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  • 1
    Online Resource
    Online Resource
    Tuesday, 28 August 2012
    Oxford University Press (OUP) ; 2012
    In:  European Heart Journal Vol. 33, No. suppl 1 ( 2012-08-02), p. 655-939
    Details
    In: European Heart Journal, Oxford University Press (OUP), Vol. 33, No. suppl 1 ( 2012-08-02), p. 655-939
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    URL: Article
    DOI: 10.1093/eurheartj/ehs283
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
    detail.hit.zdb_id: 2001908-7
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  • 2
    Online Resource
    Online Resource
    Common variants in breast cancer risk loci predispose to distinct tumor subtypes
    Springer Science and Business Media LLC ; 2022
    In:  Breast Cancer Research Vol. 24, No. 1 ( 2022-01-04)
    Details
    In: Breast Cancer Research, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2022-01-04)
    Abstract: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate  〈  5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p   〈  0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
    Type of Medium: Online Resource
    ISSN: 1465-542X
    URL: Article
    DOI: 10.1186/s13058-021-01484-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041618-0
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  • 3
    Online Resource
    Online Resource
    Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses
    Springer Science and Business Media LLC ; 2020
    In:  Nature Genetics Vol. 52, No. 6 ( 2020-06), p. 572-581
    Details
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 52, No. 6 ( 2020-06), p. 572-581
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    URL: Article
    DOI: 10.1038/s41588-020-0609-2
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-10-05)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-10-05)
    Abstract: Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10 −8 and 4.42 × 10 −8 ). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A . However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-99409-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 5
    Online Resource
    Online Resource
    The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
    Springer Science and Business Media LLC ; 2019
    In:  npj Breast Cancer Vol. 5, No. 1 ( 2019-11-01)
    Details
    In: npj Breast Cancer, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2019-11-01)
    Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1 , BRCA2 , PALB2 , ATM , and CHEK2 are associated with breast cancer risk. FANCM , which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM :p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2 . These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM −/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM :p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P  = 0.034 and OR = 3.79; P  = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM :p.Arg658* and found that also FANCM :p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P  = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM :p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM -associated tumors.
    Type of Medium: Online Resource
    ISSN: 2374-4677
    URL: Article
    DOI: 10.1038/s41523-019-0127-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2843288-5
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  • 6
    Online Resource
    Online Resource
    The Effect of Fiber Waviness on the Residual Stress State and Its Prediction by the Hole Drilling Method in Fiber Metal Laminates: A Global-Local Finite Element Analysis
    MDPI AG ; 2021
    In:  Metals Vol. 11, No. 1 ( 2021-01-15), p. 156-
    Details
    In: Metals, MDPI AG, Vol. 11, No. 1 ( 2021-01-15), p. 156-
    Abstract: In this paper, fiber waviness, as one of the most frequently occurring defects in fiber reinforced composites, is numerically investigated with regard to the formation of residual stresses in fiber metal laminates. Furthermore, the prediction of the residual stress state in the thickness direction by means of the simulated hole drilling method is studied. To this regard, a global-local finite element analysis based on the submodel technique is presented. The submodel technique essentially consists of two governing steps: In the first step, a global model is first utilized to calculate and analyze the residual stress distribution and deformation in the intrinsically joined hybrid structure. Effective cure-dependent thermo–elastic properties predicted by a numerical homogenization procedure were used to simulate the curing-process and analyze the residual stresses state. However, the dimension of the intrinsically manufactured hybrid plate is large compared to the diameter of the drilled hole (2 mm), so that a local model is necessary, which provides only a geometric partial portion of the global model. The local model takes the global stress state into account and is subsequently used to simulate the incremental hole drilling method with a refined mesh discretization. The production-related fiber waviness is modeled by an element-wise orientation approximating a sinus function. In order to validate the global-local modeling approach, a comparison between numerical results and experimental data from literature is presented. The comparison between global residual stress state (global model) and the simulated hole drilling method (local model) is used to assess the applicability and reliability of the hole drilling method in case of fiber waviness. It is found that an in-plane fiber waviness leads to a rather low variance of residual stresses over thickness. In case of an out-of-plane fiber waviness, oscillating residual stress fields occur over the entire thickness along the fiber direction. Moreover, the current limits of the incremental hole drilling method could be pointed out by the presented investigations. It is seen that the simulated results of the incremental hole drilling method are sensitive to waviness, even if the amplitude-wavelength-ratio is small. Without further adjustment of the calibration coefficients the oscillating stress and strain fields lead, in particular fiber waviness in thickness direction, to unreliable predictions. For the experimental application it can be concluded that the specimens have to be carefully examined with regard to fiber waviness.
    Type of Medium: Online Resource
    ISSN: 2075-4701
    URL: Article
    DOI: 10.3390/met11010156
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662252-X
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  • 7
    Online Resource
    Online Resource
    Measurement and Analysis of Residual Stresses and Warpage in Fiber Reinforced Plastic and Hybrid Components
    MDPI AG ; 2021
    In:  Metals Vol. 11, No. 2 ( 2021-02-16), p. 335-
    Details
    In: Metals, MDPI AG, Vol. 11, No. 2 ( 2021-02-16), p. 335-
    Abstract: Glass/carbon fiber reinforced plastic (GFRP/CFRP) and hybrid components have attracted increasing attention in lightweight applications. However, residual stresses induced in the manufacturing process of these components can result in warpage and, eventually, negatively affect the mechanical performance of the composite structures. In the present work, GFRP, CFRP, GFRP/steel and CFRP/steel hybrid components were manufactured through the prepreg-press-technology always employing the same process parameters. The residual stresses of these components were measured through the hole drilling method (HDM), based on an adequate formalism to evaluate the residual stresses for orthotropic materials including the calculation of the calibration coefficients via finite element analysis (FEA). In FEA, the real material lay-up and mechanical properties of the samples were considered. The warpage induced by residual stresses was measured after the samples were removed from the tool. The measured residual stresses and warpage of four different types of samples were compared and results were analyzed in depth. The results obtained can be extended to other hybrid materials and even could be used for designing multi-stable laminates for application in adaptive structures. Moreover, the effects of the drilling process parameters of HDM, e.g., the drilling speed, the drilling increment and the zero-depth setting, on the resulting residual stresses of GFRP were investigated. The reliability of residual stress measurements in GFRP using HDM was validated through mechanical bending tests. The conclusions concerning the choice of optimal drilling parameters for GFRP could be directly applied for other types of samples considered in the present work.
    Type of Medium: Online Resource
    ISSN: 2075-4701
    URL: Article
    DOI: 10.3390/met11020335
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662252-X
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  • 8
    Online Resource
    Online Resource
    Incidence of major adverse cardiac events following non-cardiac surgery
    Oxford University Press (OUP) ; 2021
    In:  European Heart Journal. Acute Cardiovascular Care Vol. 10, No. 5 ( 2021-06-30), p. 550-558
    Details
    In: European Heart Journal. Acute Cardiovascular Care, Oxford University Press (OUP), Vol. 10, No. 5 ( 2021-06-30), p. 550-558
    Abstract: Major adverse cardiac events (MACE) triggered by non-cardiac surgery are prognostically important perioperative complications. However, due to often asymptomatic presentation, the incidence and timing of postoperative MACE are incompletely understood. Methods and results We conducted a prospective observational study implementing a perioperative screening for postoperative MACE [cardiovascular death (CVD), acute heart failure (AHF), haemodynamically relevant arrhythmias, spontaneous myocardial infarction (MI), and perioperative myocardial infarction/injury (PMI)] in patients at increased cardiovascular risk (≥65 years OR ≥45 years with history of cardiovascular disease) undergoing non-cardiac surgery at a tertiary hospital. All patients received serial measurements of cardiac troponin to detect asymptomatic MACE. Among 2265 patients (mean age 73 years, 43.4% women), the incidence of MACE was 15.2% within 30 days, and 20.6% within 365 days. CVD occurred in 1.2% [95% confidence interval (CI) 0.9–1.8] and in 3.7% (95% CI 3.0–4.5), haemodynamically relevant arrhythmias in 1.2% (95% CI 0.9–1.8) and in 2.1% (95% CI 1.6–2.8), AHF in 1.6% (95% CI 1.2–2.2) and in 4.2% (95% CI 3.4–5.1), spontaneous MI in 0.5% (95% CI 0.3–0.9) and in 1.6% (95% CI 1.2–2.2), and PMI in 13.2% (95% CI 11.9–14.7) and in 14.8% (95% CI 13.4–16.4) within 30 days and within 365 days, respectively. The MACE-incidence was increased above presumed baseline rate until Day 135 (95% CI 104–163), indicating a vulnerable period of 3–5 months. Conclusion One out of five high-risk patients undergoing non-cardiac surgery will develop one or more MACE within 365 days. The risk for MACE remains increased for about 5 months after non-cardiac surgery. Trial registration https://www.clinicaltrials.gov. Unique identifier: NCT02573532.
    Type of Medium: Online Resource
    ISSN: 2048-8726 , 2048-8734
    URL: Article
    DOI: 10.1093/ehjacc/zuaa008
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2663340-1
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  • 9
    Online Resource
    Online Resource
    Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis
    Oxford University Press (OUP) ; 2019
    In:  International Journal of Epidemiology Vol. 48, No. 3 ( 2019-06-01), p. 795-806
    Details
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 48, No. 3 ( 2019-06-01), p. 795-806
    Abstract: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10–4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10–4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10–19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10–6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER] -positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
    URL: Article
    DOI: 10.1093/ije/dyy201
    RVK:
    XF 4100
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1494592-7
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  • 10
    Online Resource
    Online Resource
    Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-04-13)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-04-13)
    Abstract: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values  〈  5 × 10 –8 as genome-wide significant, and p-values  〈  1 × 10 –5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values  〈  1 × 10 5 . The strongest evidence was found for rs4674019 (p-value = 2.27 × 10 –7 ), which showed genome-wide significant interaction (p-value = 3.8 × 10 –8 ) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen–progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-10121-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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