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- Bootpetch, TC, et al.
(author)
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Multi-omic studies on missense PLG variants in families with otitis media
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 15035-
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Journal article (peer-reviewed)abstract
- Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.
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- Candido-dos-Reis, Francisco J, et al.
(author)
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Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer
- 2015
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In: Clinical Cancer Research. - 1078-0432. ; 21:3, s. 7-652
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Journal article (peer-reviewed)abstract
- PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
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- Hollestelle, Antoinette, et al.
(author)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Journal article (peer-reviewed)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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- Milana (ed.), Marcella, et al.
(author)
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BABAR: Becoming Adult Educators in the Baltic-Sea Region
- 2010
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Reports (other academic/artistic)abstract
- This report presents the results from a comparative study of the qualification of adult educators in the Nordic-Baltic region. The study involved Denmark, Estonia and Sweden. The rationale behind the study is a growing interest in adult education resulting from a focus on lifelong learning in the public and political agendas, internationally and nationally. According to the authors of the report, an increased interest in adult education generates an increased interest in the professionalisation of the adult education sector, and thereby in the qualification of those teaching adults: adult educators.Based on this belief, the study and hence the report looks into the role that the qualification of adult educators plays in policy, learning opportunities for those interested in qualifying as adult educators as well as adult educators’ status as professionals. Besides the formation of personal teaching, which is grounded in learning theory, theoretical principles and experiences from practice, the development of a professional identity plays a role in adult educators becoming professionals. Similarly, so does the recognition of adult educators as professionals by society at large.Methodologically, the study is based on document analysis. The documents selected for analysis have been: national and international research reports and articles; official descriptions of national education systems; and policy papers, laws and other legal documents dealing with adult education and/or the qualification of adult educators.The study shows that in all three countries, there has been an increase in the political interest in adult education and training. In 1993, an act on adult education and training was accepted in Estonia and updated in 2001 (Estonian Ministry of Education and Research, 1993). Four years later, in 1997, a huge reform of the adult education and training system was carried out in Sweden, and in 2000, a reform of adult and continuing education was launched in Denmark. The main drivers for the increased focus on adult education and training in all three countries seem to be the needs of the labour market, in light of globalisation and international competition as well as the Lisbon strategy. The study also shows that in spite of the increased focus on adult education and training and its importance, through out policy papers, there seems to be a lack of interest in the quality of the provision, in terms of education and learning processes, including the qualification of adult educators in Denmark and Sweden. In Estonia, a professional qualification standard for adult educators was accepted in 2004. Except for Estonia, thus, the question of qualification of adult educators is practically absent in ongoing national, political debates with respect to adult education and training.In relation to the options for those interested in qualifying as adult educators, it is difficult to find courses or education programmes offering initial education and training. Instead, most courses and education programmes either offer in-service or a combination of initial and in-service education and training. Thus, there are few opportunities for adult educators to acquire the professional knowledge and identity as adult educators, before entering the field. In addition, adult educators, to a high degree, develop their competencies as adult educators through their work.Further, qualification requirements for teaching within adult education and training vary a lot, and are linked to the specific field of adult education. Within general adult education, in all three countries, the requirements are similar to those for teachers in primary and secondary schools with no demands on specific competences in teaching adults. Within vocationally oriented adult education and training, the situation is very similar to that within general adult education, as demands for pedagogical qualifications do not include specific competences in teaching adults. Liberal adult education in all three countries stands out as the least regulated sector in relation to required pedagogical qualifications for educators. Requirements within this sector are set by each employer. Being that an individual’s professional development is tantamount to a society’s recognition of his/her occupation as a professional one, it can be discussed whether adult educators today are considered as being part of a real profession in the three countries.Based on the study, it can be concluded, that:Adult educators are absent within the policy discourse of adult education and training.Adult educators stand on the edge of a profession.Adult educators are self-taught professionals.These issues are worth further attention within both policy and research circles.
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