Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: ACTIVATION, ASSOCIATION, BRCA2, BREAST, breast cancer, BREAST-CANCER, CANCER, cancer risk, CARCINOGE
    Abstract: Overexpression of the proto-oncogene ERBB2 (HER2/NEU) has been observed in 20-30% of breast cancers involving poor prognosis. Genetic alterations within ERBB2 have been shown to induce carcinogenesis and metastasis. We investigated eight annotated single nucleotide polymorphisms for occurrence in familial breast cancer samples. The confirmed variants Ile654Val, Ile655Val and Ala1170Pro were analysed in subsequent epidemiological studies on familial breast cancer risk. While Ala1170Pro resides within a C-terminally located regulatory domain, the two adjacent polymorphisms Ile654Val and Ile655Val are part of the transmembrane domain. A case-control study analysing a cohort of 348 German familial breast cancer cases and 960 corresponding controls showed no significant association of either Ile655Val (OR = 1.05, 95% CI = 0.82-1.34, P = 0.728) or Ala1170Pro (OR = 0.94, 95% CI = 0.74-1.20, P = 0.632) with familial breast cancer risk. Differences in haplotype frequencies between cases and controls could also not be detected. The ERBB2 variant Ile654Val, however, revealed an increased risk for carriers of the heterozygous Val654 allele (OR = 2.56, 95% CI = 1.08-6.08, P = 0.028). The rare Val654 variant is linked with the more frequent Val655, resulting in two consecutive valine instead of two isoleucine residues within the transmembrane domain. Computational analyses suggest that the Val654-Val655 allele provokes receptor dimerization and activation, thus stimulating kinase activity and cell transformation. We hypothesize that ERBB2 Val654 represents an oncogenic variant which might, in addition, influence clinical outcome and predict a worse prognosis
    Type of Publication: Journal article published
    PubMed ID: 15550452
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: 8Q24, AGE, ARRAYS, BURKITTS-LYMPHOMA, CHILDHOOD, CHROMOSOMAL-ABNORMALITIES, C-MYC, DELETION, DIAGNOS
    Abstract: Partial trisomies are chromosome abnormalities resulting in a broad range of malformations depending on the size and location of the chromosomal rearrangement. Whereas diagnosis of these syndromes is usually made in early childhood, few descriptions exist about the clinical picture in adulthood. We report on a patient diagnosed at the age of 43 years with a 47,X-Y,+der(22)t(8;22)(q24.13;q11.21) karyotype and predominant clinical features of trisomy 8q. To our knowledge, this is the oldest patient described with a partial trisomy 8. The patient presented with moderate intellectual disability, a past history of epilepsy and facial anomalies. In addition, a large cell non-Hodgkin lymphoma was diagnosed in adulthood. Detailed breakpoint mapping by single nucleotide polyrnorphism (SNP) arrays showed that the derivative chromosome contains a full-length copy of the C-MYC oncogene. Given that trisomy 8q is the most frequent secondary chromosomal abnormality in hematological diseases, the possibility of a genetic predisposition for these disorders in patients with 8q duplication is raised. (c) 2006 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 16838305
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: ARRAYS, COPY NUMBER, Germany, HUMAN GENOME, IDENTIFICATION, microarray, polymorphism, POLYMORPHISMS
    Type of Publication: Journal article published
    PubMed ID: 16572511
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: RECEPTOR ; CANCER ; EXPRESSION ; AGENTS ; Germany ; THERAPY ; RISK ; GENE ; GENE-EXPRESSION ; GENES ; transcription ; TIME ; PATIENT ; TRANSCRIPTION FACTOR ; IMPACT ; RISK-FACTORS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; ALPHA ; BREAST ; breast cancer ; BREAST-CANCER ; ACID ; hormone ; gene expression ; risk factors ; cancer risk ; HIGH-RISK ; DNA-DAMAGE ; EXCHANGE ; CANCER-PATIENTS ; DIABETES-MELLITUS ; CANCER PATIENTS ; ESTROGEN-RECEPTOR ; TAMOXIFEN ; signaling ; CBP ; REGRESSION ; ASSOCIATIONS ; RE ; VARIANT ; ESTROGEN ; CANCER DEVELOPMENT ; NUCLEAR RECEPTORS ; estrogen receptor ; p300 ; RISK-FACTOR ; CANCER-RISK ; FAMILIAL BREAST ; familial breast cancer ; OVARIAN ; MUTATION ANALYSIS ; genotype combination ; GAMMA COACTIVATOR ; PREINVASIVE MAMMARY-TUMORS ; STEROID-HORMONE RECEPTORS
    Abstract: The mitogen effect of the ovarian steroid estrogen is a strong risk factor for breast cancer development. This effect is mainly mediated by the estrogen receptor alpha, a hormone inducible transcription factor, which activates gene expression through recruiting multiple coactivators, such as PPARGC1A, PPARGC1B and EP300. We tested the hypothesis that non-conservative, putative functional amino acid exchanges in PPARGC1A, PPARGC1B and EP300 act as low-penetrance familial breast cancer risk factors. The analysis of 816 BRCA1/2 mutation-negative familial breast cancer patients and 1012 controls revealed an association of the PPARGC1A Thr612Met polymorphism with familial breast cancer (OR = 1.35, 95% CI 1.00-1.81, P = 0.049), high-risk familial breast cancer (OR = 1.51, 95% CI 1.08-2.12, P = 0.017) and bilateral familial breast cancer (OR = 2.30, 95% CI 1.24-4.28, P = 0.009). Logistic regression analyses of the PPARGC1B Ala203Pro variant showed an increased familial breast cancer risk of heterozygous and homozygous variant allele carriers (OR = 1.48, 95% CI 1.15-1.91, P = 0.002). The genotype-combination analysis of the associated PPARGC1A Thr612Met variant and the associated PPARGC1B Ala203Pro variant suggests an allele dose-dependent breast cancer risk (P-trend = 0.0004). Our results indicate for the first time the importance of inherited variants in the estrogen receptor coactivator genes PPARGC1A and PPARGC1B for familial breast cancer susceptibility. Owing to their impact on estrogen signaling, these polymorphisms might also influence adjuvant anti-estrogen therapy, using agents such as tamoxifen and raloxifen, and outcome of breast cancer patients
    Type of Publication: Journal article published
    PubMed ID: 16704985
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: CANCER ; carcinoma ; Germany ; KINASE ; THERAPY ; RISK ; GENE ; GENES ; IMPACT ; CARCINOGENESIS ; ASSOCIATION ; polymorphism ; SUSCEPTIBILITY ; VARIANTS ; BREAST ; breast cancer ; BREAST-CANCER ; OVARIAN-CANCER ; BLADDER-CANCER ; cancer risk ; COLORECTAL CANCERS ; OVEREXPRESSION ; ONCOLOGY ; case-control study ; RE ; VARIANT ; GENOTYPE ; LOSSES ; CANCERS ; CANCER-RISK ; FAMILIAL BREAST ; familial breast cancer ; AURORA KINASES ; CHROMOSOME SEGREGATION ; HARDY-WEINBERG DISEQUILIBRIUM ; MITOTIC KINASE
    Abstract: Aurora genes play a crucial role in tumourigenesis and are overexpressed in many kinds of cancers. We investigated whether coding variants within the Aurora genes are associated with familial breast cancer risk. While AURKA Phe31Ile (1712T 〉 A) and AURKB Thr298Met (893G 〉 A) showed no association, the synonymous AURKB Ser295Ser (885A 〉 G) polymorphism resulted in an increased breast cancer risk for carriers of the homozygous 885G genotype (OR = 1.45, 95% CI = 1.05-2.0, P = 0.02). Due to the impact of aurora kinases in the loss of chromosomal integrity during carcinogenesis, this variant may also influence the therapy outcome in breast cancer. (c) 2006 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16762494
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: RECEPTOR ; CANCER ; CELLS ; Germany ; human ; KINASE ; RISK ; SITE ; SITES ; PROTEIN ; PROTEINS ; DIFFERENTIATION ; TIME ; PATIENT ; IMPACT ; DOMAIN ; BINDING ; PHOSPHORYLATION ; PROTEIN-KINASE ; ASSOCIATION ; polymorphism ; SUSCEPTIBILITY ; VARIANTS ; ALPHA ; BREAST ; breast cancer ; BREAST-CANCER ; ACID ; TARGET ; resistance ; cancer risk ; GROWTH-INHIBITION ; LOCALIZATION ; PKA ; EXCHANGE ; CANCER-PATIENTS ; specificity ; CANCER PATIENTS ; OVEREXPRESSION ; CYCLIC-AMP ; ESTROGEN-RECEPTOR ; TAMOXIFEN ; SUBCELLULAR-LOCALIZATION ; RE ; VARIANT ; HUMAN CANCER ; ESTROGEN ; INTERVAL ; analysis ; estrogen receptor ; HUMAN CANCERS ; RISK-FACTOR ; CANCERS ; CANCER-RISK ; FAMILIAL BREAST ; familial breast cancer ; PROTEIN-KINASE-A ; breast cancer susceptibility ; ALPHA SUBUNIT ; ANTISENSE OLIGODEOXYNUCLEOTIDE ; D-AKAP2 ; RII-BETA SUBUNIT
    Abstract: Overexpression of cAMP-dependent protein kinase A (PKA) is a hallmark of the great majority of human cancers including breast cancer. A-kinase anchoring proteins (AKAPs) coordinate the specificity of PKA signalling by localizing the kinase to its subcellular sites. We tested the hypothesis whether the functional amino acid exchange Ile646Val, located in the kinase-binding domain of AKAP10, is a low-penetrance familial breast cancer risk factor. Ile646Val alters the binding of AKAP10 to PKA and is associated with morbidity. The analysis of 787 BRCA1/2 mutation-negative familial breast cancer patients and 993 controls revealed an association of the AKAP10 Ile646Val polymorphism with increased familial breast cancer risk [odds ratio (OR) = 1.25, 95% confidence interval (CI) 1.03-1.51, P = 0.024]. Our previous study has shown that AKAP13 Lys526Gln is associated with familial breast cancer (OR = 1.58). Here, we discovered that carriers of both variants, AKAP10 Ile646Val and AKAP13 Lys526Gln, are at a further enhanced breast cancer risk (OR = 2.41, 95% CI 1.30-4.46, P = 0.005). PKA is a major target of therapeutic anticancer strategies. Phosphorylation of the estrogen receptor (ER) alpha by PKA induces resistance against the anti-estrogen tamoxifen. Our results indicate for the first time the importance of AKAP10 Ile646Val for familial breast cancer susceptibility. Due to the impact of Ile646Val on the subcellular localization of PKA, it will be interesting to investigate whether this polymorphism influences the effectiveness of PKA and tamoxifen based therapeutic anticancer concepts
    Type of Publication: Journal article published
    PubMed ID: 16956908
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: Germany ; DEATH ; DISEASE ; liver ; POPULATION ; DISTINCT ; GENE ; GENES ; PATIENT ; FAMILY ; MEMBERS ; polymorphism ; single nucleotide polymorphism ; ACID ; TRANSPORT ; AGE ; LINKAGE ANALYSIS ; MUTATION ; etiology ; DAMAGE ; genotyping ; MUTATIONS ; FAILURE ; fibrosis ; ADULT ; ADULTS ; CHILDHOOD ; SIBLINGS ; FAMILIES ; CANDIDATE GENES ; TRANSPORTER ; BILE ; hepatobiliary transport ; MUTATIONAL ANALYSIS ; analysis ; single-nucleotide polymorphism ; PREGNANCY ; USA ; MDR3 GENE ; CANDIDATE ; LIVER-DISEASE ; URSODEOXYCHOLIC ACID ; FAMILY-MEMBERS ; GENOME-WIDE ; BILIARY-CIRRHOSIS ; CHOLELITHIASIS ; FAMILIAL INTRAHEPATIC CHOLESTASIS ; SCLEROSING CHOLANGITIS
    Abstract: Cholestatic liver disease (CLD) is a major cause of progressive liver damage and liver failure. Several forms of biliary cirrhosis are caused by mutations in specific genes. We sought to identify a genetic defect in a family with CLD impossible to assign to a distinct pathogenic entity. Clinical and histopathological characterization of the family members, microarray-based single-nucleotide polymorphism genotyping, and analysis of candidate genes were performed. Among six of I I siblings severely affected by idiopathic CLD in a family from a population isolate in Transylvania, three died of cirrhosis (aged 5, 7, and 43 years) and three had adult-onset disease with small duct cholangiopathy, including ductopenia. Others were mildly affected and experienced intrahepatic cholestasis of pregnancy, miscarriages, or stillbirth. Pedigree studies revealed distant parental consanguinity. Genome-wide linkage analysis and autozygosity mapping yielded a single maximal lod-score of 3.88 on chromosome 7q21.1-7q22, excluding other genomic loci. Sequencing of ABCB4 at this locus revealed a novel missense mutation c.2362C〉T (p.Arg788Trp) which cosegregated with severity of disease. Bile from a mutation homozygote showed a reduced phosphatidylcholine/bile acid ratio, consistent with reduced ABCB4 phosphatidylcholine transport activity. Conclusion: We show that a missense mutation in ABCB4 is a cause for ductopenic CLD in adulthood. Allelic status correlated with severity of liver disease ranging from intrahepatic cholestasis of pregnancy through fibrosis to cirrhosis and death in childhood and adulthood. Mutational analysis of ABCB4 should be generally considered in all patients with cholestatic liver disease of unknown etiology regardless of age and onset of disease
    Type of Publication: Journal article published
    PubMed ID: 18781607
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: ACTIVATION, AMPLIFICATION, ASSOCIATION, BRCA1, BREAST, breast cancer, BREAST-CANCER, BREAST-TUMORS,
    Abstract: The nuclear receptor coactivator 3 (NCOA3, also known as AIB1) is a coactivator of nuclear receptors like the estrogen receptor. NCOA3 is overexpressed in similar to 60% of primary human breast tumors, and high levels of NCOA3 expression are associated with tamoxifen resistance and worse survival rate. In contrast, NCOA3 deficiency suppresses nu w-Ha-ras - induced breast cancer initiation and progression in mice. Here, we analyzed the influence of NCOA3 coding single nucleotide polymorphisms on breast cancer risk by performing a case-control study using a German and a Polish study population and identified an association between NCOA3 polymorphisms and breast cancer. A joint analysis of the German and the Polish study population revealed a significant protective effect for the 1758G 〉 C (Q586H) and 2880A 〉 G (T960T) variants. In addition, haplotype analysis showed a protective effect of the 1758C-2880A and 1758G-2880G haplotypes (odds ratio 0.79; 95% confidence interval, 0.67-0.93; P = 0.004). Because of the impact of NCOA3 in antiestrogen therapy resistance, these polymorphisms might also influence therapy outcome in breast cancer
    Type of Publication: Journal article published
    PubMed ID: 15788663
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: ARRAY, ARRAYS, DISEASE, EVENTS, FAMILY, FREQUENCY, GENE, GENERATION, GENES, GENOME, GENOTYPE, German
    Abstract: There is a great deal of interest in understanding the non-random distribution of recombination events over the human genome, because it has important implications for using linkage disequilibrium (LD) to identify human disease genes. So far, only a few recombination hotspots in the human genome have been characterised and the identification of new crossover hotspots will contribute to a better understanding of the mechanisms that govern their formation and distribution. This study shows that high-density single nucleotide polymorphism (SNP) arrays, together with the presented analysis method, are an appropriate tool for generating a whole-genome recombination pattern and for detecting new crossover regions with enhanced recombination frequency. Based on the genotype data of 16 members of a Caucasian three-generation family, we identified 825 crossover regions. The average recombination frequency of females and males was 0.77 and 0.56 cM/Mb, respectively. We detected 24 crossover regions showing elevated recombination activity, which comprised known hotspots, like the MHC II region, confirming the non-random distribution of recombination events along the genome. Interestingly, 29.2% of the identified crossover hotspot regions overlapped with regions flanked by segmental duplications published by Bailey et al. (Science 297:1003-1007, 2002) suggesting that segmental duplications and crossover hotspot regions are mechanistically linked. By extrapolating the results of the present study, we conclude that it might be feasible, at least in part, to estimate to what extent the block-like pattern of LD exactly relies on the genome-wide crossover pattern using the next generation high-density SNP microarrays
    Type of Publication: Journal article published
    PubMed ID: 15933847
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: ACID, AGE, AMINO-ACID, APOPTOSIS, BCL-X-L, BRCA1, BRCA2, BREAST, breast cancer, BREAST-CANCER, CANCE
    Abstract: c-MYC is a multifaceted protein that regulates cell proliferation, differentiation and apoptosis. Its crucial role in diverse cancers has been demonstrated in several studies. Here, we analysed the influence of the rare c-MYC Asn11Ser polymorphism on familial breast cancer risk by performing a case-control study with a Polish (cases n = 349; controls n = 441) and a German (cases n = 356; controls n = 655) study population. All cases have been tested negative for mutations in the BRCA1 and BRCA2 genes. A joint analysis of the Polish and the German study population revealed a 54% increased risk for breast cancer associated with the heterozygous Asn11Ser variant (OR = 1.54, 95% CI 1.05-2.26, p = 0.028). The breast cancer risk associated with this genotype increases above the age of 50 years (OR = 2.24, 95% CI 1.20-4.21, p = 0.012). The wild-type amino acid Asn of this polymorphism is located in the N-terminal MYC transactivation domain and is highly conserved not only among most diverse species but also in the N-MYC homologue. Due to the pivotal role of c-MYC in diverse tumours, this variant might affect the genetic susceptibility of other cancers as well. (c) 2005 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 15929079
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...