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Dunning, Alison M,Michailidou, Kyriaki,Kuchenbaecker, Karoline B,Thompson, Deborah,French, Juliet D,Beesley, Jonathan,Healey, Catherine S,Kar, Siddhartha,Pooley, Karen A,Lopez-Knowles, Elena,Dicks, Ed Springer Science and Business Media LLC 2016 Nature genetics Vol.48 No.4
<P>We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor a) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER+ or ER-) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER-tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.</P>
TRANSATLANTIC FOREIGN DIRECT INVESTMENT AND THE EUROPEAN ECONOMIC COMMUNITY
DUNNING, JOHN H. 한국국제경제학회 1992 International Economic Journal Vol.6 No.1
This paper explores the isssue as to how far and in what way has European economic intergration ㅡand the prospects of completion of the internal market in 1992ㅡaffected the level and pattern of transatlantic value added activities. It is shown that the challenges of 1992 have revitalized U.S. investment in the European Community. At the same time, these same cahllenges, together with the wider imperatives of technological and globalization of production and markets, have encouraged and explosion of European direct investment in the United States.
A common coding variant in CASP8 is associated with breast cancer risk
Cox, Angela,Dunning, Alison M,Garcia-Closas, Montserrat,Balasubramanian, Sabapathy,Reed, Malcolm W R,Pooley, Karen A,Scollen, Serena,Baynes, Caroline,Ponder, Bruce A J,Chanock, Stephen,Lissowska, Jola Nature Pub. Co 2007 Nature genetics Vol.39 No.3
The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 −202 C → A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3′ UTR A → G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9–15 studies, comprising 11,391–18,290 cases and 14,753–22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85–0.94) and 0.74 (95% c.i.: 0.62–0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P<SUB>trend</SUB> = 1.1 × 10<SUP>−7</SUP>) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02–1.13) and 1.16 (95% c.i.: 1.08–1.25), respectively; P<SUB>trend</SUB> = 2.8 × 10<SUP>−5</SUP>). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.
Genome-wide association study identifies novel breast cancer susceptibility loci
Easton, Douglas F.,Pooley, Karen A.,Dunning, Alison M.,Pharoah, Paul D. P.,Thompson, Deborah,Ballinger, Dennis G.,Struewing, Jeffery P.,Morrison, Jonathan,Field, Helen,Luben, Robert,Wareham, Nicholas Nature Publishing Group 2007 Nature Vol.447 No.7148
Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r<SUP>2</SUP> > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10<SUP>-7</SUP>). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.
Wei Chun Wang,Bodil Rasmussen,Anthony Lin Zhang,Li-Wei Lin,Trisha Dunning,강승완,Byung-Joo Park,Sing Kai Lo 사단법인약침학회 2009 Journal of Acupuncture & Meridian Studies Vol.2 No.3
Objective: This systematic review aimed to critically appraise published clinical trials designed to assess the effect of Tai Chi on psychosocial well-being. Data Sources: Databases searched included MEDLINE, CINAHL, EMBASE, HEALT, PsycINFO, CISCOM, the Cochrane Central Register of Controlled Trials of the Cochrane Library, and dissertations and conference proceedings from inception to August 2008. Review Methods: Methodological quality was assessed using a modified Jadad scale. A total of 15 studies met the inclusion criteria (i.e. English publications of randomized controlled trials with Tai Chi as an intervention and psychological well-being as an outcome measure), of which eight were high quality trials. The psychosocial outcomes measured included anxiety (eight studies), depression (eight studies), mood (four studies), stress (two studies), general mental health three studies), anger, positive and negative effect, self-esteem, life satisfaction, social interaction and self-rated health (one study each). Results: Tai Chi intervention was found to have a significant effect in 13 studies, especially in the management of depression and anxiety. Although the results seemed to suggest Tai Chi is effective, they should be interpreted cautiously as the quality of the trials varied substantially. Furthermore, significant findings were shown in only six high quality studies. Moreover, significant between group differences after Tai Chi intervention was demonstrated in only one high quality study (the other three significant results were observed in non-high quality studies). Two high quality studies in fact found no significant Tai Chi effects. Conclusion: It is still premature to make any conclusive remarks on the effect of Tai Chi on psychosocial well-being. Objective: This systematic review aimed to critically appraise published clinical trials designed to assess the effect of Tai Chi on psychosocial well-being. Data Sources: Databases searched included MEDLINE, CINAHL, EMBASE, HEALT, PsycINFO, CISCOM, the Cochrane Central Register of Controlled Trials of the Cochrane Library, and dissertations and conference proceedings from inception to August 2008. Review Methods: Methodological quality was assessed using a modified Jadad scale. A total of 15 studies met the inclusion criteria (i.e. English publications of randomized controlled trials with Tai Chi as an intervention and psychological well-being as an outcome measure), of which eight were high quality trials. The psychosocial outcomes measured included anxiety (eight studies), depression (eight studies), mood (four studies), stress (two studies), general mental health three studies), anger, positive and negative effect, self-esteem, life satisfaction, social interaction and self-rated health (one study each). Results: Tai Chi intervention was found to have a significant effect in 13 studies, especially in the management of depression and anxiety. Although the results seemed to suggest Tai Chi is effective, they should be interpreted cautiously as the quality of the trials varied substantially. Furthermore, significant findings were shown in only six high quality studies. Moreover, significant between group differences after Tai Chi intervention was demonstrated in only one high quality study (the other three significant results were observed in non-high quality studies). Two high quality studies in fact found no significant Tai Chi effects. Conclusion: It is still premature to make any conclusive remarks on the effect of Tai Chi on psychosocial well-being.
Han, Donghee,Hartaigh, Brí,ain Ó,Gransar, Heidi,Lee, Ji Hyun,Rizvi, Asim,Baskaran, Lohendran,Schulman-Marcus, Joshua,Dunning, Allison,Achenbach, Stephan,Al-Mallah, Mouaz H,Berman, Daniel S Oxford University Press 2018 European heart journal cardiovascular Imaging Vol.19 No.6
<P><B>Abstract</B></P><P><B>Aims</B></P><P>Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults.</P><P><B>Methods and results</B></P><P>Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1–49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18–41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, <I>P</I>-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; <I>P</I>-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles.</P><P><B>Conclusion</B></P><P>CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults.</P>
Five polymorphisms and breast cancer risk: results from the Breast Cancer Association Consortium.
Gaudet, Mia M,Milne, Roger L,Cox, Angela,Camp, Nicola J,Goode, Ellen L,Humphreys, Manjeet K,Dunning, Alison M,Morrison, Jonathan,Giles, Graham G,Severi, Gianluca,Baglietto, Laura,English, Dallas R,Cou American Association for Cancer Research 2009 Cancer Epidemiology, Biomarkers & Prevention Vol.18 No.5
<P>Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent.</P>
Han, Mi-Ryung,Zheng, Wei,Cai, Qiuyin,Gao, Yu-Tang,Zheng, Ying,Bolla, Manjeet K.,Michailidou, Kyriaki,Dennis, Joe,Wang, Qin,Dunning, Alison M.,Brennan, Paul,Chen, Shou-Tung,Choi, Ji-Yeob,Hartman, Mikae Oxford University Press 2017 Carcinogenesis Vol.38 No.5
<P>Over the past 20 years, high-penetrance pathogenic mutations in genes BRCA1, BRCA2, TP53, PTEN, STK11 and CDH1 and moderate-penetrance mutations in genes CHEK2, ATM, BRIP1, PALB2, RAD51C, RAD50 and NBN have been identified for breast cancer. In this study, we investigated whether there are additional variants in these 13 genes associated with breast cancer among women of Asian ancestry. We analyzed up to 654 single nucleotide polymorphisms (SNPs) from 6269 cases and 6624 controls of Asian descent included in the Breast Cancer Association Consortium (BCAC), and up to 236 SNPs from 5794 cases and 5529 controls included in the Shanghai Breast Cancer Genetics Study (SBCGS). We found three missense variants with minor allele frequency (MAF) < 0.05: rs80358978 (Gly2508Ser), rs80359065 (Lys2729Asn) and rs11571653 (Met784Val) in the BRCA2 gene, showing statistically significant associations with breast cancer risk, with P-values of 1.2 x 10(-4), 1.0 x 10(-3) and 5.0 x 10(-3), respectively. In addition, we found four low-frequency variants (rs8176085, rs799923, rs8176173 and rs8176258) in the BRCA1 gene, one common variant in the CHEK2 gene (rs9620817), and one common variant in the PALB2 gene (rs13330119) associated with breast cancer risk at P < 0.01. Our study identified several new risk variants in BRCA1, BRCA2, CHEK2, and PALB2 genes in relation to breast cancer risk in Asian women. These results provide further insights that, in addition to the high/moderate penetrance mutations, other low-penetrance variants in these genes may also contribute to breast cancer risk.</P>
The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers
Amos, Christopher I.,Dennis, Joe,Wang, Zhaoming,Byun, Jinyoung,Schumacher, Fredrick R.,Gayther, Simon A.,Casey, Graham,Hunter, David J.,Sellers, Thomas A.,Gruber, Stephen B.,Dunning, Alison M.,Michail American Association for Cancer Research 2017 Cancer epidemiology, biomarkers & prevention Vol.26 No.1
<P>Impact: Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. (C)2016 AACR.</P>