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Sökning: WFRF:(Conner Thomas)

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  • Milne, Roger L, et al. (författare)
  • Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.
  • 2017
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 49:12, s. 1767-1778
  • Tidskriftsartikel (refereegranskat)abstract
    • Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
  • Phelan, Catherine M, et al. (författare)
  • Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.
  • 2017
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 49:5, s. 680-691
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
  • Brennan, Donal, et al. (författare)
  • The transcription factor Sox11 is a prognostic factor for improved recurrence-free survival in epithelial ovarian cancer
  • 2009
  • Ingår i: European Journal of Cancer. - IFAC & Elsevier Ltd.. - 1879-0852. ; 45:8, s. 1510-1517
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Background: Current prognostic molecular markers for epithelial ovarian cancer (EOC) are insufficient. The aim of the current study was to investigate the role of Sox11 in EOC Methods: Using an in silico transcriptomic screen Sox11 was identified as a potential EOC biomarker. Sox11 protein expression was evaluated using immunohistochemistry (IHC) in 76 EOC cases, which were analyzed using automated algorithms to develop a quantitative scoring model. Results: Sox11 mRNA expression was up-regulated in EOC compared to normal tissues. Automated analysis of Sox11 in the EOC cohort revealed high expression of Sox11, in 40% of tumours, who had an improved recurrence free survival (RFS) (p= 0.002). Multivariate analysis confirmed Sox11 was an independent predictor of improved RFS after controlling for stage and grade. Conclusions: These data suggest that Sox11 is a new prognostic marker in EOC. Loss of SOX 11 is associated with a decreased RFS and a more aggressive phenotype.
  • Gering, Eben, et al. (författare)
  • Getting Back to Nature: Feralization in Animals and Plants
  • 2019
  • Ingår i: Trends in Ecology & Evolution. - ELSEVIER SCIENCE LONDON. - 0169-5347. ; 34:12, s. 1137-1151
  • Forskningsöversikt (övrigt vetenskapligt)abstract
    • Formerly domesticated organisms and artificially selected genes often escape controlled cultivation, but their subsequent evolution is not well studied. In this review, we examine plant and animal feralization through an evolutionary lens, including how natural selection, artificial selection, and gene flow shape feral genomes, traits, and fitness. Available evidence shows that feralization is not a mere reversal of domestication. Instead, it is shaped by the varied and complex histories of feral populations, and by novel selection pressures. To stimulate further insight we outline several future directions. These include testing how domestication genes act in wild settings, studying the brains and behaviors of feral animals, and comparative analyses of feral populations and taxa. This work offers feasible and exciting research opportunities with both theoretical and practical applications.
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