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4. De la Ausencia a la presencia. 'Nuevas' Formas de gestión de la Alteridad en el Marco del Desarrollo

Author

Olver B. Quijano Valencia

Subjects
Political science, Social sciences (General), H1-99
Abstract

Al inscribirse en la reconfiguración histórica del poder, la reflexión considera la relación alteridad y desarrollo, destacando los cambios cualitativos de los dispositivos de dominación, soportados en principio, alrededor de políticas y prácticas de invisibilización; posteriormente, bajo la asimilación o reducción y actualmente en los dictados de la eclosión de la alteridad o la economía de las visibilidades. Se reconoce el intento por llenar de contenido la política de la diferencia o discriminación positiva, en el marco del reordenamiento de fuerzas y movimiento sociales, bajo un amplio capital simbólico con capacidad para contraponerse a la dominación mundial, construyendo imaginarios de desarrollo en favor de la vida, la cultura y el conocimiento local.

Published
2002

8. Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups (Retraction of vol 118, pg 5211, 2011)

Author

Huang, X., Kushekhar, K., Nolte, Roeland J. M., Kooistra, W., Visser, Lydia, Bouwman, Ilby, Kouprie, N., Veenstra, R., van Imhoff, G., Imhoff, G., Olver, B., Houlston, R. S., Poppema, S., Diepstra, A., Hepkema, B., van den Berg, A., Stem Cell Aging Leukemia and Lymphoma (SALL), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Published
2012

9. The avifauna of Kwandwe Private Game Reserve, Eastern Cape, South Africa

Author

Craig, A.J.F.K., Bissett, C., Galpin, M.D., Olver, B., and Hulley, P.E.

Abstract

A protected area since 1999, Kwandwe Private Game Reserve incorporates several former farms, for which past records of bird occurrences are available. No bird species appear to have been lost from the area. Between 2001 and 2005, a group of observers conducted systematic bird surveys in most months, which allowed the status (resident, migrant or irregular visitor) of most bird species to be determined. At least three species have established breeding populations in the reserve over the past 10 years. Of 302 species reliably recorded to date, 182 (60.3%) appear to be resident, 46 (15.2%) are seasonal migrants and 74 (24.5%) are vagrant visitors. Eight vulnerable and eight near-threatened bird species have been recorded; Blue Crane, Kori Bustard and African Crowned Eagle have bred in the reserve. Together with other state-owned and private protected areas in this region, this reserve holds a significant portion of the inland bird species recorded from the Eastern Cape. CONSERVATION IMPLICATIONS: The varied thicket vegetation types of the Great Fish River Valley support a considerable diversity of bird species. If these habitats are managed for biodiversity conservation, they can support a large component of the terrestrial avifauna of the Eastern Cape region.

Published
2011

11. Visiones y prácticas de diferencia económico/cultural en contextos de multiplicidad

Author

Quijano Valencia, Olver B. and Lander, Edgardo, dir.

Subjects
MISAK, ECONOMÍA AGRÍCOLA, INDÍGENAS DE COLOMBIA, INTERCULTURALIDAD, CULTURA INDÍGENA, MODERNIDAD
Abstract

La presente aventura analítica como toda iniciativa académica e intelectual, constituye una batalla por la producción de significados específicos sobre un fenómeno concreto y desde el prohijamiento de singulares horizontes epistémico/políticos, esta vez apelando de una parte a importantes pero siempre insuficientes referentes teóricos, y de otro lado al examen de cómo tales asunciones son o requieren ser localizadas, experimentadas y practicadas. La reivindicación en este trabajo de ciertas visiones y prácticas económico/culturales, se inscribe en agendas que identifican la diferencia como parte del imaginario teórico y político contemporáneo, a la vez que la reconocen como fuente de inteligibilidad, esperanza y posibilidad de articulación de proyectos emancipatorios y no como apelación y práctica de impunidad que posiciona lo diferente sólo como positividad, ´algo bueno´ y lugar no problemático. La concreción de los propósitos del trabajo se mueve en principio a través de una aproximación/revisión crítica a posturas representativas de la modernidad en el contexto latinoamericano, donde su pretendida universalización y naturalización soslaya la multiplicidad de ´topografías diferentes de la modernidad´ ancladas en la diferencia. Con todo esto y siendo una consideración ineluctable, importa el examen a la relación/tensión y articulación entre desarrollo, economía y cultura, triada con entronques a formas de dominio imperial/colonial y de geopolítica global que desconoce otras expresiones, significaciones y representaciones configuradas a partir de singularidades, urgencias locales y la valoración de la diferencia económico/cultural en contextos globalocalizados. En este esfuerzo deductivo, reivindicar la diferencia económico/cultural parte ─sin ser un ortodoxo ejercicio económico─, de mostrar cómo la economía representa una manifestación del proyecto moderno/imperial/colonial, al concebirse como disciplina y práctica totalizante/universal, desde donde, de una parte ha sido imposible el análisis y (re)conocimiento de otras formas de pensar y practicar la realidad económico/cultural, y de otra se han integrado/reducido diversas formas de relación al repertorio capitalogocentrista de la economía (neo)clásica. El ejercicio al presentar no el panorama de lo posible sino ante todo el horizonte y el flujo de lo existente en términos de visiones y prácticas de diferencia económico/cultural, se suma a otros esfuerzos orientados a proporcionar elementos ya no para pensar y construir economías diversas u otras economías, sino ante todo para constatar, visibilizar y movilizar estas expresiones lugarizadas, inscritas sin duda en el marco de la inflexión decolonial o en la perspectiva que promueve también la descolonización de la economía política (versión clásica y marxista) y de la economía formal (versión neoclásica y sus variantes). Estas pretensiones, consideraciones y búsquedas son presentadas en el trabajo como un esfuerzo por rastrear críticamente temas y problemas como occidente, modernidad, desarrollo y economía, para luego a manera de constatación, concentrar el análisis en las visiones y prácticas económico/culturales en contextos de multiplicidad, esta vez en algunas organizaciones y movimientos del Cauca Indígena en Colombia como son el programa económico/ambiental del Consejo Regional Indígena del Cauca – Cric, el Tejido Económico/Ambiental de la Asociación de Cabildos Indígenas del Norte del Cauca Acin – Çxab Wala Kiwe–, y la perspectiva económica del pueblo Misak. La explicitación y análisis de referentes económico/culturales/territoriales en tales organizaciones y movimientos, se hace no como forma de confrontación en pro de posicionamientos vanguardistas frente a la economía hegemónica, sino como posibilidad de volver legibles, visibles e inteligibles visiones y prácticas de diferencia económico/cultural como expresión existencial de otros espacios/superficies, otros actores y de otro tipo de actuaciones. En suma, con estos soportes y desarrollos académicos/intelectuales, políticos y existenciales y en medio de nuestra epocalidad, el trabajo proporciona insumos para complejizar/intensificar los términos en que se debaten desde el pensamiento crítico, fenómenos como la diferencia en sus distintas expresiones y en medio de un mundo múltiple, vulnerable, litigioso, pero igualmente esperanzador. Desde la convicción acerca de que no hay universalismos antropológicos como tampoco económico/culturales, la modernidad, el desarrollo y la economía se asumen como gubernamentalidades, es decir como tecnologías de gobierno de los unos y de los otros, no obstante su interrelaciones e interfecundidades en los diversos escenarios físico/naturales y socio/culturales. Empero, también se trata de juegos discursivos que se movilizan sobre la multiplicidad con efectos ontológicos singulares en la constitución de mundos y modos que hablan de creaciones, efectuaciones y experimentaciones diversas. De esta manera, se reivindican movimientos y organizaciones sociales como comunidades de pensamiento, en cuyas agendas/agencias, de una parte, se ponen en tensión ciertos principios, asunciones, prácticas y valores modernos/imperiales, y de otro lado, se apuesta estratégicamente a una suerte de interfecundidad en la que, también la apelación a lo ´propio´ se asume y practica como forma de instrumentalización política de la singularidad socio/económica y cultural. Las prácticas de resistencia en el Cauca indígena, también se evidencian específicamente en los ´mandatos económico/ambientales´, los ´tejidos de economía y medio ambiente´, los ´Planes de Vida y la economía propia´, ´la economía, la pervivencia, el territorio y la vida´, el lugar y el territorio como superficies y móviles de la diferencia económico/cultural, las redes de reciprocidad y las formas singulares de redistribución, el imperativo de abstención de la acumulación, las expresiones particulares/diferenciales de producción y trabajo, el sistema de producción Nasa Tull/Ya Tull, los trueques o intercambios para la pervivencia de saberes, sabores y solidaridades, los mercados locales y la interculturización económica, la perspectiva económica plural, y entre otros, las relaciones entre economía y revitalización cultural como una misma cosa. En suma, el trabajo deja ver cómo en vez de esperar a que la revolución o el internacionalismo socialista, la globalización neo-liberal, las terceras vías, las fuerzas providenciales, los organismos multilaterales de crédito, las iglesias salvadoras y el capital filantrópico contemporáneo, instalaran e impulsaran las prácticas económico/culturales; los movimientos y comunidades indígenas del Departamento del Cauca Colombia en sus proyectos por ´recuperarlo todo´ y no obstante las condiciones socio/políticas y económicas adversas; continúan movilizando creativa y experimentalmente procesos, esfuerzos e iniciativas propios de ´discursos, visiones y prácticas de diferencia epistémica, política/ecológica, económico/cultural´, horizonte privilegiado para la recuperación de saberes, el fortalecimiento económico/cultural y los procesos autonómicos, siempre en favor de la Vida y en el marco de una suerte de ´minga de resistencia social y comunitaria´.

Published
2010

12. La transición paradigmática y los agenciamiento sociales latinoamericanos (Tema Central)

Author

Quijano Valencia, Olver B.

Subjects
TEORÍA CRÍTICA, DESARROLLO, FILOSOFÍA LATINOAMERICANA, MODERNIDAD
Abstract

A partir de las premisas sobre “reinventar la emancipación social” y “renovar la teoría crítica” como muestra de la denominada transición paradigmática de nuestro espacio/tiempo propuesta por B. De Sousa Santos, la refl exión presenta panorámicamente, alusiones al rol que juegan los procesos y agencias sociales en América Latina, los que paulatinamente impactan los planos socioeconómicos, político-culturales y epistemológicos, en medio de una especial cartografía de las singularidades, un nuevo clima político e intelectual propio de múltiples posiciones de sujeto y entre otros, un conjunto de agenciamientos que confrontan la lógica totalizadora y las hegemonías cognitivo-existenciales.

Published
2007

14. Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

Author

Dunlop, MG, Dobbins, SE, Farrington, SM, Jones, AM, Palles, C, Whiffin, N, Tenesa, A, Spain, S, Broderick, P, Ooi, L-Y, Domingo, E, Smillie, C, Henrion, M, Frampton, M, Martin, L, Grimes, G, Gorman, M, Semple, C, Ma, YP, Barclay, E, Prendergast, J, Cazier, J-B, Olver, B, Penegar, S, Lubbe, S, Chander, I, Carvajal-Carmona, LG, Ballereau, S, Lloyd, A, Vijayakrishnan, J, Zgaga, L, Rudan, I, Theodoratou, E, Starr, JM, Deary, I, Kirac, I, Kovacevic, D, Aaltonen, LA, Renkonen-Sinisalo, L, Mecklin, J-P, Matsuda, K, Nakamura, Y, Okada, Y, Gallinger, S, Duggan, DJ, Conti, D, Newcomb, P, Hopper, J, Jenkins, MA, Schumacher, F, Casey, G, Easton, D, Shah, M, Pharoah, P, Lindblom, A, Liu, T, Smith, CG, West, H, Cheadle, JP, Midgley, R, Kerr, DJ, Campbell, H, Tomlinson, IP, Houlston, RS, Dunlop, MG, Dobbins, SE, Farrington, SM, Jones, AM, Palles, C, Whiffin, N, Tenesa, A, Spain, S, Broderick, P, Ooi, L-Y, Domingo, E, Smillie, C, Henrion, M, Frampton, M, Martin, L, Grimes, G, Gorman, M, Semple, C, Ma, YP, Barclay, E, Prendergast, J, Cazier, J-B, Olver, B, Penegar, S, Lubbe, S, Chander, I, Carvajal-Carmona, LG, Ballereau, S, Lloyd, A, Vijayakrishnan, J, Zgaga, L, Rudan, I, Theodoratou, E, Starr, JM, Deary, I, Kirac, I, Kovacevic, D, Aaltonen, LA, Renkonen-Sinisalo, L, Mecklin, J-P, Matsuda, K, Nakamura, Y, Okada, Y, Gallinger, S, Duggan, DJ, Conti, D, Newcomb, P, Hopper, J, Jenkins, MA, Schumacher, F, Casey, G, Easton, D, Shah, M, Pharoah, P, Lindblom, A, Liu, T, Smith, CG, West, H, Cheadle, JP, Midgley, R, Kerr, DJ, Campbell, H, Tomlinson, IP, and Houlston, RS

Abstract

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

Published
2012

15. Multiple Common Susceptibility Variants near BMP Pathway Loci GREM1, BMP4, and BMP2 Explain Part of the Missing Heritability of Colorectal Cancer

Author

Gibson, G, Tomlinson, IPM, Carvajal-Carmona, LG, Dobbins, SE, Tenesa, A, Jones, AM, Howarth, K, Palles, C, Broderick, P, Jaeger, EEM, Farrington, S, Lewis, A, Prendergast, JGD, Pittman, AM, Theodoratou, E, Olver, B, Walker, M, Penegar, S, Barclay, E, Whiffin, N, Martin, L, Ballereau, S, Lloyd, A, Gorman, M, Lubbe, S, Howie, B, Marchini, J, Ruiz-Ponte, C, Fernandez-Rozadilla, C, Castells, A, Carracedo, A, Castellvi-Bel, S, Duggan, D, Conti, D, Cazier, J-B, Campbell, H, Sieber, O, Lipton, L, Gibbs, P, Martin, NG, Montgomery, GW, Young, J, Baird, PN, Gallinger, S, Newcomb, P, Hopper, J, Jenkins, MA, Aaltonen, LA, Kerr, DJ, Cheadle, J, Pharoah, P, Casey, G, Houlston, RS, Dunlop, MG, Gibson, G, Tomlinson, IPM, Carvajal-Carmona, LG, Dobbins, SE, Tenesa, A, Jones, AM, Howarth, K, Palles, C, Broderick, P, Jaeger, EEM, Farrington, S, Lewis, A, Prendergast, JGD, Pittman, AM, Theodoratou, E, Olver, B, Walker, M, Penegar, S, Barclay, E, Whiffin, N, Martin, L, Ballereau, S, Lloyd, A, Gorman, M, Lubbe, S, Howie, B, Marchini, J, Ruiz-Ponte, C, Fernandez-Rozadilla, C, Castells, A, Carracedo, A, Castellvi-Bel, S, Duggan, D, Conti, D, Cazier, J-B, Campbell, H, Sieber, O, Lipton, L, Gibbs, P, Martin, NG, Montgomery, GW, Young, J, Baird, PN, Gallinger, S, Newcomb, P, Hopper, J, Jenkins, MA, Aaltonen, LA, Kerr, DJ, Cheadle, J, Pharoah, P, Casey, G, Houlston, RS, and Dunlop, MG

Abstract

Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10)) and BMP2 (rs4813802, P = 4.65×10(-11)). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8)) and rs11632715 (P = 2.30×10(-10)). As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases.

Published
2011

16. Common genetic variation at 15q25.2 impacts on chronic lymphocytic leukaemia risk

Author

Crowther Swanepoel, D, Di Bernardo, Mc, Jamroziak, K, Karabon, L, Frydecka, I, Deaglio, S, D'Arena, G, Rossi, Dario, Gaidano, G, Olver, B, Lloyd, A, Broderick, P, Laurenti, Luca, Szemraj Rogucka, Z, Robak, T, Catovsky, D, Houlston, Rs, Laurenti, Luca (ORCID:0000-0002-8327-1396), Crowther Swanepoel, D, Di Bernardo, Mc, Jamroziak, K, Karabon, L, Frydecka, I, Deaglio, S, D'Arena, G, Rossi, Dario, Gaidano, G, Olver, B, Lloyd, A, Broderick, P, Laurenti, Luca, Szemraj Rogucka, Z, Robak, T, Catovsky, D, Houlston, Rs, and Laurenti, Luca (ORCID:0000-0002-8327-1396)

Abstract

A genome-wide association study of chronic lymphocytic leukaemia (CLL) suggested that common variants at 15q25.2 (rs783540) and 18q21.1 (rs1036935) influence CLL. To validate these associations and explore their relationship with CLL risk we genotyped case-control datasets from Poland, UK and Italy totalling 1428 cases and 1920 controls. Combined data from these and previously genotyped series (2503 cases and 5789 controls) provided evidence for an association between 15q25.2 and 18q21.1 loci and CLL risk (P(combined) = 1·10 × 10(-7) and 1·30 × 10(-5) respectively). These data provide further evidence for the involvement of common genetic variants in CLL risk and insight into the biological basis of disease development.

Published
2011

19. Synergy between EngE, XynA and ManA from Clostridium cellulovoranson corn stalk, grass and pineapple pulp substrates

Author

Olver, B., Dyk, J., Beukes, N., and Pletschke, B.

Abstract

The synergistic interaction between various hemi/cellulolytic enzymes has become more important in order to achieve effective and optimal degradation of complex lignocellulose substrates for biofuel production. This study investigated the synergistic effect of three enzymes endoglucanase (EngE), mannanase (ManA) and xylanase (XynA) on the degradation of corn stalk, grass, and pineapple fruit pulp and determined the optimal degree of synergy between combinations of these enzymes. It was established that EngE was essential for degradation of all of the substrates, while the hemicellulases were able to contribute in a synergistic fashion to increase the activity on these substrates. Maximum specific activity and degree of synergy on the corn stalk and grass was found with EngE:XynA in a ratio of 75:25%, with a specific activity of 41.1 U/mg protein and a degree of synergy of 6.3 for corn stalk, and 44.1 U/mg protein and 3.4 for grass, respectively. The pineapple fruit pulp was optimally digested using a ManA:EngE combination in a 50:50% ratio; the specific activity and degree of synergy achieved were 52.4 U/mg protein and 2.7, respectively. This study highlights the importance of hemicellulases for the synergistic degradation of complex lignocellulose. The inclusion of a mannanase in an enzyme consortium for biomass degradation should be examined further as this study suggests that it may play an important, although mostly overlooked, role in the synergistic saccharification of lignocellulose.

Published
2011
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20. Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk

Author

Davies, Fe, Jackson, Gh, Goldschmidt, H., Fo&#776, rsti, A., Hemminki, K., Broderick, P., Walker, Ba, Gregory, Wa, Neben, K., Hoffmann, P., Tomlinson, Ip, Moebus, S., Houlston, Rs, Mu&#776, hleisen, Tw, Chubb, D., Dobbins, Se, Weinhold, N., Olver, B., Child, Ja, Johnson, Dc, Ma, Yp, No&#776, then, Mm, Jauch, A., Lloyd, A., Morgan, Gj, and Ross, Fm

23. LETTERS.

Author

Brack, Ian, Huntington, Samuel, Moss, Vladimir, Nind, Philip, Khan, Rizwan, Hooper, Ibrahim, Brook, Chris, Nowrouzian, Gail, Page, Jennifer, Giuliani, Rudolph, Parsons, Anthony, Adamson, Adam, Lakin, Peter, Olver, B. W., Paton, Frank, Ahiram, Ephraim, Weedon, Basil, Snape, William, and Anderson, Tom

Subjects
*LETTERS to the editor, *ISLAM
Abstract

Presents a letter to the editor on matters related to the Islamic faith.

Published
1994

24. Inherited genetic susceptibility to monoclonal B-cell lymphocytosis

Author

Dalemari, Crowther-Swanepoel, Tanguy, Corre, Amy, Lloyd, Gianluca, Gaidano, Bianca, Olver, Fiona L, Bennett, Chi, Doughty, Daniela, Toniolo, Federico, Caligaris-Cappio, Federico, Calligaris-Cappio, Paolo, Ghia, Davide, Rossi, Andy C, Rawstron, Daniel, Catovsky, Richard S, Houlston, Crowther Swanepoel, D, Corre, T, Lloyd, A, Gaidano, G, Olver, B, Bennett, Fl, Doughty, C, Toniolo, D, Caligaris Cappio, F, Ghia, PAOLO PROSPERO, Rossi, D, Rawstron, Ac, Catovsky, D, and Houlston, Rs

Subjects
Male, Lymphocytosis, Genotype, Chronic lymphocytic leukemia, Immunology, Population, Single-nucleotide polymorphism, Biology, Biochemistry, Polymorphism, Single Nucleotide, Genetic predisposition, medicine, Chromosomes, Human, Humans, Genetic Predisposition to Disease, education, Aged, Chromosome Aberrations, education.field_of_study, B-Lymphocytes, Cell Biology, Hematology, medicine.disease, Case-Control Studies, Monoclonal, Monoclonal B-cell lymphocytosis, Female, medicine.symptom
Abstract

Monoclonal B-cell lymphocytosis (MBL) is detectable in > 3% of the general population. Recent data are compatible, at least in a proportion of cases, with MBL being a progenitor lesion for chronic lymphocytic leukemia (CLL) and a surrogate for inherited predisposition. Common single nucleotide polymorphisms (SNPs) at 2q13 (rs17483466), 2q37.1 (rs13397985), 2q37.3 (rs757978), 6p25.3 (rs872071), 8q24.21 (rs2456449), 11q24.1 (rs735665), 15q21.3 (rs7169431), 15q23 (rs7176508), 16q24.1 (rs305061), and 19q13.32 (rs11083846) have been shown to confer a modest but significant increase in CLL risk. To examine the impact of these 10 SNPs on MBL, we analyzed 3 case-control series totaling 419 cases and 1753 controls. An association between genotype and MBL risk was seen for 9 SNPs, 6 of which were statistically significant: rs17483466 (odds ratio [OR] =1.27; P = .02), rs13397985 (OR = 1.40; P = 1.72 × 10−3), rs757978 (OR = 1.38; P = .02), rs872071 (OR = 1.27; P = 7.75 × 10−3), rs2456449 (OR = 1.31; P = 3.14 × 10−3), and rs735665 (OR = 1.63; P = 6.86 × 10−6). Collectively, these data provide support for genetic variation influencing CLL risk through predisposition to MBL.

Published
2010

25. Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk.

Author

Dunlop MG, Dobbins SE, Farrington SM, Jones AM, Palles C, Whiffin N, Tenesa A, Spain S, Broderick P, Ooi LY, Domingo E, Smillie C, Henrion M, Frampton M, Martin L, Grimes G, Gorman M, Semple C, Ma YP, Barclay E, Prendergast J, Cazier JB, Olver B, Penegar S, Lubbe S, Chander I, Carvajal-Carmona LG, Ballereau S, Lloyd A, Vijayakrishnan J, Zgaga L, Rudan I, Theodoratou E, Starr JM, Deary I, Kirac I, Kovacević D, Aaltonen LA, Renkonen-Sinisalo L, Mecklin JP, Matsuda K, Nakamura Y, Okada Y, Gallinger S, Duggan DJ, Conti D, Newcomb P, Hopper J, Jenkins MA, Schumacher F, Casey G, Easton D, Shah M, Pharoah P, Lindblom A, Liu T, Smith CG, West H, Cheadle JP, Midgley R, Kerr DJ, Campbell H, Tomlinson IP, and Houlston RS

Subjects
Case-Control Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study methods, Humans, Colorectal Neoplasms genetics, Cyclin-Dependent Kinase Inhibitor p21 genetics, DNA Polymerase III genetics, Membrane Proteins genetics
Abstract

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

Published
2012
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26. FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma.

Author

Ma YP, van Leeuwen FE, Cooke R, Broeks A, Enciso-Mora V, Olver B, Lloyd A, Broderick P, Russell NS, Janus C, Ashworth A, Houlston RS, and Swerdlow AJ

Subjects
Adult, Age Factors, Breast Neoplasms complications, Breast Neoplasms etiology, Case-Control Studies, Female, Genetic Predisposition to Disease, Hodgkin Disease complications, Hodgkin Disease genetics, Humans, Middle Aged, Netherlands epidemiology, Precision Medicine, Risk, United Kingdom epidemiology, Breast Neoplasms genetics, Hodgkin Disease radiotherapy, Mammary Glands, Human radiation effects, Polymorphism, Single Nucleotide, Receptor, Fibroblast Growth Factor, Type 2 genetics
Abstract

Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin lymphoma (HL) have a highly increased risk of breast cancer. For personalized advice and follow-up regimens for patients, information is needed on how the radiotherapy-related risk is affected by other breast cancer risk factors. Genome-wide association studies have identified 14 independently replicated common single nucleotide polymorphisms that influence breast cancer risk. To examine whether these variants contribute to risk of radiation-associated breast cancer in HL, we analyzed 2 independent case-control series, from the United Kingdom and The Netherlands, totaling 693 HL patients, 232 with breast cancer and 461 without. rs1219648, which annotates the FGFR2 gene, was associated with risk in both series (combined per-allele odds ratio = 1.59, 95% confidence interval: 1.26-2.02; P = .000111). These data provide evidence that genetic variation in FGFR2 influences radiation-induced breast cancer risk.

Published
2012
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27. HLA associations in classical Hodgkin lymphoma: EBV status matters.

Author

Huang X, Kushekhar K, Nolte I, Kooistra W, Visser L, Bouwman I, Kouprie N, Veenstra R, van Imhoff G, Olver B, Houlston RS, Poppema S, Diepstra A, Hepkema B, and van den Berg A

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Case-Control Studies, Female, Gene Frequency, HLA Antigens immunology, Haplotypes, Histocompatibility Testing, Hodgkin Disease complications, Hodgkin Disease immunology, Hodgkin Disease virology, Humans, Infectious Mononucleosis complications, Infectious Mononucleosis immunology, Infectious Mononucleosis virology, Linkage Disequilibrium, Male, Middle Aged, White People, HLA Antigens genetics, Herpesvirus 4, Human physiology, Hodgkin Disease genetics, Infectious Mononucleosis genetics
Abstract

The pathogenesis of classical Hodgkin lymphoma (cHL) involves environmental and genetic factors. To explore the role of the human leukocyte antigen (HLA) genes, we performed a case-control genotyping study in 338 Dutch cHL patients using a PCR-based sequence-specific oligonucleotide probe (SSOP) hybridization approach. The allele frequencies were compared to HLA typings of more than 6,000 controls. The age of the cHL patients varied between 13 and 81 years with a median of 35 years. Nodular sclerosis subtype was the most common subtype (87%) and EBV was detected in 25% of the cHL patients. HLA-B5 was significantly increased and HLA-DR7 significantly decreased in the total cHL patient population as compared to controls. Two class II associations were observed to be specific for the EBV- cHL population with an increase of HLA-DR2 and HLA-DR5. Allele frequencies of HLA-A1, HLA-B37 and HLA-DR10 were significantly increased in the EBV+ cHL population; these alleles are in strong linkage disequilibrium and form a common haplotype in Caucasians. The allele frequency of HLA-A2 was significantly decreased in the EBV+ cHL population. Analysis of haplotypes with a frequency of >1% revealed a significant increase of HLA-A2-B7-DR2 in EBV- cHL as compared to controls. SSOP association analysis revealed significant differences between EBV+ and EBV- cHL patients for 19 probes that discriminate between HLA-A*01 and HLA-A*02. In conclusion, the HLA-A1 and HLA-A2 antigens and not specific single nucleotide variants shared by multiple alleles are responsible for the association with EBV+ cHL. Furthermore several new protective and predisposing HLA class I and II associations for the EBV+, the EBV- and the entire cHL population were identified.

Published
2012
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28. Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk.

Author

Broderick P, Chubb D, Johnson DC, Weinhold N, Försti A, Lloyd A, Olver B, Ma Y, Dobbins SE, Walker BA, Davies FE, Gregory WA, Childs JA, Ross FM, Jackson GH, Neben K, Jauch A, Hoffmann P, Mühleisen TW, Nöthen MM, Moebus S, Tomlinson IP, Goldschmidt H, Hemminki K, Morgan GJ, and Houlston RS

Subjects
Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Protein Serine-Threonine Kinases genetics, Risk Factors, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 7, Genetic Variation, Multiple Myeloma genetics
Abstract

To identify risk variants for multiple myeloma, we conducted a genome-wide association study of 1,675 individuals with multiple myeloma and 5,903 control subjects. We identified risk loci for multiple myeloma at 3p22.1 (rs1052501 in ULK4; odds ratio (OR) = 1.32; P = 7.47 × 10(-9)) and 7p15.3 (rs4487645, OR = 1.38; P = 3.33 × 10(-15)). In addition, we observed a promising association at 2p23.3 (rs6746082, OR = 1.29; P = 1.22 × 10(-7)). Our study identifies new genomic regions associated with multiple myeloma risk that may lead to new etiological insights., Competing Interests: Statement The authors declare no competing financial interests.

Published
2011
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29. Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups.

Author

Huang X, Kushekhar K, Nolte I, Kooistra W, Visser L, Bouwman I, Kouprie N, Veenstra R, van Imhoff G, Olver B, Houlston RS, Poppema S, Diepstra A, Hepkema B, and van den Berg A

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Epstein-Barr Virus Infections genetics, Epstein-Barr Virus Infections immunology, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Herpesvirus 4, Human isolation & purification, Herpesvirus 4, Human pathogenicity, Hodgkin Disease classification, Hodgkin Disease virology, Humans, Linkage Disequilibrium, Male, Middle Aged, Netherlands, Young Adult, Genes, MHC Class I, Genes, MHC Class II, Hodgkin Disease genetics, Hodgkin Disease immunology
Abstract

The pathogenesis of classical Hodgkin lymphoma (cHL) involves environmental and genetic factors. To explore the role of the human leukocyte antigen (HLA) genes, we performed a case-control genotyping study in 338 Dutch cHL patients and more than 5000 controls using a PCR-based sequence-specific oligonucleotide probe hybridization approach. HLA-A68 and HLA-DR11 (5) were significantly increased in the cHL patient population compared with the controls. Three class II associations were observed in the EBV(-) cHL population with an increase of HLA-DR15 (2) and a decrease of HLA-DR4 and HLA-DR7. Allele frequencies of HLA-A1, HLA-B37, and HLA-DR10 were significantly increased in the EBV(+) cHL population; these alleles are in strong linkage disequilibrium and form a common haplotype in whites. The allele frequency of HLA-A2 was significantly decreased in the EBV(+) cHL population. Sequence-specific oligonucleotide probe analysis revealed significant differences between EBV(+) and EBV(-) cHL patients for 19 probes that discriminate between HLA-A*01 and HLA-A*02. In conclusion, the HLA-A1 and HLA-A2 antigens and not specific single nucleotide variants shared by multiple alleles are responsible for the association with EBV(+) cHL. Furthermore, several new protective and predisposing HLA class I and II associations for the EBV(+), the EBV(-), and the entire cHL population were identified.

Published
2011
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30. Common variation at 10p12.31 near MLLT10 influences meningioma risk.

Author

Dobbins SE, Broderick P, Melin B, Feychting M, Johansen C, Andersson U, Brännström T, Schramm J, Olver B, Lloyd A, Ma YP, Hosking FJ, Lönn S, Ahlbom A, Henriksson R, Schoemaker MJ, Hepworth SJ, Hoffmann P, Mühleisen TW, Nöthen MM, Moebus S, Eisele L, Kosteljanetz M, Muir K, Swerdlow A, Simon M, and Houlston RS

Subjects
Genetic Loci, Genome-Wide Association Study, Humans, Male, Meningeal Neoplasms epidemiology, Meningioma epidemiology, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Risk, Chromosomes, Human, Pair 10 genetics, Genetic Predisposition to Disease, Meningeal Neoplasms genetics, Meningioma genetics, Transcription Factors genetics
Abstract

To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 × 10(-14)). This finding advances our understanding of the genetic basis of meningioma development., Competing Interests: Statement The authors declare no competing financial interests.

Published
2011
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31. Common genetic variation at 15q25.2 impacts on chronic lymphocytic leukaemia risk.

Author

Crowther-Swanepoel D, Di Bernardo MC, Jamroziak K, Karabon L, Frydecka I, Deaglio S, D'Arena G, Rossi D, Gaidano G, Olver B, Lloyd A, Broderick P, Laurenti L, Szemraj-Rogucka Z, Robak T, Catovsky D, and Houlston RS

Subjects
Aged, Case-Control Studies, Chromosomes, Human, Pair 18 genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Chromosomes, Human, Pair 15 genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics
Abstract

A genome-wide association study of chronic lymphocytic leukaemia (CLL) suggested that common variants at 15q25.2 (rs783540) and 18q21.1 (rs1036935) influence CLL. To validate these associations and explore their relationship with CLL risk we genotyped case-control datasets from Poland, UK and Italy totalling 1428 cases and 1920 controls. Combined data from these and previously genotyped series (2503 cases and 5789 controls) provided evidence for an association between 15q25.2 and 18q21.1 loci and CLL risk (P(combined) = 1·10 × 10(-7) and 1·30 × 10(-5) respectively). These data provide further evidence for the involvement of common genetic variants in CLL risk and insight into the biological basis of disease development., (© 2011 Blackwell Publishing Ltd.)

Published
2011
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32. Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer.

Author

Tomlinson IP, Carvajal-Carmona LG, Dobbins SE, Tenesa A, Jones AM, Howarth K, Palles C, Broderick P, Jaeger EE, Farrington S, Lewis A, Prendergast JG, Pittman AM, Theodoratou E, Olver B, Walker M, Penegar S, Barclay E, Whiffin N, Martin L, Ballereau S, Lloyd A, Gorman M, Lubbe S, Howie B, Marchini J, Ruiz-Ponte C, Fernandez-Rozadilla C, Castells A, Carracedo A, Castellvi-Bel S, Duggan D, Conti D, Cazier JB, Campbell H, Sieber O, Lipton L, Gibbs P, Martin NG, Montgomery GW, Young J, Baird PN, Gallinger S, Newcomb P, Hopper J, Jenkins MA, Aaltonen LA, Kerr DJ, Cheadle J, Pharoah P, Casey G, Houlston RS, and Dunlop MG

Subjects
Aged, Bone Morphogenetic Protein 2 metabolism, Bone Morphogenetic Protein 4 metabolism, Case-Control Studies, Colorectal Neoplasms metabolism, Gene Frequency, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Signal Transduction, Bone Morphogenetic Protein 2 genetics, Bone Morphogenetic Protein 4 genetics, Colorectal Neoplasms genetics, Genetic Predisposition to Disease, Intercellular Signaling Peptides and Proteins genetics
Abstract

Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10)) and BMP2 (rs4813802, P = 4.65×10(-11)). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8)) and rs11632715 (P = 2.30×10(-10)). As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases., Competing Interests: The authors have declared that no competing interests exist.

Published
2011
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33. Evaluation of germline BMP4 mutation as a cause of colorectal cancer.

Author

Lubbe SJ, Pittman AM, Matijssen C, Twiss P, Olver B, Lloyd A, Qureshi M, Brown N, Nye E, Stamp G, Blagg J, and Houlston RS

Subjects
Adult, Aged, Amino Acid Sequence, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Protein Structure, Tertiary, Sequence Alignment, Transforming Growth Factor beta genetics, Bone Morphogenetic Protein 4 genetics, Bone Morphogenetic Protein 4 metabolism, Colorectal Neoplasms genetics, Germ-Line Mutation genetics
Abstract

Transforming growth factor-β (TGF-β) signalling plays a key role in colorectal cancer (CRC). Bone morphogenetic protein-4 (BMP4) is a member of the TGF-β family of signal transduction molecules. To examine if germline mutation in BMP4 causes CRC we analysed 504 genetically enriched CRC cases (by virtue of early-onset disease, family history of CRC) for mutations in the coding sequence of BMP4. We identified three pathogenic mutations, p.R286X (g.8330C>T), p.W325C (g.8449G>T) and p.C373S (g.8592G>C), amongst the CRC cases which were not observed in 524 healthy controls. p.R286X localizes to the N-terminal of the TGF-β1 prodomain truncating the protein prior to the active domain. p.W325C and p.C373S mutations are predicted from protein homology modelling with BMP2 to impact deleteriously on BMP4 function. Segregation of p.C373S with adenoma and hyperplastic polyp in first-degree relatives of the case suggests germline mutations may confer a juvenile polyposis-type phenotype. These findings suggest mutation of BMP4is a cause of CRC and the value of protein-based modelling in the elucidation of rare disease-causing variants., (© 2010 Wiley-Liss, Inc.)

Published
2011
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34. Inherited genetic susceptibility to monoclonal B-cell lymphocytosis.

Author

Crowther-Swanepoel D, Corre T, Lloyd A, Gaidano G, Olver B, Bennett FL, Doughty C, Toniolo D, Caligaris-Cappio F, Ghia P, Rossi D, Rawstron AC, Catovsky D, and Houlston RS

Subjects
Aged, Case-Control Studies, Female, Genotype, Humans, Lymphocytosis pathology, Male, B-Lymphocytes pathology, Chromosome Aberrations, Chromosomes, Human genetics, Genetic Predisposition to Disease, Lymphocytosis genetics, Polymorphism, Single Nucleotide genetics
Abstract

Monoclonal B-cell lymphocytosis (MBL) is detectable in > 3% of the general population. Recent data are compatible, at least in a proportion of cases, with MBL being a progenitor lesion for chronic lymphocytic leukemia (CLL) and a surrogate for inherited predisposition. Common single nucleotide polymorphisms (SNPs) at 2q13 (rs17483466), 2q37.1 (rs13397985), 2q37.3 (rs757978), 6p25.3 (rs872071), 8q24.21 (rs2456449), 11q24.1 (rs735665), 15q21.3 (rs7169431), 15q23 (rs7176508), 16q24.1 (rs305061), and 19q13.32 (rs11083846) have been shown to confer a modest but significant increase in CLL risk. To examine the impact of these 10 SNPs on MBL, we analyzed 3 case-control series totaling 419 cases and 1753 controls. An association between genotype and MBL risk was seen for 9 SNPs, 6 of which were statistically significant: rs17483466 (odds ratio [OR] =1.27; P = .02), rs13397985 (OR = 1.40; P = 1.72 × 10(-3)), rs757978 (OR = 1.38; P = .02), rs872071 (OR = 1.27; P = 7.75 × 10(-3)), rs2456449 (OR = 1.31; P = 3.14 × 10(-3)), and rs735665 (OR = 1.63; P = 6.86 × 10(-6)). Collectively, these data provide support for genetic variation influencing CLL risk through predisposition to MBL.

Published
2010
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35. A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3).

Author

Enciso-Mora V, Broderick P, Ma Y, Jarrett RF, Hjalgrim H, Hemminki K, van den Berg A, Olver B, Lloyd A, Dobbins SE, Lightfoot T, van Leeuwen FE, Försti A, Diepstra A, Broeks A, Vijayakrishnan J, Shield L, Lake A, Montgomery D, Roman E, Engert A, von Strandmann EP, Reiners KS, Nolte IM, Smedby KE, Adami HO, Russell NS, Glimelius B, Hamilton-Dutoit S, de Bruin M, Ryder LP, Molin D, Sorensen KM, Chang ET, Taylor M, Cooke R, Hofstra R, Westers H, van Wezel T, van Eijk R, Ashworth A, Rostgaard K, Melbye M, Swerdlow AJ, and Houlston RS

Subjects
Adult, Chromosomes, Human, Pair 10 genetics, Chromosomes, Human, Pair 2 genetics, Chromosomes, Human, Pair 8 genetics, Female, Genome, Human genetics, Humans, Male, Polymorphism, Single Nucleotide genetics, Recombination, Genetic, Chromosomes, Human genetics, GATA3 Transcription Factor genetics, Genetic Loci genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Hodgkin Disease genetics, Proto-Oncogene Proteins c-rel genetics
Abstract

To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10(-8)), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10(-13)) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10(-8)). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10(-50)). These data provide new insight into the pathogenesis of cHL.

Published
2010
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36. Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33.

Author

Houlston RS, Cheadle J, Dobbins SE, Tenesa A, Jones AM, Howarth K, Spain SL, Broderick P, Domingo E, Farrington S, Prendergast JG, Pittman AM, Theodoratou E, Smith CG, Olver B, Walther A, Barnetson RA, Churchman M, Jaeger EE, Penegar S, Barclay E, Martin L, Gorman M, Mager R, Johnstone E, Midgley R, Niittymäki I, Tuupanen S, Colley J, Idziaszczyk S, Thomas HJ, Lucassen AM, Evans DG, Maher ER, Maughan T, Dimas A, Dermitzakis E, Cazier JB, Aaltonen LA, Pharoah P, Kerr DJ, Carvajal-Carmona LG, Campbell H, Dunlop MG, and Tomlinson IP

Subjects
Chromosome Mapping methods, Female, Genotype, Humans, Male, Meta-Analysis as Topic, Odds Ratio, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Risk Assessment, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 12 genetics, Chromosomes, Human, Pair 13 genetics, Chromosomes, Human, Pair 3 genetics, Colorectal Neoplasms genetics, Genetic Predisposition to Disease, Genome-Wide Association Study methods
Abstract

Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10⁻¹⁰ and rs6687758, OR = 1.09, P = 2.27 × 10⁻⁹, 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10⁻⁸), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10⁻¹⁰ and rs7136702, OR = 1.06, P = 4.02 × 10⁻⁸) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10⁻¹⁰). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered., Competing Interests: statement The authors declare no competing financial interests.

Published
2010
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37. Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H.

Author

Pittman AM, Naranjo S, Jalava SE, Twiss P, Ma Y, Olver B, Lloyd A, Vijayakrishnan J, Qureshi M, Broderick P, van Wezel T, Morreau H, Tuupanen S, Aaltonen LA, Alonso ME, Manzanares M, Gavilán A, Visakorpi T, Gómez-Skarmeta JL, and Houlston RS

Subjects
Cell Line, Tumor, Cell Proliferation, Colorectal Neoplasms pathology, Electrophoretic Mobility Shift Assay, Female, Gene Expression Regulation, Neoplastic, Genes, Reporter genetics, Genetic Loci genetics, Humans, Linkage Disequilibrium genetics, Male, Middle Aged, Polymorphism, Single Nucleotide genetics, Protein Binding, Risk Factors, Alleles, Chromosomes, Human, Pair 8 genetics, Colorectal Neoplasms genetics, Eukaryotic Initiation Factor-3 genetics, Genetic Predisposition to Disease, Genetic Variation, Regulatory Sequences, Nucleic Acid genetics
Abstract

Common genetic variation at human 8q23.3 is significantly associated with colorectal cancer (CRC) risk. To elucidate the basis of this association we compared the frequency of common variants at 8q23.3 in 1,964 CRC cases and 2,081 healthy controls. Reporter gene studies showed that the single nucleotide polymorphism rs16888589 acts as an allele-specific transcriptional repressor. Chromosome conformation capture (3C) analysis demonstrated that the genomic region harboring rs16888589 interacts with the promoter of gene for eukaryotic translation initiation factor 3, subunit H (EIF3H). We show that increased expression of EIF3H gene increases CRC growth and invasiveness thereby providing a biological mechanism for the 8q23.3 association. These data provide evidence for a functional basis for the non-coding risk variant rs16888589 at 8q23.3 and provides novel insight into the etiological basis of CRC., Competing Interests: The authors have declared that no competing interests exist.

Published
2010
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38. Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia.

Author

Papaemmanuil E, Hosking FJ, Vijayakrishnan J, Price A, Olver B, Sheridan E, Kinsey SE, Lightfoot T, Roman E, Irving JA, Allan JM, Tomlinson IP, Taylor M, Greaves M, and Houlston RS

Subjects
Alleles, Base Pairing, Base Sequence, CCAAT-Enhancer-Binding Proteins genetics, Case-Control Studies, Child, Child, Preschool, Confidence Intervals, DNA-Binding Proteins genetics, Gene Frequency, Genetic Variation, Genome-Wide Association Study, Genotype, Haplotypes, Humans, Ikaros Transcription Factor genetics, Introns, Linkage Disequilibrium, Meta-Analysis as Topic, Molecular Sequence Data, Odds Ratio, Physical Chromosome Mapping, Polymorphism, Single Nucleotide, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Probability, Recombination, Genetic, Risk Factors, Transcription Factors genetics, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 7, Genetic Predisposition to Disease, Precursor Cell Lymphoblastic Leukemia-Lymphoma etiology
Abstract

To identify risk variants for childhood acute lymphoblastic leukemia (ALL), we conducted a genome-wide association study of two case-control series, analyzing the genotypes with respect to 291,423 tagging SNPs in a total of 907 ALL cases and 2,398 controls. We identified risk loci for ALL at 7p12.2 (IKZF1, rs4132601, odds ratio (OR) = 1.69, P = 1.20 x 10(-19)), 10q21.2 (ARID5B, rs7089424, OR = 1.65, P = 6.69 x 10(-19)) and 14q11.2 (CEBPE, rs2239633, OR = 1.34, P = 2.88 x 10(-7)). The 10q21.2 (ARID5B) risk association appears to be selective for the subset of B-cell precursor ALL with hyperdiploidy. These data show that common low-penetrance susceptibility alleles contribute to the risk of developing childhood ALL and provide new insight into disease causation of this specific hematological cancer. Notably, all three risk variants map to genes involved in transcriptional regulation and differentiation of B-cell progenitors.

Published
2009
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39. Coordination of genetic, epigenetic, and environmental factors in lung development, injury, and repair.

Author

Warburton D and Olver BE

Subjects
Animals, Gene Expression Regulation, Gene Expression Regulation, Developmental, Growth Substances physiology, Homeodomain Proteins physiology, Humans, Nuclear Proteins physiology, Pulmonary Surfactants physiology, Regeneration genetics, Regeneration physiology, Thyroid Nuclear Factor 1, Transcription Factors physiology, Transcription, Genetic, Lung embryology, Lung physiology, Respiratory Distress Syndrome physiopathology
Published
1997
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