- multicenter study (1)
- multiparametric CT (1)
- multiple diseases (1)
- multiresistance (1)
- nanocellulose (1)
- natural disturbance (1)
- neonates (1)
- network analysis (1)
- neuropsychiatric disorders (1)
- non-sense mediated mRNA decay (1)
- nursing home residents (1)
- oligmometastases (1)
- oligomers (1)
- oligorecurrence (1)
- oncogenesis (1)
- oncolysis (1)
- organic semiconductors (1)
- oxidative stress (1)
- pH (1)
- paediatric cancer (1)
- pain (1)
- pandemia (1)
- parathyroid carcinoma (1)
- pathogenic bacteria (1)
- patient (1)
- pembrolizumab (1)
- pentacene (1)
- persistence (1)
- plant community composition (1)
- pollen tube (1)
- polymorphism (1)
- polyp (1)
- polypharmacy (1)
- population (1)
- postoperative bleeding (1)
- predictive markers (1)
- prescribing omission (1)
- prolonged cytopenia (1)
- prostate cancer (1)
- protein chip (1)
- proteins (1)
- psychological support (1)
- quality of life (QoL) (1)
- radiation therapy (1)
- repeated surgery (1)
- replication stress (1)
- reporter gene (1)
- rhinitis (1)
- riboflavin (1)
- rule discovery (1)
- sarcoidosis (1)
- secondary wound dressing (1)
- selection (1)
- single-electron transistors (1)
- size exclusion chromatography (1)
- small fiber neuropathy (1)
- socioeconomic status (1)
- somatostatin receptor (1)
- spinco ultracentrifuge (1)
- splicing (1)
- stereotactic body radiotherapy (1)
- stroke (1)
- structural MRI (1)
- subphenotypes (1)
- subtypes (1)
- surfactants (1)
- susceptibility (1)
- susceptibility alleles (1)
- symptom-specific treatment (1)
- synaptic plasticity (1)
- telephone-assisted self-help (1)
- thin-film transistors (1)
- thromboembolism (1)
- transcutaneous auricular vagus nerve stimulation (1)
- transcutaneous cervical vagus nerve stimulation (1)
- transcutaneous vagus nerve stimulation (1)
- translational research (1)
- transmission (1)
- tumor subtypes (1)
- ultraviolet-a (1)
- urban-rural gradient (1)
- variants (1)
- velocity (1)
- virotherapy (1)
- wound healing (1)
- α‐diversity (1)
- β‐diversity (1)
- “bulbar-onset” ALS (bALS) (1)
- “limb-onset” ALS (lALS) (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (12)
- Institut für Humangenetik (8)
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie (4)
- Medizinische Klinik und Poliklinik II (4)
- Neurologische Klinik und Poliklinik (4)
- Physikalisches Institut (4)
- Institut für Molekulare Infektionsbiologie (3)
- Medizinische Klinik und Poliklinik I (3)
- Pathologisches Institut (3)
- Rudolf-Virchow-Zentrum (3)
Sonstige beteiligte Institutionen
BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10\(^{-4}\) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p\(_{interaction}\) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
Disturbances alter biodiversity via their specific characteristics, including severity and extent in the landscape, which act at different temporal and spatial scales. Biodiversity response to disturbance also depends on the community characteristics and habitat requirements of species. Untangling the mechanistic interplay of these factors has guided disturbance ecology for decades, generating mixed scientific evidence of biodiversity responses to disturbance. Understanding the impact of natural disturbances on biodiversity is increasingly important due to human‐induced changes in natural disturbance regimes. In many areas, major natural forest disturbances, such as wildfires, windstorms, and insect outbreaks, are becoming more frequent, intense, severe, and widespread due to climate change and land‐use change. Conversely, the suppression of natural disturbances threatens disturbance‐dependent biota. Using a meta‐analytic approach, we analysed a global data set (with most sampling concentrated in temperate and boreal secondary forests) of species assemblages of 26 taxonomic groups, including plants, animals, and fungi collected from forests affected by wildfires, windstorms, and insect outbreaks. The overall effect of natural disturbances on α‐diversity did not differ significantly from zero, but some taxonomic groups responded positively to disturbance, while others tended to respond negatively. Disturbance was beneficial for taxonomic groups preferring conditions associated with open canopies (e.g. hymenopterans and hoverflies), whereas ground‐dwelling groups and/or groups typically associated with shady conditions (e.g. epigeic lichens and mycorrhizal fungi) were more likely to be negatively impacted by disturbance. Across all taxonomic groups, the highest α‐diversity in disturbed forest patches occurred under moderate disturbance severity, i.e. with approximately 55% of trees killed by disturbance. We further extended our meta‐analysis by applying a unified diversity concept based on Hill numbers to estimate α‐diversity changes in different taxonomic groups across a gradient of disturbance severity measured at the stand scale and incorporating other disturbance features. We found that disturbance severity negatively affected diversity for Hill number q = 0 but not for q = 1 and q = 2, indicating that diversity–disturbance relationships are shaped by species relative abundances. Our synthesis of α‐diversity was extended by a synthesis of disturbance‐induced change in species assemblages, and revealed that disturbance changes the β‐diversity of multiple taxonomic groups, including some groups that were not affected at the α‐diversity level (birds and woody plants). Finally, we used mixed rarefaction/extrapolation to estimate biodiversity change as a function of the proportion of forests that were disturbed, i.e. the disturbance extent measured at the landscape scale. The comparison of intact and naturally disturbed forests revealed that both types of forests provide habitat for unique species assemblages, whereas species diversity in the mixture of disturbed and undisturbed forests peaked at intermediate values of disturbance extent in the simulated landscape. Hence, the relationship between α‐diversity and disturbance severity in disturbed forest stands was strikingly similar to the relationship between species richness and disturbance extent in a landscape consisting of both disturbed and undisturbed forest habitats. This result suggests that both moderate disturbance severity and moderate disturbance extent support the highest levels of biodiversity in contemporary forest landscapes.
Objective
The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer.
Materials and methods
A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations.
Results
Metastasis-directed radiotherapy results in high local control (often > 90% within a follow-up of 1–2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels.
Conclusion
ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304\(\pm\)0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of \(\pm\)0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.
Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR–PET/CT for detecting cardiac sarcoidosis in comparison to CMR.
15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity.
SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up.
In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively.
Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series.
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7x10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95% CI: 1.03-1.21, p = 4.8x10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.