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  • 1
    Keywords: CANCER ; Germany ; POPULATION ; RISK ; GENES ; PROTEIN ; PROTEINS ; TRANSDUCTION ; PATIENT ; ACTIVATION ; MECHANISM ; IMPACT ; CARCINOGENESIS ; signal transduction ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; BREAST ; breast cancer ; BREAST-CANCER ; MUTATION ; SIGNAL-TRANSDUCTION ; cancer risk ; ONCOLOGY ; RE ; BRCA2 ; INCREASE ; analysis ; TESTS ; USA ; BINDING DOMAIN ; CANCER-RISK ; EPITHELIAL OVARIAN-CANCER ; KINASE-ANCHORING PROTEINS
    Abstract: Data from several studies have suggested that polymorphisms in A-kinase anchoring proteins (AKAPs), which are key components of signal transduction, contribute to carcinogenesis. To evaluate the impact of AKAP variants on breast cancer risk, we genotyped six nonsynonymous sing le-nucleotide polymorphisms that were predicted to be deleterious and found two (M4631, 1389G〉T and N2792S, 8375A〉G) to be associated with an allele dose-dependent increase in risk of familial breast cancer in a German population. We extended the analysis of AKAP9 M4631, which is in strong linkage disequilibrium with AKAP9 N2792S, to 9523 breast cancer patients and 13770 healthy control subjects from seven independent European and Australian breast cancer studies. All statistical tests were two-sided. The collaborative analysis confirmed the association of M4631 with increased breast cancer risk. Among all breast cancer patients, the combined adjusted odds ratio (OR) of breast cancer for individuals homozygous for the rare allele TT (frequency = 0.19) compared with GG homozygotes was 1.17 (95% confidence interval [CL] = 1.08 to 1.27, P =.0003), and the OR for TT homozygotes plus GT heterozygotes compared with GG homozygotes was 1.10 (95% Cl = 1.04 to 1.17, P=.001). Among the combined subset of 2795 familial breast cancer patients, the respective ORs were 1.27 (95% Cl = 1.12 to 1.45, P =.0003) and 1.16 (95% Cl = 1.06 to 1.27, P =.001)
    Type of Publication: Journal article published
    PubMed ID: 18334708
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  • 2
    Keywords: CANCER ; EXPRESSION ; CELL-PROLIFERATION ; RISK ; METABOLISM ; polymorphism ; POLYMORPHISMS ; breast cancer ; WOMEN ; gene-environment interaction ; DEHYDROGENASE ; SNPs ; ESTROGEN PLUS PROGESTIN ; REPLACEMENT THERAPY ; mammographic density ; 5-ALPHA-REDUCTASE ; hormone therapy ; Postmenopausal breast cancer risk ; Case-control association study ; MCF-7 ; Progesterone metabolism
    Abstract: Menopausal hormone therapy (MHT) is associated with an increased breast cancer risk in postmenopausal women, with combined estrogen-progestagen therapy posing a greater risk than estrogen monotherapy. However, few studies focused on potential effect modification of MHT-associated breast cancer risk by genetic polymorphisms in the progesterone metabolism. We assessed effect modification of MHT use by five coding single nucleotide polymorphisms (SNPs) in the progesterone metabolizing enzymes AKR1C3 (rs7741), AKR1C4 (rs3829125, rs17134592), and SRD5A1 (rs248793, rs3736316) using a two-center population-based case-control study from Germany with 2,502 postmenopausal breast cancer patients and 4,833 matched controls. An empirical-Bayes procedure that tests for interaction using a weighted combination of the prospective and the retrospective case-control estimators as well as standard prospective logistic regression were applied to assess multiplicative statistical interaction between polymorphisms and duration of MHT use with regard to breast cancer risk assuming a log-additive mode of inheritance. No genetic marginal effects were observed. Breast cancer risk associated with duration of combined therapy was significantly modified by SRD5A1_rs3736316, showing a reduced risk elevation in carriers of the minor allele (p (interaction,empirical-Bayes) = 0.006 using the empirical-Bayes method, p (interaction,logistic regression) = 0.013 using logistic regression). The risk associated with duration of use of monotherapy was increased by AKR1C3_rs7741 in minor allele carriers (p (interaction,empirical-Bayes) = 0.083, p (interaction,logistic regression) = 0.029) and decreased in minor allele carriers of two SNPs in AKR1C4 (rs3829125: p (interaction,empirical-Bayes) = 0.07, p (interaction,logistic regression) = 0.021; rs17134592: p (interaction,empirical-Bayes) = 0.101, p (interaction,logistic regression) = 0.038). After Bonferroni correction for multiple testing only SRD5A1_rs3736316 assessed using the empirical-Bayes method remained significant. Postmenopausal breast cancer risk associated with combined therapy may be modified by genetic variation in SRD5A1. Further well-powered studies are, however, required to replicate our finding.
    Type of Publication: Journal article published
    PubMed ID: 21947678
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  • 3
    Abstract: Menopausal hormone therapy (HT) is associated with increased breast cancer risk among postmenopausal women. Nuclear receptors are involved in steroid hormone- and xenobiotic-mediated signal transduction playing a crucial role in regulating gene expression. Therefore, variations within these genes may influence HT-associated breast cancer risk. We investigated 3,149 postmenopausal breast cancer patients and 5,489 controls from 2 German population-based case-control studies. Thirty-three polymorphisms selected on the basis of known or putative functional relevance located in ESR1, ESR2, PGR, PXR and AR were genotyped. Conditional logistic regression was used to assess multiplicative statistical interaction between polymorphisms and duration of estrogen-progestagen therapy and of estrogen monotherapy with regard to breast cancer risk assuming log-additive and codominant modes of inheritance. We observed an increased risk for women carrying short AR_(CAG) alleles of 〈22 repeats associated with combined estrogen-progestagen therapy compared with those with long alleles (〉 or =22 repeats) (p(interaction) = 0.03). Additionally, risk associated with combination therapy use was significantly modified by 2 PXR polymorphisms with reduction of risk effects in carriers of the minor PXR_rs6785049_G and PXR_rs1054191_A alleles (p(interaction) = 0.04 and 0.05, respectively). Variants in both ESR1 and ESR2 modified risk associated with estrogen monotherapy use. Higher risk were observed in homozygotes for the major ESR1_rs910416_T allele (p(interaction) 〈 0.01) and in homozygotes for the minor ESR2_rs1271572_T, major ESR2_rs4986938_G and minor ESR2_rs928554_G alleles (p(interaction) = 0.02, 0.05, 0.02, respectively). Risk effect modification by ESR1_rs910416 and AR_(CAG)n polymorphisms remained significant after correction for multiple testing. We conclude that genetic variants in nuclear receptor genes may modify HT-associated postmenopausal breast cancer risk.
    Type of Publication: Journal article published
    PubMed ID: 19739075
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  • 4
    Keywords: RECEPTOR ; APOPTOSIS ; CANCER ; HISTORY ; RISK ; SAMPLE ; TUMOR-NECROSIS-FACTOR ; FAMILY ; BIOMARKERS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; FREQUENCIES ; BREAST ; breast cancer ; BREAST-CANCER ; HEALTH ; AGE ; WOMEN ; SNP ; cancer risk ; GENOTYPES ; HETEROGENEITY ; FAMILIES ; VARIANT ; SINGLE NUCLEOTIDE POLYMORPHISMS ; ESTROGEN ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; ALLELES ; biomarker ; GENOTYPE ; FAMILY-HISTORY ; USA ; CANCER-RISK ; Sample Size ; CONSORTIUM ; ERCC4 ; RECEPTOR STATUS ; PROGESTERONE-RECEPTOR GENE ; CASP8
    Abstract: Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASPIO rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1610-6)
    Type of Publication: Journal article published
    PubMed ID: 19423537
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  • 5
    Keywords: RECEPTOR ; CANCER ; EXPRESSION ; GROWTH ; SURVIVAL ; tumor ; KINASE ; DIAGNOSIS ; SUPPORT ; DISEASE ; RISK ; DISTINCT ; PROTEIN ; TUMORS ; PROTEIN-KINASE ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; BREAST ; breast cancer ; BREAST-CANCER ; prevention ; DIFFERENCE ; genetics ; COLORECTAL-CANCER ; PROSTATE-CANCER ; cancer risk ; PROGNOSTIC-FACTORS ; PROGNOSTIC FACTORS ; PROGNOSTIC FACTOR ; heredity ; KERATINOCYTE GROWTH-FACTOR ; HETEROGENEITY ; fibroblast ; SNPs ; overall survival ; GRADE ; PROGNOSTIC-FACTOR ; METAANALYSIS ; ESTROGEN ; USA ; CANCER-RISK ; comparison ; GENOME-WIDE ASSOCIATION ; LOW-GRADE ; FGFR2 ; NUCLEOTIDE ; genetic variants
    Abstract: A three-stage genome-wide association study recently identified single nucleotide polymorphisms ( SNPs) in five loci ( fibroblast growth receptor 2 ( FGFR2), trinucleotide repeat containing 9 ( TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte- specific protein 1 ( LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER- positive ( per- allele OR ( 95%CI) = 1.31 (1.27-1.36)) than ER- negative (1.08 (1.03- 1.14)) disease ( P for heterogeneity = 10-(13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER- positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs ( rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER- negative disease, the strongest association being for rs3803662 in TNRC9 ( 1.14 ( 1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis ( per- allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER- positive and ER- negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment
    Type of Publication: Journal article published
    PubMed ID: 18437204
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  • 6
    Abstract: Menopausal hormone therapy (HT) is associated with an increased breast cancer risk among postmenopausal women. In this study, we investigated genetic effect modification of HT associated breast cancer risk in 3,149 postmenopausal breast cancer patients and 5,489 controls from the two German population-based case-control studies MARIE and GENICA. Twenty-eight polymorphisms of 14 candidate genes including two drug and hormone transporter genes (ABCB1/MDR1 and SHBG), four genes involved in cell cycle regulation (BRCA1, P21/CDKN1A, STK15/AURKA and TP53), six cytokine genes (IGFBP3, IL6, TGFB1, TNF, LTA and IGF1), and two cytokine receptor genes (EGFR and ERBB2) were genotyped using validated methods. Conditional logistic regression was used to assess multiplicative statistical interaction between polymorphisms and duration of estrogen-progestagen therapy and estrogen monotherapy use with regard to breast cancer risk assuming log-additive and co-dominant modes of inheritance. Women homozygous for the major ABCB1_rs2214102_G allele were found to be at a significantly increased breast cancer risk associated with combined estrogen-progestagen therapy [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.12-1.23, P (interaction) = 0.022]. Additionally, risk associated with estrogen monotherapy was modified by BRCA1_rs799917. We observed a trend with increasing minor T alleles leading to the highest risk in homozygous carriers of the minor allele [OR (95% CI) = 1.17 (0.98-1.39), 1.06 (0.98-1.14), and 1.02 (0.94-1.11) for homozygous minor, heterozygous, and homozygous major allele carriers, respectively; P (interaction) = 0.032]. Our results suggest that genetic variants in ABCB1 and BRCA1 may modify the effect of HT on postmenopausal breast cancer risk.
    Type of Publication: Journal article published
    PubMed ID: 19672706
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  • 7
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Komplexe Interventionen - Entwicklung durch Austausch; 13. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin; 20120315-20120317; Hamburg; DOC12ebm028 /20120305/
    Publication Date: 2012-03-06
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 8
    ISSN: 1434-6036
    Keywords: PACS. 05.20.-y Classical statistical mechanics - 05.20.Gg Classical ensemble theory - 02.70.Lq Monte Carlo and statistical methods 75.10.Hk Classical spin models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: We introduce a new nonextensive entropic measure that grows like , where N is the size of the system under consideration. This kind of nonextensivity arises in a natural way in some N-body systems endowed with long-range interactions described by interparticle potentials. The power law (weakly nonextensive) behavior exhibited by is intermediate between (1) the linear (extensive) regime characterizing the standard Boltzmann-Gibbs entropy and (2) the exponential law (strongly nonextensive) behavior associated with the Tsallis generalized q-entropies. The functional is parametrized by the real number in such a way that the standard logarithmic entropy is recovered when . We study the mathematical properties of the new entropy, showing that the basic requirements for a well behaved entropy functional are verified, i.e., possesses the usual properties of positivity, equiprobability, concavity and irreversibility and verifies Khinchin axioms except the one related to additivity since is nonextensive. For , the entropy becomes superadditive in the thermodynamic limit. The present formalism is illustrated by a numerical study of the thermodynamic scaling laws of a ferromagnetic Ising model with long-range interactions.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Acta mechanica 29 (1978), S. 239-255 
    ISSN: 1619-6937
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Description / Table of Contents: Zusammenfassung Eine optische Methode wird beschrieben, die es ermöglicht, die örtlich, zeitlich veränderliche Dicke eines Rieselfilmes zu messen. Messungen dieser Art wurden an mehreren Stellen entlang der Strömungsrichtung für Reynoldszahlen von 145 bis 4030 durchgeführt. Die erhaltenen Meßwerte wurden auf folgende statistische Eigenschaften hin untersucht: Frequenzspektrum, Wahrscheinlichkeitsdichte und Wellengeschwindigkeit. Die gewonnenen Resultate wurden, wenn möglich, mit bekannten, jedoch auf andere Weise ermittelten Ergebnissen verglichen. Es zeigte sich, daß für die Länge des untersuchten Rieselfilmes von 134 cm die Filmeigenschaften stark vom Abstand der Meßstelle zum Beginn des Rieselfilmes abhängen. Diese Abhängigkeit wird schwächer nach einer Übergangszone, in der sich die Wellenbewegung zu stabilisieren scheint. Zumindest drei Bereiche von Reynoldszahlen existieren, die sich durch unterschiedliche statistische Eigenschaften des Rieselfilmes auszeichnen. Das wird besonders bei einem Vergleich der Kurven der Wahrscheinlichkeitsdichten deutlich.
    Notes: Summary An optical method for measuring time varying local film thickness is briefly described. Recordings of film thickness were made for Reynolds numbers (equal to 4Q/v) from 145 to 4030 at varying distances along the direction of the flow. These recordings were digitized and analyzed by digital computer for the following statistical parameters: a) frequency spectrum, b) probability density and c) wave velocity. Where possible these results are compared with those obtained by different thickness measurement methods and recorded at different locations relative to the entrance to the flow. For the length of flow used here, 134 cm, surface characteristics are strongly dependent on distance from the entrance. This dependence appears to lessen after a transition zone where the wave motion stabilizes. There are at least three Reynolds number regions within which the surface characteristics are quite distinct, wavy laminar, transitional and turbulent. These differences are shown by changes in probability density curves from one region to another.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Industrial and engineering chemistry 13 (1974), S. 289-291 
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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