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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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- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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- Stevens, Kristen N, et al.
(författare)
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19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
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Tidskriftsartikel (refereegranskat)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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- Schewe, Jacob, et al.
(författare)
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State-of-the-art global models underestimate impacts from climate extremes
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Global impact models represent process-level understanding of how natural and human systems may be affected by climate change. Their projections are used in integrated assessments of climate change. Here we test, for the first time, systematically across many important systems, how well such impact models capture the impacts of extreme climate conditions. Using the 2003 European heat wave and drought as a historical analogue for comparable events in the future, we find that a majority of models underestimate the extremeness of impacts in important sectors such as agriculture, terrestrial ecosystems, and heat-related human mortality, while impacts on water resources and hydropower are overestimated in some river basins; and the spread across models is often large. This has important implications for economic assessments of climate change impacts that rely on these models. It also means that societal risks from future extreme events may be greater than previously thought.
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A research agenda for tourism geographies
- 2019
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- In recent years, tourism geographies have developed into a vibrant field of research at the intersection of geography and tourism studies. The book presents a unique collection of individual research agendas aiming to inspire the pursuit of new avenues of research. Although there have been arguments to apply post-disciplinary perspectives within tourism research, this book highlights the interest and potential of tourism geographers to contribute to a geographical tradition and influence the future content of geography as a discipline.
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- Abbasian, Saeid, 1961-, et al.
(författare)
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Displaced diaspora second-home tourism : an explorative study of Swedish-Iranians and their second-home purchases in Turkey
- 2019
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Ingår i: Tourism. - Zagreb : Institute for Tourism. - 1332-7461 .- 1849-1545. ; 67:3, s. 239-252
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Tidskriftsartikel (refereegranskat)abstract
- This explorative study aims to gain more insight into Swedish-Iranians' purchase of second homes in Turkey. The study is based on 22 questionnaires (19 of them from owners and buyers), field observation, and participant observation. Motives behind owners' and buyers' purchases are: other Swedish-Iranian friends/relatives bought there; cultural proximity; absence of visa restriction for Iranian citizens; geographical proximity to Iran and relatives living in Iran; economic factors, including the low prices and costs and investment for retirement; and the climate. The respondents are well-integrated into Swedish society and have access to different types of resources which facilitate the purchase, but they also show the potential to partially become integrated socioculturally into their Turkish communities. A meaningful proportion of them are seriously planning to live permanently in Turkey after retirement, but the majority stay there for longer periods or semi-permanently. Despite some limitations, this study makes an important contribution to the area of diaspora second-home tourism and to the field of diaspora studies.
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- Abbasian, Saeid, 1961-, et al.
(författare)
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Second Home purchase in Turkey by Swedish Iranians : An Explorative Study
- 2017
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Ingår i: 26th Nordic Symposium of Tourism and Hospitality Research October 4-6 2017, Falun, Sweden.
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Konferensbidrag (refereegranskat)abstract
- Second home tourism is often discussed in the context of the western world. Other groups and their motivations, in this case people of Iranian background who are a large ethnic group in Sweden, are often neglected, although the group has shown interest in purchase of second home in Turkey.The aim of this study is to get more insight on Swedish Iranians’ purchase of second home in Turkey. 19 e-mail interviews (with Broker companies, owners, and potentially buyers) have been conducted. Also participant observation in Antalya region in June 2015 and at the exhibition of “Buying Properties Abroad” in Kista in September 2015 has been done.The interview results reveal that the Swedish Iranian second home buyers collect information through friends and relatives, various web sites, exhibitions, brokers, and real estate companies before buying apartment. Their motives have been: following other friends/relatives who bought apartments there, cultural proximity including the Turkish language and food, geographic proximity to Iran, relatives living in Iran do not need Turkish visa, economic factors including prices, the climate, and investment for the retirement. They stay in their apartments at least once a year up to 4 times a year and the duration of their stay each time is at least one week. A part of them might choose to live partly or permanently in Turkey after the retirement. Their motives are similar to many other second home owners elsewhere but there are also aspects related to the political context of this mobility.
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