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| 44. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 46. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 47. |
- Brohet, Richard M., et al.
(författare)
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Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: A report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group
- 2007
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 25:25, s. 3831-3836
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Earlier studies have shown that endogenous gonadal hormones play an important role in the etiology of breast cancer among BRCA1/ 2 mutation carriers. So far, little is known about the safety of exogenous hormonal use in mutation carriers. In this study, we examined the association between oral contraceptive use and risk of breast cancer among BRCA1/ 2 carriers. Patients and Methods In the International BRCA1/ 2 Carrier Cohort study ( IBCCS), a retrospective cohort of 1,593 BRCA1/ 2 mutation carriers was analyzed with a weighted Cox regression analysis. Results We found an increased risk of breast cancer for BRCA1/ 2 mutation carriers who ever used oral contraceptives ( adjusted hazard ratio [ HR] = 1.47; 95% CI, 1.16 to 1.87). HRs did not vary according to time since stopping use, age at start, or calendar year at start. However, a longer duration of use, especially before first full- term pregnancy, was associated with an increased risk of breast cancer for both BRCA1 and BRCA2 mutation carriers ( 4 or more years of use before first full-term pregnancy: HR = 1.49 [ 95% CI, 1.05 to 2.11] for BRCA1 carriers and HR = 2.58 [ 95% CI, 1.21 to 5.49] for BRCA2 carriers). Conclusion No evidence was found among BRCA1/ 2 mutation carriers that current use of oral contraceptives is associated with risk of breast cancer more strongly than is past use, as is found in the general population. However, duration of use, especially before first full- term pregnancy, may be associated with an increasing risk of breast cancer among both BRCA1 and BRCA2 mutation carriers.
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| 48. |
- Chang-Claude, Jenny, et al.
(författare)
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Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study
- 2007
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Ingår i: Cancer Epidemiology Biomarkers and Prevention. - 1055-9965. ; 16:4, s. 740-746
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early menarche and late menopause are important risk factors for breast cancer, but their effects on breast cancer risk in BRCA1 and BRCA2 carriers are unknown. Methods: We assessed breast cancer risk in a large series of 1,187 BRCA1 and 414 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study. Rate ratios were estimated using a weighted Cox-regression approach. Results: Breast cancer risk was not significantly related to age at menopause {hazard ratio [HR] for menopause below age 35 years, 0.60 [95% confidence interval (95% CI), 0.25-1.44]; 35 to 40 years, 1.15 [0.65-2.04]; 45 to 54 years, 1.02 [0.65-1.60]; ≥55 years, 1.12 [0.12-5.02], as compared with premenopausal women}. However, there was some suggestion of a reduction in risk after menopause in BRCA2 carriers. There was some evidence of a protective effect of oophorectomy (HR, 0.56; 95% CI, 0.29-1.09) and a significant trend of decreasing risk with increasing time since oophorectomy, but no apparent effect of natural menopause. There was no association between age at menarche and breast cancer risk, nor any apparent association with the estimated total duration of breast mitotic activity. Conclusions: These results are consistent with other observations suggesting a protective effect of oophorectomy, similar in relative effect to that in the general population. The absence of an effect of age at natural menopause is, however, not consistent with findings in the general population and may reflect the different natural history of the disease in carriers.
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| 49. |
- Clausen, Frederik Banch, et al.
(författare)
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Recommendation for validation and quality assurance of non-invasive prenatal testing for foetal blood groups and implications for IVD risk classification according to EU regulations
- 2022
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 117:2, s. 157-165
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Forskningsöversikt (refereegranskat)abstract
- Background and Objectives: Non-invasive assays for predicting foetal blood group status in pregnancy serve as valuable clinical tools in the management of pregnancies at risk of detrimental consequences due to blood group antigen incompatibility. To secure clinical applicability, assays for non-invasive prenatal testing of foetal blood groups need to follow strict rules for validation and quality assurance. Here, we present a multi-national position paper with specific recommendations for validation and quality assurance for such assays and discuss their risk classification according to EU regulations. Materials and Methods: We reviewed the literature covering validation for in-vitro diagnostic (IVD) assays in general and for non-invasive foetal RHD genotyping in particular. Recommendations were based on the result of discussions between co-authors. Results: In relation to Annex VIII of the In-Vitro-Diagnostic Medical Device Regulation 2017/746 of the European Parliament and the Council, assays for non-invasive prenatal testing of foetal blood groups are risk class D devices. In our opinion, screening for targeted anti-D prophylaxis for non-immunized RhD negative women should be placed under risk class C. To ensure high quality of non-invasive foetal blood group assays within and beyond the European Union, we present specific recommendations for validation and quality assurance in terms of analytical detection limit, range and linearity, precision, robustness, pre-analytics and use of controls in routine testing. With respect to immunized women, different requirements for validation and IVD risk classification are discussed. Conclusion: These recommendations should be followed to ensure appropriate assay performance and applicability for clinical use of both commercial and in-house assays.
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| 50. |
- Dawson, Michael N., et al.
(författare)
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A second horizon scan of biogeography: Golden ages, Midas touches, and the Red Queen
- 2016
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Ingår i: Frontiers of Biogeography. - : University of California. - 1948-6596. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Are we entering a new 'Golden Age' of biogeography, with continued development of infrastructure and ideas? We highlight recent developments, and the challenges and opportunities they bring, in light of the snapshot provided by the 7th biennial meeting of the International Biogeography Society (IBS 2015). We summarize themes in and across 15 symposia using narrative analysis and word clouds, which we complement with recent publication trends and 'research fronts'. We find that biogeography is still strongly defined by core sub-disciplines that reflect its origins in botanical, zoological (particularly bird and mammal), and geographic (e.g., island, montane) studies of the 1800s. That core is being enriched by large datasets (e.g. of environmental variables, 'omics', species' occurrences, traits) and new techniques (e.g., advances in genetics, remote sensing, modeling) that promote studies with increasing detail and at increasing scales; disciplinary breadth is being diversified (e.g., by developments in paleobiogeography and microbiology) and integrated through the transfer of approaches and sharing of theory (e.g., spatial modeling and phylogenetics in evolutionary-ecological contexts). Yet some subdisciplines remain on the fringe (e.g., marine biogeography, deep-time paleobiogeography), new horizons and new theory may be overshadowed by popular techniques (e.g., species distribution modelling), and hypotheses, data, and analyses may each be wanting. Trends in publication suggest a shift away from traditional biogeography journals to multidisciplinary or open access journals. Thus, there are currently many opportunities and challenges as biogeography increasingly addresses human impacts on, and stewardship of, the planet (e.g., Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services). As in the past, biogeographers doubtless will continue to be engaged by new data and methods in exploring the nexus between biology and geography for decades into the future. But golden ages come and go, and they need not touch every domain in a discipline nor affect subdisciplines at the same time; moreover, what appears to be a Golden Age may sometimes have an undesirable 'Midas touch'. Contexts within and outwith biogeography-e.g., methods, knowledge, climate, biodiversity, politics-are continually changing, and at times it can be challenging to establish or maintain relevance. In so many races with the Red Queen, we suggest that biogeography will enjoy greatest success if we also increasingly engage with the epistemology of our discipline.
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