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- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Monroe, J. Grey, et al.
(författare)
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Mutation bias reflects natural selection in Arabidopsis thaliana
- 2022
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 602:7895, s. 101-105
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Tidskriftsartikel (refereegranskat)abstract
- Since the first half of the twentieth century, evolutionary theory has been dominated by the idea that mutations occur randomly with respect to their consequences(1). Here we test this assumption with large surveys of de novo mutations in the plant Arabidopsis thaliana. In contrast to expectations, we find that mutations occur less often in functionally constrained regions of the genome-mutation frequency is reduced by half inside gene bodies and by two-thirds in essential genes. With independent genomic mutation datasets, including from the largest Arabidopsis mutation accumulation experiment conducted to date, we demonstrate that epigenomic and physical features explain over 90% of variance in the genome-wide pattern of mutation bias surrounding genes. Observed mutation frequencies around genes in turn accurately predict patterns of genetic polymorphisms in natural Arabidopsis accessions (r = 0.96). That mutation bias is the primary force behind patterns of sequence evolution around genes in natural accessions is supported by analyses of allele frequencies. Finally, we find that genes subject to stronger purifying selection have a lower mutation rate. We conclude that epigenome-associated mutation bias2 reduces the occurrence of deleterious mutations in Arabidopsis, challenging the prevailing paradigm that mutation is a directionless force in evolution.
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| 4. |
- Snoeijs-Leijonmalm, Pauline, 1956-, et al.
(författare)
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Ecosystem mapping in the Central Arctic Ocean (CAO) during the SAS-Oden expedition : Final report
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- As a result of global warming, the marine ecosystem around the North Pole, the Central Arctic Ocean (CAO), is in fast transition from a permanently to a seasonally ice-covered ocean. The sea-ice loss is expected to enable summer access to the CAO for non-icebreaking ships, including fishery vessels, in the near future. However, the lack of knowledge on the CAO ecosystem impedes any assessment of the sustainability of potential future fisheries in the CAO. Taking a precautionary approach, the EU and nine countries in October 2018 signed the Agreement to Prevent Unregulated High Seas Fisheries in the Central Arctic Ocean. This agreement entered into force in June 2021 and a.o. requires the establishment of a joint scientific program to improve the understanding of the CAO ecosystem, including mapping and monitoring. To reduce the existing lack of knowledge, 12 scientists from the EFICA Consortium participated, together with 26 other on-board scientists, in sampling and data collection of ecosystem data during the Swedish SAS-Oden expedition in summer 2021. This report describes the field work performed by the EFICA scientists using water-column acoustics, deep-sea optical observations, and fish, zooplankton, sediment otolith and eDNA sampling for targeting fish, zooplankton and mammals. Further ecosystem data (physical, chemical and biological) were collected by the EFICA scientists in collaboration with other scientists on-board. Together with this report, a metadata database containing lists of all collected samples and data that are relevant for future fish-stock modelling and assessment studies was delivered to the European Commission.
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