Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Abstract Introduction More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10−6 in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement. Conclusions Differences in associations of common BC susceptibility alleles between BRCA1 and BRCA2 carriers and the general population are explained to a large extent by differences in the prevalence of ER-positive and ER-negative tumors. Estimates of the risks associated with these variants based on population-based studies are likely to be applicable to mutation carriers after taking ER status into account, which has implications for risk prediction

Supplementary Material for: Beurteilung und Förderung der arbeitsbezogenen Selbstwirksamkeitserwartung in der Psychotherapie: Ergebnisse einer Sekundäranalyse einer randomisiert-kontrollierten Studie

Hintergrund: Arbeitsbezogene Selbstwirksamkeitserwartungen (aSW) gelten als Prädiktor für eine erfolgreiche Rückkehr an den Arbeitsplatz bei Arbeitnehmenden mit psychischen Störungen. Spezifische Interventionen zur Förde­rung der aSW existieren bislang jedoch nicht. In der vorliegenden Sekundäranalyse wurde untersucht, ob ein neu entwickeltes kognitiv-imaginatives aSW-Modul geeignet erscheint, (1) imaginative Bewältigungserfahrungen zu erzeugen, (2) reale Bewältigungsbestrebungen vorzuberei­ten (Verhaltensrelevanz; VR) und (3) die aSW zu adressieren. Methoden: Das aSW-Modul wurde im Rahmen einer ar­beitsplatzbezogenen Kurzzeitintervention durchgeführt und videographiert (N = 22). Die aSW und Indikatoren für imaginative Bewältigungserfahrungen (IB) sowie für die VR wurden anhand der Videoaufzeichnungen durch unabhängige Beurteiler:innen eingeschätzt. Zusätzlich erfolgten Selbstbeurteilungen der aSW vor Behandlungsbeginn und zum Zeitpunkt des aSW-Moduls. Ergebnisse: Alle IB-Indikatoren (Kooperation, Lebhaftigkeit, emotionale Beteiligung, kognitive Flexibilität) waren eher hoch ausgeprägt. Bezüglich der VR-Indikatoren zeigte sich, dass Erkenntnisgewinne mode­rat, Intentionen für Verhaltensänderungen eher hoch und die Identifikation von erfolgreichen Modellen gering ausgeprägt waren. Die Fremdberichte der aSW korrelierten mit der selbstberichteten aSW vor Behandlungsbeginn (r = 0,47, p = 0,025) und während des aSW-Moduls (r = 0,51, p = 0,014). Schlussfolgerung: Im aSW-Modul wurden (1) imaginative Bewältigungserfahrungen erzeugt, (2) Intentionen für Verhaltensänderungen gefördert und (3) selbstwirk­sam­keits­relevante Kognitionen aktiviert. Es erscheint geeignet zur kognitiv-motivationalen Vorbereitung von Bewältigungsbestrebungen. Forschungsbedarf besteht hinsichtlich der Effekte des Interventionsmoduls auf reale Bewältigungs­erfahrungen und die Entwicklung der aSW

The family of Peps and their precursors in Arabidopsis : differential expression and localization but similar induction of pattern-triggered immune responses

In Arabidopsis thaliana, the endogenous danger peptides, AtPeps, have been associated with plant defences reminiscent of those induced in pattern-triggered immunity. AtPeps are perceived by two homologous receptor kinases, PEPR1 and PEPR2, and are encoded in the C termini of the PROPEP precursors. Here, we report that, contrary to the seemingly redundant AtPeps, the PROPEPs fall at least into two distinct groups. As revealed by promoter-β-glucuronidase studies, expression patterns of PROPEP1-3, -5, and -8 partially overlapped and correlated with those of the PEPR1 and -2 receptors, whereas those of PROPEP4 and -7 did not share any similarities with the former. Moreover, bi-clustering analysis indicated an association of PROPEP1, -2, and -3 with plant defence, whereas PROPEP5 expression was related to patterns of plant reproduction. In addition, at the protein level, PROPEPs appeared to be distinct. PROPEP3::YFP (fused to yellow fluorescent protein) was present in the cytosol, but, in contrast to previous predictions, PROPEP1::YFP and PROPEP6::YFP localized to the tonoplast. Together with the expression patterns, this could point to potentially non-redundant roles among the members of the PROPEP family. By contrast, their derived AtPeps, including the newly reported AtPep8, when applied exogenously, provoked activation of defence-related responses in a similar manner, suggesting a high level of functional redundancy between the AtPeps. Taken together, our findings reveal an apparent antagonism between AtPep redundancy and PROPEP variability, and indicate new roles for PROPEPs besides plant immunity