| 11. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 12. |
- Rantala, Johanna
(författare)
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Genetic predisposition for cancer : genes and genetic counseling
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer accounts for one third of all female cancer cases worldwide. A hereditary component accounts for 10-15% of all breast and ovarian cancer cases. The overall aim of this thesis is to evaluate and improve genetic diagnostic and genetic counseling in hereditary cancer patients. A total of 215 counselees were enrolled to a questionnaire study which aimed to conceptualize risk perception and worry for cancer before and one week after initial oncogenetic counseling and one year after completed genetic investigations. The most incorrect risk perceptions were identified among unaffected counselees with low or the same risk than the general population. The unaffected counselees showed more accurate risk perceptions and decreasing worry for cancer after oncogenetic counseling. The affected counselees overestimated the risk of cancer for children and did not show any change in cancer worry. The relevance of preventive programs was well understood among counselees. (Paper I) Germ-line mutations in BRCA1 and BRCA2 genes predispose to high risk for breast- and ovarian cancer. Penetrance of cancer among BRCA1/2 mutation carriers is incomplete suggesting that genetic- and environmental factors play a role as risk modifier. A large-scale genome-wide association study was performed to identify genetic modifiers of risk for developing breast and ovarian cancer in BRCA1 mutation carriers. The results revealed five SNPs on 19p13 associated with breast cancer risk. Two of these SNPs showed independent associations (rs8170, HR 1.26, 95% CI 1.17-1.35 and rs2363956 HR 0.84, 95% CI 0.80-0.89). The two SNPs showed similar association with estrogen receptor-negative tumors and with triple-negative tumors (Paper II) A randomized questionnaire study was conducted as described above (Paper I). The aim was to evaluate the oncogenetic counseling process and to compare the impact of the initial part of the oncogenetic counseling, when conducted via telephone versus in-person. The results indicate that telephone pre-counseling works as well as in-person pre-counseling. The counselees showed high satisfaction rates with the oncogenetic counseling process. A considerable number of counselees experienced difficulties with the process of creating a pedigree and dissatisfaction with information on surveillance and prevention. The counselees were unsatisfied with the received emotional support during genetic counseling and information on recommended cancer prevention and surveillance. (Paper III) To identify additional breast cancer predisposing genes, a genome-wide linkage study on fourteen large non-BRCA1/2 hereditary breast cancer families was performed. The linkage analyses identified five candidate loci with a HLOD above one. Regions indicating evidence of linkage are located on 6p21, 8q13, 11p12, 18q21 and 22q11. (Paper IV)
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| 13. |
- Rantala, Pekka, et al.
(författare)
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Anthropogenic and biogenic influence on VOC fluxes at an urban background site in Helsinki, Finland
- 2016
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 16:12, s. 7981-8007
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Tidskriftsartikel (refereegranskat)abstract
- We measured volatile organic compounds (VOCs), carbon dioxide (CO2) and carbon monoxide (CO) at an urban background site near the city centre of Helsinki, Finland, northern Europe. The VOC and CO2 measurements were obtained between January 2013 and September 2014 whereas for CO a shorter measurement campaign in April–May 2014 was conducted. Both anthropogenic and biogenic sources were identified for VOCs in the study. Strong correlations between VOC fluxes and CO fluxes and traffic rates indicated anthropogenic source of many VOCs. The VOC with the highest emission rate to the atmosphere was methanol, which originated mostly from traffic and other anthropogenic sources. The traffic was also a major source for aromatic compounds in all seasons whereas isoprene was mostly emitted from biogenic sources during summer. Some amount of traffic-related isoprene emissions were detected during other seasons but this might have also been an instrumental contamination from cycloalkane products. Generally, the observed VOC fluxes were found to be small in comparison with previous urban VOC flux studies. However, the differences were probably caused by lower anthropogenic activities as the CO2 fluxes were also relatively small at the site.
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| 14. |
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| 15. |
- Schrijver, Lieske H, et al.
(författare)
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Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers : an international cohort study
- 2021
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 225:1, s. 1-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive preparations (OCPs) use. While the effects of OCPs in the general population are well established (∼50% reduction), the estimated risk reduction in mutation carriers is much less precise due to potential bias and small sample sizes. In addition, only a few studies have examined the associations between duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer.OBJECTIVE(S): To investigate in more detail the associations between various characteristics of OCP use and risk of ovarian cancer, to provide health care providers and carriers with better risk estimates.STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using OCP data on 3,989 BRCA1 and 2,445 BRCA2 mutation carriers. Age-dependent weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as covariate. To minimize survival bias, analyses were left-truncated at 5 years before baseline questionnaire. Separate analysis were conducted for each of the aspects of OCP use and in a multivariate analysis including all these aspects. In addition, the analysis of duration of OCP use was stratified by recency of use.RESULTS: OCPs were less often used by mutation carriers who were diagnosed with ovarian cancer (Ever use: BRCA1 58.6%, BRCA2 53.5%) than by unaffected carriers (Ever use: BRCA1 88.9%, BRCA2 80.7%. The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer, and 9 and 8 years for ovarian cancer unaffected BRCA1 and BRCA2 carriers, respectively. For BRCA1 mutation carriers univariate analyses showed that both a longer duration of OCP use and more recent use of OCPs were inversely associated with risk of ovarian cancer. However, in multivariate analyses including duration of use, age at first use and time since last use, duration of use proved to be the prominent protective factor (compared with <5 years, 5-9 years HR=0.67;95%CI 0.40-1.12, 10+ years HR=0.37;95%CI 0.19-0.73; ptrend=0.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (Duration of ≥10 years; BRCA1: <15 years since last use: HR=0.24 95%CI 0.14-0.43, 15+ years since last use: HR 0.56 95%CI 0.18-0.59). Univariate results for BRCA2 mutation carriers were similar, but due to limit sample size inconclusive.CONCLUSION: For BRCA1 mutation carriers, a longer duration of OCP use is associated with a greater reduction of ovarian cancer risk and the protection is long term.
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| 16. |
- Sundström, Johanna, et al.
(författare)
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Att borga för likvärdighet? : Kommunala tjänstemäns iscensättande av en ny läroplan för förskolan
- 2021
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Ingår i: Ämnet som blev. - Umeå : Umeå universitet. - 9789178556045 - 9789178556038 ; , s. 111-124
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Konferensbidrag (refereegranskat)abstract
- Detta kapitel handlar om hur, med vilket innehåll och med vilka resurser en ny läroplan för förskolan iscensätts av kommunala tjänstemän i arbetet med rektorerna i en svensk kommun. Studien genomförs som en fallstudie med intervjuer och observationer. Genom ett policy enactmentperspektiv i enlighet med Braun, Ball, Maguire och Hoskins analyseras olika kontextuella dimensioner i studien: situerad, extern, professionell och materiell kontext. Resultatet visar värdet av att kunna använda en redan inarbetad organisation med regelbundna träffar med samtliga kommunala rektorer för förskolan. Förändringar i förskolans nya läroplan tas emot positivt av de kommunala tjänstemännen, och Skolverket framstår som den externa kontext som de visar stor tilltro till. Tjänstemännens egen professionserfarenhet från iscensättande av tidigare läroplaner ligger till grund för att de nu vill borga för likvärdighet mellan förskolor genom att ge samma information och material till samtliga rektorer. I detta arbete utgår de från arbetssätt och en del material som tillhandahålls av Skolverket. Det läroplansinnehåll som framför allt framställs som grundläggande och särskilt utmanande i studien är undervisning och förskollärares utökade pedagogiska ansvar. Genom ingående och praxisnära studier över tid bidrar detta kapitel till forskningsfältet i pedagogiskt arbete med kunskap om huvudmannanivån i förskolan.
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| 17. |
- Tuominen, Jouni, et al.
(författare)
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Constellations of Correspondence : A Linked Data Service and Portal for Studying Large and Small Networks of Epistolary Exchange in the Grand Duchy of Finland
- 2022
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Ingår i: Proceedings of the 6th Digital Humanities in the Nordic and Baltic Countries Conference (DHNB 2022). ; , s. 415-423
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Konferensbidrag (refereegranskat)abstract
- This paper presents the vision of aggregating, harmonizing, and publishing letter catalog metadata (information e.g. of senders, receivers and datings of letters) from cultural heritage (CH) institutions in Finland as a single reconciled Linked Open Data (LOD) service and a semantic portal providing data analytical tools for researchers. The research is conducted as part of the consortium research project Constellations of Correspondence (CoCo). The target of the project is to study – for the first time – scattered, heterogeneous epistolary metadata regarding the period of the Grand Duchy of Finland (1809–1917) as one, integrated dataset and make it interoperable and available. This will enable scholars to ask ambitious research questions in the field of computer science and to conduct empirical, bottom-up case studies e.g. on epistolary culture, communicative networks, and heritagization processes. This paper discusses one of the first datasets acquired by the project, the letter collection of the Board of the Finnish Art Society (1846–1901), provided by the Finnish National Gallery, which contains details of c. 1150 letters sent or received by c. 400 actors.
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| 18. |
- Uusimaa, Johanna, et al.
(författare)
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Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children
- 2007
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 62:3, s. 278-287
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We studied the prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children in a defined population in Northern Ostrobothnia, Finland.METHODS: Children with diagnoses commonly associated with mitochondrial diseases were ascertained. Blood DNA from 522 selected children was analyzed for 3243A>G. Children with the mutation were clinically examined. Information on health history before the age of 18 years was collected from previously identified adult patients with 3243A>G. Mutation segregation analysis in buccal epithelial cells was performed in mothers with 3243A>G and their children whose samples were analyzed anonymously.RESULTS: Eighteen children were found to harbor 3243A>G in a population of 97,609. A minimum estimate for the prevalence of 3243A>G was 18.4 in 100,000 (95% confidence interval, 10.9-29.1/100,000). Information on health in childhood was obtained from 37 adult patients with 3243A>G. The first clinical manifestations appearing in childhood were sensorineural hearing impairment, short stature or delayed maturation, migraine, learning difficulties, and exercise intolerance. Mutation analysis from 13 mothers with 3243A>G and their 41 children gave a segregation rate of 0.80. The mothers with heteroplasmy greater than 50% tended to have offspring with lower or equal heteroplasmy, whereas the opposite was true for mothers with heteroplasmy less than or equal to 50% (p = 0.0016).INTERPRETATION: The prevalence of 3243A>G is relatively high in the pediatric population, but the morbidity in children is relatively low. The random genetic drift model may be inappropriate for the transmission of the 3243A>G mutation.
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