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- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-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.MethodsAmong 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.ResultsEighty-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.ConclusionThis 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.
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| 2. |
- Ljungblom, Mia, 1965-
(författare)
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Respect for People : Developing alternative understandings and relationships to ethics, leadership, and culture in Lean implementations.
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Successful Lean implementation is a combination of both technology and culture, using bothkey principles of continuous improvement (CI) and respect for people (RFP). However, manyorganizations fail to implement Lean and critical factors in this failure are leadership, cultureand the lack of RFP. When CI and RFP permeate an organization, it is called real Lean, andwhen there is only a focus on CI it is called false Lean. Without Lean culture, where RFP playsthe main role, Lean becomes an add-on tool.The purpose of this thesis is twofold. The first part of the purpose is to developalternative understandings of RFP and relationships to ethics, leadership and culture in Leanimplementations. The second part is to suggest a normative framework helping leaders toachieve real Lean.The purpose is operationalized into the following research questions: - What understandingsof RFP can enable Lean implementations? - What understandings of ethics, leadership andculture can enable Lean implementations? - How can these understandings form a normativeframework for Lean leaders?The study is a qualitative, exploratory and descriptive case study with anabductive approach. The data have been collected by documents, interviews, questionnaires,and participant observations. Content and discourse analysis are used together with pattern-matchingto analyse the data.The study shows that it is important to understand the differences in culture (national/organizational) prior to Lean implementation and to conduct an organizational analysis to findsimilarities and differences between Lean and organizational values. The study also finds thatRFP is composed of elements in different cultural levels. The elements identified are ethics,leadership and culture, each of which has invisible elements, often linked to Japanese religionsand traditions, that need to be visualized and discussed. Previous research has presented variousframeworks and models exist but these are more know-what than know-how. Organizationsneed more know-how to create real Lean where RFP can be seen as the ‘how’.I developed a leadership model called Developmental Lean leadership (DLL) that aims tofind leadership that supports both employee and organizational development and can meet theneeds of a Lean leader, which are to act as a role model and support the development towardsa real Lean culture.I also developed a normative framework for Lean leaders called the RFP house, which it ishoped will help Lean leaders achieve real Lean in their organizations during implementations.
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