| 1. |
- Purrington, Kristen S., et al.
(författare)
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Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer
- 2014
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:5, s. 1012-1019
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Tidskriftsartikel (refereegranskat)abstract
- In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
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| 2. |
- Goodfellow, Bradley W., et al.
(författare)
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Arctic-alpine blockfields in the northern Swedish Scandes : late Quaternary - not Neogene
- 2014
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Ingår i: Earth Surface Dynamics. - : Copernicus GmbH. - 2196-6311 .- 2196-632X. ; 2:2, s. 383-401
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Tidskriftsartikel (refereegranskat)abstract
- Autochthonous blockfield mantles may indicate alpine surfaces that have not been glacially eroded. These surfaces may therefore serve as markers against which to determine Quaternary erosion volumes in adjacent glacially eroded sectors. To explore these potential utilities, chemical weathering features, erosion rates, and regolith residence durations of mountain blockfields are investigated in the northern Swedish Scandes. This is done, firstly, by assessing the intensity of regolith chemical weathering along altitudinal transects descending from three blockfield-mantled summits. Clay / silt ratios, secondary mineral assemblages, and imaging of chemical etching of primary mineral grains in fine matrix are each used for this purpose. Secondly, erosion rates and regolith residence durations of two of the summits are inferred from concentrations of in situ-produced cosmogenic Be-10 and Al-26 in quartz at the blockfield surfaces. An interpretative model is adopted that includes temporal variations in nuclide production rates through surface burial by glacial ice and glacial isostasy-induced elevation changes of the blockfield surfaces. Together, our data indicate that these blockfields are not derived from remnants of intensely weathered Neogene weathering profiles, as is commonly considered. Evidence for this interpretation includes minor chemical weathering in each of the three examined blockfields, despite consistent variability according to slope position. In addition, average erosion rates of similar to 16.2 and similar to 6.7 mm ka(-1), calculated for the two blockfield-mantled summits, are low but of sufficient magnitude to remove present blockfield mantles, of up to a few metres in thickness, within a late Quaternary time frame. Hence, blockfield mantles appear to be replenished by regolith formation through, primarily physical, weathering processes that have operated during the Quaternary. The persistence of autochthonous blockfields over multiple glacial-interglacial cycles confirms their importance as key markers of surfaces that were not glacially eroded through, at least, the late Quaternary. However, presently blockfield-mantled surfaces may potentially be subjected to large spatial variations in erosion rates, and their Neogene regolith mantles may have been comprehensively eroded during the late Pliocene and early Pleistocene. Their role as markers by which to estimate glacial erosion volumes in surrounding landscape elements therefore remains uncertain.
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| 3. |
- Goodfellow, Bradley W., et al.
(författare)
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Controls of tor formation, Cairngorm Mountains, Scotland
- 2014
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Ingår i: Journal Of Geophysical Research: Earth Surface. - 2169-9003. ; 119:2, s. 225-246
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Tidskriftsartikel (refereegranskat)abstract
- Tors occur in many granitic landscapes and provide opportunities to better understand differential weathering. We assess tor formation in the Cairngorm Mountains, Scotland, by examining correlation of tor location and size with grain size and the spacing of steeply dipping joints. We infer a control on these relationships and explore its potential broader significance for differential weathering and tor formation. We also assess the relationship between the formation of subhorizontal joints in many tors and local topographic shape by evaluating principle surface curvatures from a digital elevation model of the Cairngorms. We then explore the implications of these joints for tor formation. We conclude that the Cairngorm tors have formed in kernels of relatively coarse grained granite. Tor volumes increase with grain size and the spacing of steeply dipping joints. We infer that the steeply dipping joints largely formed during pluton cooling and are more widely spaced in tor kernels because of slower cooling rates. Preferential tor formation in coarser granite with a wider joint spacing that is more easily grusified indicates that joint spacing is a dominant control on differential weathering. Sheet jointing is well developed in tors located on relatively high convex surfaces. This jointing formed after the gross topography of the Cairngorms was established and before tor emergence. The presence of closely spaced (tens of centimeters), subhorizontal sheeting joints in tors indicates that these tors, and similarly sheeted tors elsewhere, formed either after subaerial exposure of bedrock or have progressively emerged from a regolith only a few meters thick. Key Points Tors form in kernels of coarse-grained granite among finer-grained granite Wide joint spacing in tors attributable to a slow cooling rate of the granite Sheet jointing discounts tor formation within a thick regolith
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| 4. |
- Haiman, Christopher A., et al.
(författare)
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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:12, s. 61-1210
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
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