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985 results on '"Peters, W.H.M."'

2. Genetic polymorphisms in biotranstormation enzymes in Crohn's disease: association with microsomal epoxide hydrolase. (Inflammatory Bowel Disease)

Author

Jong, D.J. de, Logt, E.M.J. van der, Schaik, A. van, Roelofs, H.M.J., Peters, W.H.M., and Naber, T.H.J.

Subjects
Gene mutations -- Health aspects -- Genetic aspects, Crohn's disease -- Genetic aspects, Health, Genetic aspects, Health aspects
Abstract

Background: Mucosal biotransformation enzymes can modify toxic compounds in the gut. As chemical or oxidative stress may be involved in the aetiology of Crohn's disease, genes encoding for enzymes involved [...]

Published
2003

3. Influence of clinical factors, diet, and drugs on the human upper gastrointestinal glutathione system. (Cancer)

Author

Hoensch, H., Morgenstern, I., Petereit, G., Siepmann, M., Peters, W.H.M., Roelofs, H.M.J., and Kirch, W.

Subjects
Gastrointestinal system -- Physiological aspects, Glutathione metabolism -- Physiological aspects, Health, Physiological aspects
Abstract

Background: Glutathione (GSH) and the cytosolic glutathione S-transferases (GSTs) protect the gastrointestinal mucosa against the toxic effects of a wide variety of compounds, such as reactive oxygen species and electrophiles. [...]

Published
2002

5. Shared heritability and functional enrichment across six solid cancers (vol 10, 431, 2019)

Author

Jiang, X., Finucane, H.K., Schumacher, F.R., Schmit, S.L., Tyrer, J.P., Han, Y., Michailidou, K., Lesseur, C., Kuchenbaecker, K.B., Dennis, J., Conti, D.V., Casey, G., Gaudet, M.M., Huyghe, J.R., Albanes, D., Aldrich, M.C., Andrew, A.S., Andrulis, I.L., Anton-Culver, H., Antoniou, A.C., Antonenkova, N.N., Arnold, S.M., Aronson, K.J., Arun, B.K., Bandera, E.V., Barkardottir, R.B., Barnes, D.R., Batra, J., Beckmann, M.W., Benitez, J., Benlloch, S., Berchuck, A., Berndt, S.I., Bickeboller, H., Bien, S.A., Blomqvist, C., Boccia, S., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Brauch, H., Brenner, H., Brenton, J.D., Brook, M.N., Brunet, J., Brunnstrom, H., Buchanan, D.D., Burwinkel, B., Butzow, R., Cadoni, G., Caldes, T., Caligo, M.A., Campbell, I., Campbell, P.T., Cancel-Tassin, G., Cannon-Albright, L., Campa, D., Caporaso, N., Carvalho, A.L., Chan, A.T., Chang-Claude, J., Chanock, S.J., Chen, C., Christiani, D.C., Claes, K.B.M., Claessens, F., Clements, J., Collee, J.M., Correa, M.C., Couch, F.J., Cox, A., Cunningham, J.M., Cybulski, C., Czene, K., Daly, M.B., deFazio, A., Devilee, P., Diez, O., Gago-Dominguez, M., Donovan, J.L., Dork, T., Duell, E.J., Dunning, A.M., Dwek, M., Eccles, D.M., Edlund, C.K., Edwards, D.R.V., Ellberg, C., Evans, D.G., Fasching, P.A., Ferris, R.L., Liloglou, T., Figueiredo, J.C., Fletcher, O., Fortner, R.T., Fostira, F., Franceschi, S., Friedman, E., Gallinger, S.J., Ganz, P.A., Garber, J., Garcia-Saenz, J.A., Gayther, S.A., Giles, G.G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., Goode, E.L., Goodman, M.T., Goodman, G., Grankvist, K., Greene, M.H., Gronberg, H., Gronwald, J., Guenel, P., Hakansson, N., Hall, P., Hamann, U., Hamdy, F.C., Hamilton, R.J., Hampe, J., Haugen, A., Heitz, F., Herrero, R., Hillemanns, P., Hoffmeister, M., Hogdall, E., Hong, Y.C., Hopper, J.L., Houlston, R., Hulick, P.J., Hunter, D.J., Huntsman, D.G., Idos, G., Imyanitov, E.N., Ingles, S.A., Isaacs, C., Jakubowska, A., James, P., Jenkins, M.A., Johansson, M., John, E.M., Joshi, A.D., Kaneva, R., Karlan, B.Y., Kelemen, L.E., Kuhl, T., Khaw, K.T., Khusnutdinova, E., Kibel, A.S., Kiemeney, L.A., Kim, J., Kjaer, S.K., Knight, J.A., Kogevinas, M., Kote-Jarai, Z., Koutros, S., Kristensen, V.N., Kupryjanczyk, J., Lacko, M., Lam, S., Lambrechts, D., Landi, M.T., Lazarus, P., N.D. le, Lee, E., Lejbkowicz, F., Lenz, H.J., Leslie, G., Lessel, D., Lester, J., Levine, D.A., Li, L., Li, C.I., Lindblom, A., Lindor, N.M., Liu, G., Loupakis, F., Lubinski, J., Maehle, L., Maier, C., Mannermaa, A., Marchand, L., Margolin, S., May, T., McGuffog, L., Meindl, A., Middha, P., Miller, A., Milne, R.L., MacInnis, R.J., Modugno, F., Montagna, M., Moreno, V., Moysich, K.B., Mucci, L., Muir, K., Mulligan, A.M., Nathanson, K.L., Neal, D.E., Ness, A.R., Neuhausen, S.L., Nevanlinna, H., Newcomb, P.A., Newcomb, L.F., Nielsen, F.C., Nikitina-Zake, L., Nordestgaard, B.G., Nussbaum, R.L., Offit, K., Olah, E., Olama, A.A. al, Olopade, O.I., Olshan, A.F., Olsson, H., Osorio, A., Pandha, H., Park, J.Y., Pashayan, N., Parsons, M.T., Pejovic, T., Penney, K.L., Peters, W.H.M., Phelan, C.M., Phipps, A.I., Plaseska-Karanfilska, D., Pring, M., Prokofyeva, D., Radice, P., Stefansson, K., Ramus, S.J., Raskin, L., Rennert, G., Rennert, H.S., Rensburg, E.J., Riggan, M.J., Risch, H.A., Risch, A., Roobol, M.J., Rosenstein, B.S., Rossing, M.A., Ruyck, K., Saloustros, E., Sandler, D.P., Sawyer, E.J., Schabath, M.B., Schleutker, J., Schmidt, M.K., Setiawan, V.W., Shen, H.B., Siegel, E.M., Sieh, W., Singer, C.F., Slattery, M.L., Sorensen, K.D., Southey, M.C., Spurdle, A.B., Stanford, J.L., Stevens, V.L., Stintzing, S., Stone, J., Sundfeldt, K., Sutphen, R., Swerdlow, A.J., Tajara, E.H., Tangen, C.M., Tardon, A., Taylor, J.A., Teare, M.D., Teixeira, M.R., Terry, M.B., Terry, K.L., Thibodeau, S.N., Thomassen, M., Bjorge, L., Tischkowitz, M., Toland, A.E., Torres, D., Townsend, P.A., Travis, R.C., Tung, N., and Tworoger

Published
2019

6. Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers

Author

Kachuri, L. Saarela, O. Bojesen, S.E. Davey Smith, G. Liu, G. Landi, M.T. Caporaso, N.E. Christiani, D.C. Johansson, M. Panico, S. Overvad, K. Trichopoulou, A. Vineis, P. Scelo, G. Zaridze, D. Wu, X. Albanes, D. Diergaarde, B. Lagiou, P. Macfarlane, G.J. Aldrich, M.C. Tardón, A. Rennert, G. Olshan, A.F. Weissler, M.C. Chen, C. Goodman, G.E. Doherty, J.A. Ness, A.R. Bickeböller, H. Wichmann, H.-E. Risch, A. Field, J.K. Teare, M.D. Kiemeney, L.A. Van Der Heijden, E.H.F.M. Carroll, J.C. Haugen, A. Zienolddiny, S. Skaug, V. Wünsch-Filho, V. Tajara, E.H. Ayoub Moysés, R. Daumas Nunes, F. Lam, S. Eluf-Neto, J. Lacko, M. Peters, W.H.M. Le Marchand, L. Duell, E.J. Andrew, A.S. Franceschi, S. Schabath, M.B. Manjer, J. Arnold, S. Lazarus, P. Mukeriya, A. Swiatkowska, B. Janout, V. Holcatova, I. Stojsic, J. Mates, D. Lissowska, J. Boccia, S. Lesseur, C. Zong, X. McKay, J.D. Brennan, P. Amos, C.I. Hung, R.J.

Abstract

Background: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. Methods: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. Results: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 × 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. Conclusions: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci. © 2018 The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Published
2019

9. No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study

Author

Dong, J., Gharahkhani, P., Chow, W.H., Gammon, M.D., Liu, G., Caldas, C., Wu, A.H., Ye, W., Onstad, L., Anderson, L.A., Bernstein, L., Pharoah, P.D., Risch, H.A., Corley, D.A., Fitzgerald, R.C., Iyer, P.G., Reid, B.J., Lagergren, J., Shaheen, N.J., Vaughan, T.L., MacGregor, S., Love, S., Palles, C., Tomlinson, I., Gockel, I., May, A., Gerges, C., Anders, M., Bohmer, A.C., Becker, J., Kreuser, N., Thieme, R., Noder, T., Venerito, M., Veits, L., Schmidt, T., Schmidt, C., Izbicki, J.R., Holscher, A.H., Lang, H., Lorenz, D., Schumacher, B., Mayershofer, R., Vashist, Y., Ott, K., Vieth, M., Weismuller, J., Nothen, M.M., Moebus, S., Knapp, M., Peters, W.H.M., Neuhaus, H., Rosch, T., Ell, C., Jankowski, J., Schumacher, J., Neale, R.E., Whiteman, D.C., Thrift, A.P., Dong, J., Gharahkhani, P., Chow, W.H., Gammon, M.D., Liu, G., Caldas, C., Wu, A.H., Ye, W., Onstad, L., Anderson, L.A., Bernstein, L., Pharoah, P.D., Risch, H.A., Corley, D.A., Fitzgerald, R.C., Iyer, P.G., Reid, B.J., Lagergren, J., Shaheen, N.J., Vaughan, T.L., MacGregor, S., Love, S., Palles, C., Tomlinson, I., Gockel, I., May, A., Gerges, C., Anders, M., Bohmer, A.C., Becker, J., Kreuser, N., Thieme, R., Noder, T., Venerito, M., Veits, L., Schmidt, T., Schmidt, C., Izbicki, J.R., Holscher, A.H., Lang, H., Lorenz, D., Schumacher, B., Mayershofer, R., Vashist, Y., Ott, K., Vieth, M., Weismuller, J., Nothen, M.M., Moebus, S., Knapp, M., Peters, W.H.M., Neuhaus, H., Rosch, T., Ell, C., Jankowski, J., Schumacher, J., Neale, R.E., Whiteman, D.C., and Thrift, A.P.

Abstract

Contains fulltext : 215282.pdf (publisher's version ) (Closed access), BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. RESULTS: Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P = .41). The odds ratio for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P = .18). CONCLUSIONS: In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.

Published
2019

10. Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers

Author

Kachuri, L., Saarela, O., Bojesen, S.E., Smith, G., Liu, G., Landi, M.T., Caporaso, N.E., Christiani, D.C., Johansson, M., Panico, S., Overvad, K., Trichopoulou, A., Vineis, P., Scelo, G., Zaridze, D., Wu, X., Albanes, D., Diergaarde, B., Lagiou, P., Macfarlane, G.J., Aldrich, M.C., Tardon, A., Rennert, G., Olshan, A.F., Weissler, M.C., Chen, C, Goodman, G.E., Doherty, J.A., Ness, A.R., Bickeboller, H., Wichmann, H.E., Risch, A., Field, J.K., Teare, M.D., Kiemeney, L.A.L.M., Heijden, E. van der, Carroll, J.C., Haugen, A., Zienolddiny, S., Skaug, V., Wunsch-Filho, V., Tajara, E.H., Moyses, R. Ayoub, Nunes, F. Daumas, Lam, S., Eluf-Neto, J., Lacko, M., Peters, W.H.M., Marchand, L. Le, Duell, E.J., Andrew, A.S., Franceschi, S., Schabath, M.B., Manjer, J., Arnold, S, Lazarus, P., Mukeriya, A., Swiatkowska, B., Janout, V., Holcatova, I., Stojsic, J., Mates, D., Lissowska, J., Boccia, S., Lesseur, C., Zong, X., McKay, J.D., Brennan, P., Amos, C.I., Hung, R.J., Kachuri, L., Saarela, O., Bojesen, S.E., Smith, G., Liu, G., Landi, M.T., Caporaso, N.E., Christiani, D.C., Johansson, M., Panico, S., Overvad, K., Trichopoulou, A., Vineis, P., Scelo, G., Zaridze, D., Wu, X., Albanes, D., Diergaarde, B., Lagiou, P., Macfarlane, G.J., Aldrich, M.C., Tardon, A., Rennert, G., Olshan, A.F., Weissler, M.C., Chen, C, Goodman, G.E., Doherty, J.A., Ness, A.R., Bickeboller, H., Wichmann, H.E., Risch, A., Field, J.K., Teare, M.D., Kiemeney, L.A.L.M., Heijden, E. van der, Carroll, J.C., Haugen, A., Zienolddiny, S., Skaug, V., Wunsch-Filho, V., Tajara, E.H., Moyses, R. Ayoub, Nunes, F. Daumas, Lam, S., Eluf-Neto, J., Lacko, M., Peters, W.H.M., Marchand, L. Le, Duell, E.J., Andrew, A.S., Franceschi, S., Schabath, M.B., Manjer, J., Arnold, S, Lazarus, P., Mukeriya, A., Swiatkowska, B., Janout, V., Holcatova, I., Stojsic, J., Mates, D., Lissowska, J., Boccia, S., Lesseur, C., Zong, X., McKay, J.D., Brennan, P., Amos, C.I., and Hung, R.J.

Abstract

Contains fulltext : 208363.pdf (publisher's version ) (Closed access), BACKGROUND: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. METHODS: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. RESULTS: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 x 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. CONCLUSIONS: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci.

Published
2019

11. Shared heritability and functional enrichment across six solid cancers.

Author

Fletcher O., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tangen C.M., Fletcher O., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., and Tangen C.M.

Abstract

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 x 10-8), breast and ovarian cancer (rg = 0.24, p = 7 x 10-5), breast and lung cancer (rg = 0.18, p =1.5 x 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 x 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Copyright © 2019, The Author(s).

Published
2019

12. Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature Communications, (2019), 10, 1, (431), 10.1038/s41467-018-08054-4).

Author

Tangen C.M., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fletcher O., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., Wu A.H., Tangen C.M., Wu X., Yannoukakos D., Zheng W., Zienolddiny S., Ziogas A., Zorn K.K., Lane J.M., Saxena R., Thomas D., Hung R.J., Diergaarde B., McKay J., Peters U., Hsu L., Garcia-Closas M., Eeles R.A., Chenevix-Trench G., Brennan P.J., Haiman C.A., Simard J., Easton D.F., Gruber S.B., Pharoah P.D.P., Price A.L., Pasaniuc B., Amos C.I., Kraft P., Lindstrom S., Chen C., Jiang X., Finucane H.K., Schumacher F.R., Schmit S.L., Tyrer J.P., Han Y., Michailidou K., Lesseur C., Kuchenbaecker K.B., Dennis J., Conti D.V., Casey G., Gaudet M.M., Huyghe J.R., Albanes D., Aldrich M.C., Andrew A.S., Andrulis I.L., Anton-Culver H., Antoniou A.C., Antonenkova N.N., Arnold S.M., Aronson K.J., Arun B.K., Bandera E.V., Barkardottir R.B., Barnes D.R., Batra J., Beckmann M.W., Benitez J., Benlloch S., Berchuck A., Berndt S.I., Bickeboller H., Bien S.A., Blomqvist C., Boccia S., Bogdanova N.V., Bojesen S.E., Bolla M.K., Brauch H., Brenner H., Brenton J.D., Brook M.N., Brunet J., Brunnstrom H., Buchanan D.D., Burwinkel B., Butzow R., Cadoni G., Caldes T., Caligo M.A., Campbell I., Campbell P.T., Cancel-Tassin G., Cannon-Albright L., Campa D., Caporaso N., Carvalho A.L., Chan A.T., Chang-Claude J., Chanock S.J., Christiani D.C., Claes K.B.M., Claessens F., Clements J., Collee J.M., Correa M.C., Couch F.J., Cox A., Cunningham J.M., Cybulski C., Czene K., Daly M.B., deFazio A., Devilee P., Diez O., Gago-Dominguez M., Donovan J.L., Dork T., Duell E.J., Dunning A.M., Dwek M., Eccles D.M., Edlund C.K., Edwards D.R.V., Ellberg C., Evans D.G., Fasching P.A., Ferris R.L., Liloglou T., Figueiredo J.C., Fletcher O., Fortner R.T., Fostira F., Franceschi S., Friedman E., Gallinger S.J., Ganz P.A., Garber J., Garcia-Saenz J.A., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Goldgar D.E., Goode E.L., Goodman M.T., Goodman G., Grankvist K., Greene M.H., Gronberg H., Gronwald J., Guenel P., Hakansson N., Hall P., Hamann U., Hamdy F.C., Hamilton R.J., Hampe J., Haugen A., Heitz F., Herrero R., Hillemanns P., Hoffmeister M., Hogdall E., Hong Y.-C., Hopper J.L., Houlston R., Hulick P.J., Hunter D.J., Huntsman D.G., Idos G., Imyanitov E.N., Ingles S.A., Isaacs C., Jakubowska A., James P., Jenkins M.A., Johansson M., John E.M., Joshi A.D., Kaneva R., Karlan B.Y., Kelemen L.E., Kuhl T., Khaw K.-T., Khusnutdinova E., Kibel A.S., Kiemeney L.A., Kim J., Kjaer S.K., Knight J.A., Kogevinas M., Kote-Jarai Z., Koutros S., Kristensen V.N., Kupryjanczyk J., Lacko M., Lam S., Lambrechts D., Landi M.T., Lazarus P., Le N.D., Lee E., Lejbkowicz F., Lenz H.-J., Leslie G., Lessel D., Lester J., Levine D.A., Li L., Li C.I., Lindblom A., Lindor N.M., Liu G., Loupakis F., Lubinski J., Maehle L., Maier C., Mannermaa A., Marchand L.L., Margolin S., May T., McGuffog L., Meindl A., Middha P., Miller A., Milne R.L., MacInnis R.J., Modugno F., Montagna M., Moreno V., Moysich K.B., Mucci L., Muir K., Mulligan A.M., Nathanson K.L., Neal D.E., Ness A.R., Neuhausen S.L., Nevanlinna H., Newcomb P.A., Newcomb L.F., Nielsen F.C., Nikitina-Zake L., Nordestgaard B.G., Nussbaum R.L., Offit K., Olah E., Olama A.A.A., Olopade O.I., Olshan A.F., Olsson H., Osorio A., Pandha H., Park J.Y., Pashayan N., Parsons M.T., Pejovic T., Penney K.L., Peters W.H.M., Phelan C.M., Phipps A.I., Plaseska-Karanfilska D., Pring M., Prokofyeva D., Radice P., Stefansson K., Ramus S.J., Raskin L., Rennert G., Rennert H.S., van Rensburg E.J., Riggan M.J., Risch H.A., Risch A., Roobol M.J., Rosenstein B.S., Rossing M.A., De Ruyck K., Saloustros E., Sandler D.P., Sawyer E.J., Schabath M.B., Schleutker J., Schmidt M.K., Setiawan V.W., Shen H., Siegel E.M., Sieh W., Singer C.F., Slattery M.L., Sorensen K.D., Southey M.C., Spurdle A.B., Stanford J.L., Stevens V.L., Stintzing S., Stone J., Sundfeldt K., Sutphen R., Swerdlow A.J., Tajara E.H., Tardon A., Taylor J.A., Teare M.D., Teixeira M.R., Terry M.B., Terry K.L., Thibodeau S.N., Thomassen M., Bjorge L., Tischkowitz M., Toland A.E., Torres D., Townsend P.A., Travis R.C., Tung N., Tworoger S.S., Ulrich C.M., Usmani N., Vachon C.M., Van Nieuwenhuysen E., Vega A., Aguado-Barrera M.E., Wang Q., Webb P.M., Weinberg C.R., Weinstein S., Weissler M.C., Weitzel J.N., West C.M.L., White E., Whittemore A.S., Wichmann H.-E., Wiklund F., Winqvist R., Wolk A., Woll P., Woods M., and Wu A.H.

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.Copyright © 2019, The Author(s).

Published
2019

13. Erratum: Publisher Correction: Shared heritability and functional enrichment across six solid cancers (Nature communications (2019) 10 1 (431))

Author

Jiang, X. (Xia), Finucane, H.K. (Hilary K.), Schumacher, F.R. (Fredrick R), Schmit, S.L. (Stephanie L.), Tyrer, J.P. (Jonathan P.), Han, Y. (Younghun), Michailidou, K. (Kyriaki), Lesseur, C. (Corina), Kuchenbaecker, K.B. (Karoline), Dennis, J. (Joe), Conti, G. (Giario), Casey, G. (Graham), Gaudet, M.M. (Mia M.), Huyghe, J.R. (Jeroen R.), Albanes, D. (Demetrius), Aldrich, M.C. (Melinda), Andrew, A.S. (Angeline S.), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A.C. (Antonis C.), Antonenkova, N.N. (Natalia N.), Arnold, S.M. (Susanne M.), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Bandera, E.V. (Elisa), Barkardottir, R.B. (Rosa B.), Barnes, D. (Daniel), Batra, J. (Jyotsna), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Benlloch, S. (Sara), Berchuck, A. (Andrew), Berndt, S.I. (Sonja), Bickeböller, H. (Heike), Bien, S.A. (Stephanie A.), Blomqvist, C. (Carl), Boccia, S. (Stefania), Bogdanova, N.V. (Natalia V.), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brenton, J.D. (James D.), Brook, R.H., Brunet, J. (Joan), Brunnström, H. (Hans), Buchanan, D.D. (Daniel D.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Cadoni, G. (Gabriella), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Campbell, P.T. (Peter T.), Cancel-Tassin, G. (Géraldine), Cannon-Albright, L.A. (Lisa), Campa, D. (Daniele), Caporaso, N.E. (Neil), Carvalho, A.L. (André L), Chan, A.T. (Andrew T.), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, C. (Chu), Christiani, D.C. (David C.), Claes, K.B.M. (Kathleen B M), Claessens, F. (Frank), Clements, J. (Judith), Collée, J.M. (J Margriet), Correa, M.C. (Marcia Cruz), Couch, F.J. (Fergus), Cox, A. (Angela), Cunningham, J.M. (Julie), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary), DeFazio, A. (Anna), Devilee, P. (Peter), Diez, O. (Orland), Gago-Dominguez, M. (Manuela), Donovan, J.L. (Jenny L.), Dörk, T. (Thilo), Duell, E.J. (Eric), Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D. (Diana), Edlund, C.K. (Christopher), Edwards, D.R.V. (Digna R Velez), Ellberg, C. (Carolina), Evans, D.G. (D Gareth), Fasching, P.A. (Peter), Ferris, R.L. (Robert L.), Liloglou, T. (Triantafillos), Figueiredo, J.C. (Jane C.), Fletcher, O. (Olivia), Fortner, R.T. (Renée T), Fostira, F. (Florentia), Franceschi, S. (Silvia), Friedman, E. (Eitan), Gallinger, S. (Steve), Ganz, P.A. (Patricia), Garber, J. (Judy), García-Sáenz, J.A. (José A), Gayther, S.A. (Simon), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D.E. (David E.), Goode, E.L. (Ellen), Goodman, M.T. (Marc), Goodman, G. (Gary), Grankvist, K. (Kjell), Greene, M.H. (Mark H.), Grönberg, H. (Henrik), Gronwald, J. (Jacek), Guénel, P. (Pascal), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hamdy, F. (Freddie), Hamilton, R.J. (Robert J.), Hampe, J. (Jochen), Haugen, A. (Aage), Heitz, F. (Florian), Herrero, R. (Rolando), Hillemanns, P. (Peter), Hoffmeister, M. (Michael), Høgdall, E. (Estrid), Hong, Y.-C. (Yun-Chul), Hopper, J.L. (John), Houlston, R. (Richard), Hulick, P.J. (Peter J.), Hunter, D.J. (David), Huntsman, D.G. (David G.), Idos, G. (Gregory), Imyanitov, E.N. (Evgeny), Ingles, S.A. (Sue), Isaacs, C. (Claudine), Jakubowska, A. (Anna), James, M. (Margaret), Jenkins, M.A. (Mark A.), Johansson, M. (Mattias), Johansson, M. (Mikael), John, E.M. (Esther), Joshi, A.D. (Amit D.), Kaneva, R. (Radka), Karlan, B.Y. (Beth), Kelemen, L.E. (Linda E.), Kühl, T. (Tabea), Khaw, K.-T. (Kay-Tee), Khusnutdinova, E.K. (Elza), Kibel, A. (Adam), Kiemeney, L.A. (Lambertus A.), Kim, J. (Jongoh), Kjaer, M. (Michael), Knight, J.A. (Julia), Kogevinas, M. (Manolis), Kote-Jarai, Z., Koutros, S. (Stella), Kristensen, V. (Vessela), Kupryjanczyk, J. (Jolanta), Lacko, M. (Martin), Lam, S. (Stephan), Lambrechts, D. (Diether), Landi, M.T. (Maria Teresa), Lazarus, P. (Philip), Le, N.D. (Nhu D.), Lee, E. 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(Erin M.), Sieh, W. (Weiva), Singer, C.F. (Christian), Slattery, M.L. (Martha L.), Sorensen, K.D. (Karina Dalsgaard), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stanford, J.L. (Janet L.), Stevens, V.L. (Victoria L.), Stintzing, S. (Sebastian), Stone, J. (Jennifer), Sundfeldt, K. (Karin), Sutphen, R. (Rebecca), Swerdlow, A.J. (Anthony ), Tajara, E.H. (Eloiza H.), Tangen, C.M. (Catherine M.), Tardón, A. (Adonina), Taylor, J.A. (Jack A.), Teare, M.D. (M Dawn), Teixeira, P.J., Terry, M.B. (Mary Beth), Terry, K.L. (Kathryn L.), Thibodeau, S.N. (Stephen), Thomassen, M. (Mads), Bjørge, L. (Line), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Townsend, P.A. (Paul A.), Travis, S.P.L. (Simon), Tung, N. (Nadine), Tworoger, S. (Shelley), Ulrich, C. (Cornelia), Usmani, N. (Nawaid), Vachon, C. (Celine), Van Nieuwenhuysen, E. (Els), Vega, A. (Ana), Aguado-Barrera, M.E. (Miguel Elías), Wang, Q. (Qin), Webb, P. (Penny), Weinberg, C.R. (Clarice R.), Weinstein, S. (Stephanie), Weissler, M.C. (Mark C.), Weitzel, J.N. (Jeffrey), West, C.M.L. (Catharine M L), White, E. (Emily), Whittemore, A.S. (Alice), Wichmann, H.-E. (H-Erich), Wiklund, F. (Fredrik), Winqvist, R. (Robert), Wolk, K. (Kerstin), Woll, P.J. (Penella J), Woods, M.O. (Michael), Wu, A.H. (Anna H.), Wu, X. (Xifeng), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zienolddiny, S. (Shanbeh), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Lane, J.M. (Jacqueline M.), Saxena, R. (Richa), Thomas, D.C. (Duncan), Hung, R.J. (Rayjean J.), Diergaarde, B. (Brenda), McKay, J. (James), Peters, U. (Ulrike), Hsu, L. (Li), García-Closas, M. (Montserrat), Eeles, R.A. (Rosalind A.), Chenevix-Trench, G. (Georgia), Brennan, P.J. (Paul J.), Haiman, C.A. (Christopher), Simard, J. (Jacques), Easton, D.F. (Douglas), Gruber, S.B. (Stephen), Pharoah, P.D.P. (Paul), Price, A.L. (Alkes L.), Pasaniuc, B. (Bogdan), Amos, C.I. (Christopher I.), Kraft, P. (Peter), Lindström, S. (Sara), Jiang, X. (Xia), Finucane, H.K. (Hilary K.), Schumacher, F.R. (Fredrick R), Schmit, S.L. (Stephanie L.), Tyrer, J.P. (Jonathan P.), Han, Y. (Younghun), Michailidou, K. (Kyriaki), Lesseur, C. (Corina), Kuchenbaecker, K.B. (Karoline), Dennis, J. (Joe), Conti, G. (Giario), Casey, G. (Graham), Gaudet, M.M. (Mia M.), Huyghe, J.R. (Jeroen R.), Albanes, D. (Demetrius), Aldrich, M.C. (Melinda), Andrew, A.S. (Angeline S.), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Antoniou, A.C. (Antonis C.), Antonenkova, N.N. (Natalia N.), Arnold, S.M. (Susanne M.), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Bandera, E.V. (Elisa), Barkardottir, R.B. (Rosa B.), Barnes, D. (Daniel), Batra, J. (Jyotsna), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Benlloch, S. (Sara), Berchuck, A. (Andrew), Berndt, S.I. (Sonja), Bickeböller, H. (Heike), Bien, S.A. (Stephanie A.), Blomqvist, C. (Carl), Boccia, S. (Stefania), Bogdanova, N.V. (Natalia V.), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brenton, J.D. (James D.), Brook, R.H., Brunet, J. (Joan), Brunnström, H. (Hans), Buchanan, D.D. (Daniel D.), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Cadoni, G. (Gabriella), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Campbell, P.T. (Peter T.), Cancel-Tassin, G. (Géraldine), Cannon-Albright, L.A. (Lisa), Campa, D. (Daniele), Caporaso, N.E. (Neil), Carvalho, A.L. (André L), Chan, A.T. (Andrew T.), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, C. (Chu), Christiani, D.C. (David C.), Claes, K.B.M. (Kathleen B M), Claessens, F. (Frank), Clements, J. (Judith), Collée, J.M. (J Margriet), Correa, M.C. (Marcia Cruz), Couch, F.J. (Fergus), Cox, A. (Angela), Cunningham, J.M. (Julie), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary), DeFazio, A. (Anna), Devilee, P. (Peter), Diez, O. (Orland), Gago-Dominguez, M. (Manuela), Donovan, J.L. (Jenny L.), Dörk, T. (Thilo), Duell, E.J. (Eric), Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D. (Diana), Edlund, C.K. (Christopher), Edwards, D.R.V. (Digna R Velez), Ellberg, C. (Carolina), Evans, D.G. (D Gareth), Fasching, P.A. (Peter), Ferris, R.L. (Robert L.), Liloglou, T. (Triantafillos), Figueiredo, J.C. (Jane C.), Fletcher, O. (Olivia), Fortner, R.T. (Renée T), Fostira, F. (Florentia), Franceschi, S. (Silvia), Friedman, E. (Eitan), Gallinger, S. (Steve), Ganz, P.A. (Patricia), Garber, J. (Judy), García-Sáenz, J.A. (José A), Gayther, S.A. (Simon), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D.E. (David E.), Goode, E.L. (Ellen), Goodman, M.T. (Marc), Goodman, G. (Gary), Grankvist, K. (Kjell), Greene, M.H. (Mark H.), Grönberg, H. (Henrik), Gronwald, J. (Jacek), Guénel, P. (Pascal), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hamdy, F. (Freddie), Hamilton, R.J. (Robert J.), Hampe, J. (Jochen), Haugen, A. (Aage), Heitz, F. (Florian), Herrero, R. (Rolando), Hillemanns, P. (Peter), Hoffmeister, M. 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(Heinz-Josef), Leslie, G. (Goska), Lessel, D. (Davor), Lester, J. (Jenny), Levine, D.A. (Douglas), Li, L. (Li), Li, C.I. (Christopher I.), Lindblom, A. (Annika), Lindor, N.M. (Noralane), Liu, G. (Geoffrey), Loupakis, F. (Fotios), Lubinski, J. (Jan), Maehle, L., Maier, C. (Christiane), Mannermaa, A. (Arto), Le Marchand, L. (Loic), Margolin, S. (Sara), May, T. (Taymaa), McGuffog, L. (Lesley), Meindl, A. (Alfons), Middha, P. (Pooja), Miller, A. (Austin), Milne, R.L. (Roger), MacInnis, R.J. (Robert J.), Modugno, F. (Francesmary), Montagna, M. (Marco), Moreno, V. (Víctor), Moysich, K.B. (Kirsten), Mucci, L. (Lorelei), Muir, K. (Kenneth), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neal, D. (David), Ness, A.R. (Andrew R.), Neuhausen, S.L. (Susan L.), Nevanlinna, H. (Heli), Newcomb, P. (Polly), Newcomb, L.F. (Lisa F.), Nielsen, F. (Finn), Nikitina-Zake, L. (Liene), Nordestgaard, B.G. (Børge), Nussbaum, R. (Robert), Offit, K. (Kenneth), Olah, E. (Edith), Olama, A.A.A. (Ali Amin Al), Olopade, O.I. (Olofunmilayo), Olshan, A.F. (Andrew F.), Olsson, H. (Håkan), Osorio, A. (Ana), Pandha, H. (Hardev), Park, J.Y. (Jong Y.), Pashayan, N. (Nora), Parsons, M. (Marilyn), Pejovic, T. (Tanja), Penney, K.L. (Kathryn L.), Peters, W.H.M. (Wilbert), Phelan, C. (Catherine), Phipps, A.I. (Amanda I.), Plaseska-Karanfilska, D. (Dijana), Pring, M. (Miranda), Prokofyeva, D. (Darya), Radice, P. (Paolo), Stefansson, K. (Kari), Ramus, S.J. (Susan), Raskin, L. (Leon), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Rensburg, E.J. (Elizabeth) van, Riggan, M.J. (Marjorie J.), Risch, H.A. (Harvey A.), Risch, A. (Angela), Roobol, M.J. (Monique J.), Rosenstein, B.S. (Barry S.), Rossing, M.A. (Mary Anne), De Ruyck, K. (Kim), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Sawyer, E.J. (Elinor J.), Schabath, M.B. (Matthew), Schleutker, J. (Johanna), Schmidt, M.K. (Marjanka), Setiawan, V.W. (V Wendy), Shen, H. (Hongbing), Siegel, E.M. (Erin M.), Sieh, W. (Weiva), Singer, C.F. (Christian), Slattery, M.L. (Martha L.), Sorensen, K.D. (Karina Dalsgaard), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stanford, J.L. (Janet L.), Stevens, V.L. (Victoria L.), Stintzing, S. (Sebastian), Stone, J. (Jennifer), Sundfeldt, K. (Karin), Sutphen, R. (Rebecca), Swerdlow, A.J. (Anthony ), Tajara, E.H. (Eloiza H.), Tangen, C.M. (Catherine M.), Tardón, A. (Adonina), Taylor, J.A. (Jack A.), Teare, M.D. (M Dawn), Teixeira, P.J., Terry, M.B. (Mary Beth), Terry, K.L. (Kathryn L.), Thibodeau, S.N. (Stephen), Thomassen, M. (Mads), Bjørge, L. (Line), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Townsend, P.A. (Paul A.), Travis, S.P.L. (Simon), Tung, N. (Nadine), Tworoger, S. (Shelley), Ulrich, C. (Cornelia), Usmani, N. (Nawaid), Vachon, C. (Celine), Van Nieuwenhuysen, E. (Els), Vega, A. (Ana), Aguado-Barrera, M.E. (Miguel Elías), Wang, Q. (Qin), Webb, P. (Penny), Weinberg, C.R. (Clarice R.), Weinstein, S. (Stephanie), Weissler, M.C. (Mark C.), Weitzel, J.N. (Jeffrey), West, C.M.L. (Catharine M L), White, E. (Emily), Whittemore, A.S. (Alice), Wichmann, H.-E. (H-Erich), Wiklund, F. (Fredrik), Winqvist, R. (Robert), Wolk, K. (Kerstin), Woll, P.J. (Penella J), Woods, M.O. (Michael), Wu, A.H. (Anna H.), Wu, X. (Xifeng), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zienolddiny, S. (Shanbeh), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Lane, J.M. (Jacqueline M.), Saxena, R. (Richa), Thomas, D.C. (Duncan), Hung, R.J. (Rayjean J.), Diergaarde, B. (Brenda), McKay, J. (James), Peters, U. (Ulrike), Hsu, L. (Li), García-Closas, M. (Montserrat), Eeles, R.A. (Rosalind A.), Chenevix-Trench, G. (Georgia), Brennan, P.J. (Paul J.), Haiman, C.A. (Christopher), Simard, J. (Jacques), Easton, D.F. (Douglas), Gruber, S.B. (Stephen), Pharoah, P.D.P. (Paul), Price, A.L. (Alkes L.), Pasaniuc, B. (Bogdan), Amos, C.I. (Christopher I.), Kraft, P. (Peter), and Lindström, S. (Sara)

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019
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16. Biotransformation enzymes in human intestine: critical low levels in the colon?

Author

Peters, W.H.M., Kock, L., Nagengast, F.M., and Kremers, P.G.

Subjects
Colon (Anatomy) -- Physiological aspects, Digestive enzymes -- Physiological aspects, Gastrointestinal system -- Physiological aspects, Health
Abstract

Biotransformation enzymes are those that catalyze a change in the physical form of ingested non-nutritive substances, usually converting them to an inactive or nontoxic state. A large proportion of the body's biotransformation occurs in the liver, but a significant amount occurs in the small and large intestines during the digestion and absorption of food. Little is known about the localization or molecular nature of the biotransformation enzymes in the gastrointestinal tract. To investigate the distribution and composition of biotransformation enzymes in the small and large intestine, intestinal segments were removed post mortem from formerly healthy kidney donors, and analyzed for the presence and type of three different enzymes: glutathione S-transferase, uridine diphosphate-glucuronosyltransferase, and cytochrome P-450. The activity of each of the three enzymes decreased slightly from the beginning to the end segments of the small intestine; there was a large decrement in activity at the transition from the small to the large intestine. Additionally, the molecular configuration of each of the enzymes was slightly different at different levels of the intestine; once again, the largest differences were seen between the large and small intestines. The low levels of biotransformation enzymes seen in the large intestine of these healthy subjects might be a partial explanation for the higher rates of cancer seen in the large (compared to small) intestine; toxins which escape degradation in the small intestine are less likely to be degraded upon arrival at the large intestine, and are more likely to exert toxic effects. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1991

17. Urinalysis of MMX-mesalazine as a tool to monitor 5-ASA adherence in daily IBD practice

Author

Romkens, T.E.H., Morsche, R.H.M. te, Peters, W.H.M., Burger, D.M., Hoentjen, F., and Drenth, J.P.H.

Subjects
All institutes and research themes of the Radboud University Medical Center, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

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Published
2018

19. Association of BRCA2 K3326* With Small Cell Lung Cancer and Squamous Cell Cancer of the Skin

Author

Rafnar, T., Sigurjonsdottir, G.R., Stacey, S.N., Halldorsson, G., Sulem, P., Pardo, L.M., Helgason, H., Sigurdsson, S.T., Gudjonsson, T., Tryggvadottir, L., Olafsdottir, G.H., Jonasson, J.G., Alexiusdottir, K., Sigurdsson, A., Gudmundsson, J., Saemundsdottir, J., Sigurdsson, J.K., Johannsdottir, H., Uitterlinden, A., Vermeulen, S.H., Galesloot, T.E., Allain, D.C., Lacko, M., Sigurgeirsson, B., Thorisdottir, K., Johannsson, O.T., Sigurdsson, F., Ragnarsson, G.B., Isaksson, H., Hardardottir, H., Gudbjartsson, T., Gudbjartsson, D.F., Masson, G., Kiemeney, B., Toland, A.E., Nijsten, T., Peters, W.H.M., Olafsson, J.H., Jonsson, S., Thorsteinsdottir, U., Thorleifsson, G., Stefansson, K., Rafnar, T., Sigurjonsdottir, G.R., Stacey, S.N., Halldorsson, G., Sulem, P., Pardo, L.M., Helgason, H., Sigurdsson, S.T., Gudjonsson, T., Tryggvadottir, L., Olafsdottir, G.H., Jonasson, J.G., Alexiusdottir, K., Sigurdsson, A., Gudmundsson, J., Saemundsdottir, J., Sigurdsson, J.K., Johannsdottir, H., Uitterlinden, A., Vermeulen, S.H., Galesloot, T.E., Allain, D.C., Lacko, M., Sigurgeirsson, B., Thorisdottir, K., Johannsson, O.T., Sigurdsson, F., Ragnarsson, G.B., Isaksson, H., Hardardottir, H., Gudbjartsson, T., Gudbjartsson, D.F., Masson, G., Kiemeney, B., Toland, A.E., Nijsten, T., Peters, W.H.M., Olafsson, J.H., Jonsson, S., Thorsteinsdottir, U., Thorleifsson, G., and Stefansson, K.

Abstract

Contains fulltext : 195644.pdf (publisher's version ) (Closed access), Background: Most pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity for comprehensive characterization of the cancer risk profiles of K3326* and HBOC mutations because a single mutation, BRCA2 999del5, is responsible for almost all BRCA2-related HBOC in the population. Methods: Genotype information on 43 641 cancer patients and 370 971 control subjects from Iceland, the Netherlands, and the United States was used to assess the cancer risk profiles of K3326* and BRCA2 999del5. BRCA2 expression was assessed using RNAseq data from blood (n = 2233), as well as 52 tissues reported in the GTEx database. Results: The cancer risks associated with K3326* are fundamentally different from those associated with 999del5. We report for the first time an association between K3326* and small cell lung cancer (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.35 to 3.16) and squamous cell carcinoma of the skin (OR = 1.69, 95% CI = 1.26 to 2.26). Individuals homozygous for K3326* reach old age and have children. Unlike BRCA2 999del5, the K3326* allele does not affect the level of BRCA2 transcripts, and the allele is expressed to the same extent as the wild-type allele. Conclusions: K3326* associates primarily with cancers that have strong environmental genotoxic risk factors. Expression of the K3326* allele suggests that a variant protein may be made that retains the DNA repair capabilities important to hormone-responsive tissues but may be less efficient in responding to genotoxic stress.

Published
2018

21. Haptoglobin and its association with the HELLP syndrome. (Letter to JMG)

Author

Raijmakers, M.T.M., Roes, E.M., Morsche, R.H.M. te, Steegers, E.A.P., and Peters, W.H.M.

Subjects
Preeclampsia -- Genetic aspects -- Physiological aspects, HELLP syndrome -- Genetic aspects -- Physiological aspects, Haptoglobin -- Physiological aspects, Health, Physiological aspects, Genetic aspects
Abstract

Haptoglobin (Hp) is an acute phase [α.sub.2]-sialoglycorprotein which is characterised by molecular heterogeneity. (1) Owing to a genetic polymorphism, different Hp phenotypes exist of which Hp1-l, Hp1-2, and Hp2-2 are [...]

Published
2003

22. Genetic polymorphisms in UDP-glucuronosyltransferase 1A6 and 1A7 and the risk for benign Warthin's tumors of the parotid gland

Author

Lacko, M., Voogd, A.C., Goor, R.C. van de, Roelofs, H.M., Morsche, R.H.M. te, Bouvy, N.D., Peters, W.H.M., and Manni, J.J.

Subjects
stomatognathic diseases, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]
Abstract

Contains fulltext : 172620.pdf (Publisher’s version ) (Closed access) BACKGROUND: Warthin's tumors of the parotid gland are associated with smoking, whereas pleomorphic adenomas are not. Genetic polymorphisms in biotransformation enzymes, involved in detoxification of toxins and carcinogens in cigarette smoke, might modify the corresponding enzyme activity and influence detoxifying capacity. We hypothesize that these genetic polymorphisms may influence the individual risk for Warthin's tumor, but not for pleomorphic adenomas. METHODS: Blood from 146 patients with benign parotid gland tumors and 437 controls were investigated for polymorphisms in several biotransformation enzymes. Based on these polymorphisms, patients and controls were divided according to predicted enzyme activity (low, intermediate, and high). RESULTS: Prevalence of predicted intermediate and high activity UGT1A7 and UGT1A6 genotypes was significantly higher in the patients with Warthin's tumors, but not in patients with pleomorphic adenomas, compared with healthy controls. CONCLUSION: Predicted intermediate and high activity UGT1A7 and UGT1A6 genotypes are associated with an increased risk for Warthin's tumor. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E717-E723, 2016.

Published
2016

23. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

Author

Lesseur, C. Diergaarde, B. Olshan, A.F. Wünsch-Filho, V. Ness, A.R. Liu, G. Lacko, M. Eluf-Neto, J. Franceschi, S. Lagiou, P. Macfarlane, G.J. Richiardi, L. Boccia, S. Polesel, J. Kjaerheim, K. Zaridze, D. Johansson, M. Menezes, A.M. Curado, M.P. Robinson, M. Ahrens, W. Canova, C. Znaor, A. Castellsagué, X. Conway, D.I. Holcátová, I. Mates, D. Vilensky, M. Healy, C.M. Szeszenia-Dabrowska, N. Fabiánová, E. Lissowska, J. Grandis, J.R. Weissler, M.C. Tajara, E.H. Nunes, F.D. De Carvalho, M.B. Thomas, S. Hung, R.J. Peters, W.H.M. Herrero, R. Cadoni, G. Bueno-De-Mesquita, H.B. Steffen, A. Agudo, A. Shangina, O. Xiao, X. Gaborieau, V. Chabrier, A. Anantharaman, D. Boffetta, P. Amos, C.I. McKay, J.D. Brennan, P.

Abstract

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10 â'8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci - 9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1∗1301-HLA-DQA1∗0103-HLA-DQB1∗0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers. © 2016 Nature America, Inc. part of Springer Nature, All Rights reserved.

Published
2016

24. Genetic polymorphisms in GSTA1, GSTP1, GSTT1, and GSTM1 and gastric cancer risk in a Vietnamese population

Author

Nguyen Van, T., Janssen, M.J., Oijen, M.G.H. van, Bergevoet, S.M., Morsche, R.H.M. te, Asten, H.A.G.H. van, Laheij, R.J.F., Peters, W.H.M., and Jansen, J.B.M.J.

Subjects
Health aging / healthy living [IGMD 5], Translational research [ONCOL 3], Aetiology, screening and detection [ONCOL 5]
Abstract

Item does not contain fulltext Glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of noxious agents. Genes encoding for GSTA1, GSTP1, GSTT1, and GSTM1 proteins are polymorphic in humans, which can result in (partial) loss of enzyme activity. Previous epidemiologic studies have associated dysfunction of these GST genes with a higher risk of cancer, but this is still controversial. The aim of this study was to investigate the susceptibility to gastric cancer in relation to the above-mentioned GST polymorphisms. Patients visiting the Can Tho General Hospital in Vietnam between January 2004 and August 2004 for upper gastrointestinal endoscopy, who were diagnosed with gastric cancer, were compared with a control group of endoscoped dyspepsia patients with no history of malignancy. Genotypes of the GSTs mentioned above were assessed by multiplex PCR. Fifty-nine patients with gastric cancer (mean age: 63 years, 80% males), and 109 dyspeptic controls (mean age: 46 years, 69% males) were included in this study. The frequencies of the combined heterozygote and homozygote mutant GSTA1 and GSTP1 genotypes were 10% and 48% in patients with gastric cancer versus 28% and 40% in dyspeptic controls, respectively. GSTT1 and GSTM1 were deleted in 42% and 73% of patients with gastric cancer and in 35% and 69% of the controls, respectively. The GSTA1 homozygous wild-type genotype was significantly more often present in patients with gastric cancer compared with controls (odds ratio 4.3, 95% CI 1.2-17), which was even more apparent after adjustment for age, gender, current smoking, current alcohol consumption, and polymorphisms in GSTP1, GSTT1, or GSTM1 (odds ratio 5.0, 95% CI 1.2-25). The present work shows that the homozygous wild-type GSTA1 genotype is associated with gastric cancer in a Vietnamese population, whereas there was no relationship with polymorphisms in GSTP1, GSTT1, or GSTM1.

Published
2010

25. The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid

Author

Clappers, N., Oijen, M.G.H. van, Sundaresan, S., Brouwer, M.A., Morsche, R.H.M. te, Keuper, W., Peters, W.H.M., Drenth, J.P.H., and Verheugt, F.W.A.

Subjects
Cardiovascular diseases [NCEBP 14], Genetic defects of metabolism [UMCN 5.1], Translational research [ONCOL 3], Membrane transport and intracellular motility [NCMLS 5], Aetiology, screening and detection [ONCOL 5], Molecular gastro-enterology and hepatology [IGMD 2], Heart, lung and circulation [UMCN 2.1]
Abstract

Contains fulltext : 70838.pdf (Publisher’s version ) (Closed access) Aspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX-1), thus reducing thromboxane A2 formation and platelet aggregation. The C50T polymorphism of COX-1 is associated with an impaired inhibition of both thromboxane production and in-vitro platelet aggregation by aspirin. We studied whether this polymorphism is also associated with the risk of clinical thrombotic events in patients using aspirin. We included 496 patients admitted to our Coronary Care Unit for various indications treated with aspirin 80 mg daily. Genotyping for the C50T polymorphism demonstrated that 86.7% of the patients had the common genotype, and 13.3% had the variant (12.5% heterozygous, 0.8% homozygous). Baseline variables were well balanced, except that patients with the common genotype more frequently used aspirin prior to admission compared to those patients with the variant genotype. The composite primary endpoint of myocardial infarction, stroke, and/or cardiovascular death occurred in 98 patients (19.8%). Myocardial infarction occurred in 9.6% of patients, stroke in 1.6%, and cardiovascular death in 12.1%. The unadjusted hazard ratio (95% CI) for the primary endpoint for patients with the variant versus the common genotype was 1.07 (0.62-1.85), p = 0.8. The adjusted hazard ratio was 0.86 (0.49-1.50), p = 0.6. In prior laboratory studies the COX-1 C50T polymorphism was associated with an impaired inhibitory effect of aspirin on thromboxane production and platelet function. However, in this cohort of patients using low-dose aspirin for secondary prevention the polymorphism was not associated with a higher risk of atherothrombotic events.

Published
2008

26. Vascular and metabolic effects of the haem oxygenase-1 inducer haem arginate in subjects with the metabolic syndrome: A translational cross-over study.

Author

Dekker, D., Dorresteijn, M.J., Peters, W.H.M., Bilos, A., Pennings, S.W.C., Wagener, F.A.D.T.G., Smits, P., Dekker, D., Dorresteijn, M.J., Peters, W.H.M., Bilos, A., Pennings, S.W.C., Wagener, F.A.D.T.G., and Smits, P.

Abstract

1 januari 2016, Item does not contain fulltext, This translational randomized and vehicle-controlled cross-over study was performed to assess the impact of haem arginate treatment on haem oxygenase-1 induction, endothelial function and insulin sensitivity in subjects with the metabolic syndrome (n = 14). Both treatment periods consisted of 5 days. Haem arginate or vehicle (l-arginine) was administered intravenously on Days 1 and 3. Forearm blood flow in response to acetylcholine and nitroglycerine was measured by venous occlusion plethysmography (Day 3), insulin sensitivity by a hyperinsulinaemic clamp procedure (Day 5). Haem arginate did not improve endothelial function or insulin sensitivity but significantly reduced the vasodilator response to nitroglycerine (p < 0.01). These negative findings are in contrast to the preclinical data, which may be due to short duration of therapy and limited haem oxygenase-1 induction as well as interference by markedly elevated plasma haem levels observed after haem arginate treatment (p < 0.01). Future studies should pay attention to the delicate balance between sufficient dosing and timely normalization of plasma haem levels.

Published
2016

27. Profiling of circulating microRNAs in patients with Barrett's esophagus and esophageal adenocarcinoma

Author

Bus, P., Kestens, C., Kate, F.J. ten, Peters, W.H.M., Drenth, J.P., Roodhart, J.M., Siersema, P.D., Baal, J.W. van, Bus, P., Kestens, C., Kate, F.J. ten, Peters, W.H.M., Drenth, J.P., Roodhart, J.M., Siersema, P.D., and Baal, J.W. van

Abstract

Contains fulltext : 171269.pdf (Publisher’s version ) (Open Access), BACKGROUND: Circulating microRNAs (miRNAs) have been suggested as novel markers for various diseases. The goal of this pilot study was to identify circulating miRNAs differentially expressed comparing Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), and controls. METHODS: MicroRNA expression profiling was performed by qPCR array using plasma from six controls and eight BE and eight EAC patients. Validation was performed by analyzing the expression of six selected miRNAs, by qRT-PCR in 115 plasma samples of controls, BE, and EAC patients. Diagnostic accuracy was evaluated by area under the curve (AUC) analysis. RESULTS: We identified three miRNAs that were elevated in EAC and four miRNAs that were elevated in BE. Further validation showed that miRNA-382-5p was significantly increased and miRNA-133a-3p significantly decreased in EAC. miRNA-194-5p and miRNA-451a were significantly increased and miRNA-136-5p significantly decreased in BE versus controls. A combination of three or more miRNAs was found to have a good diagnostic performance in discriminating BE from controls (AUC: 0.832), EAC from controls (AUC: 0.846), and BE from EAC (AUC: 0.797). CONCLUSION: Our data suggest that circulating miRNAs are differentially expressed in BE and EAC. The miRNAs identified may be used for future non-invasive screening of BE and EAC.

Published
2016

29. Combined polymorphisms in UDP-glucuronosyltransferases 1A1 and 1A6: implications for patients with Gilbert's syndrome

Author

Peters, W.H.M., Morsche, R.H.M. te, and Roelofs, H.M.J.

Subjects
Genetic defects of metabolism [UMCN 5.1]
Abstract

Item does not contain fulltext BACKGROUND/AIMS: UDP-glucuronosyltransferases (UGTs) are important enzymes involved in glucuronidation of various exogenous and endogenous compounds. Studies were undertaken on the variability of three UGT enzyme activities in human livers. Enzyme activities were associated with genetic polymorphisms in UGT1A1 (UGT1A1*28) and UGT1A6 (UGT1A6*2). UGT1A1*28 is associated with Gilbert's syndrome, a deficiency in glucuronidation of bilirubin leading to mild hyperbilirubinemia, whereas UGT1A6*2 may result in low glucuronidation rates of several drugs. METHODS: Enzyme activities and genetic polymorphisms were assessed in 39 human liver samples, and polymorphisms were also assessed in blood of 253 healthy controls. RESULTS: Associations were found between UGT enzyme activities of bilirubin (B) and 4-nitrophenol (NP; r=0.47, P=0.0024), B and 4-methylumbelliferone (MUB; r=0.54, P=0.0003), and NP and MUB (r=0.89, P

Published
2003

30. Glutathione S-transferases P1-1 and A1-1 in ovarian cyst fluids

Author

Boss, E.A., Peters, W.H.M., Roelofs, H.M.J., Boonstra, H., Steegers, E.A.P., Massuger, L.F.A.G., and Obstetrics & Gynecology

Subjects
(Patho)Physiological, endocrinological and methabolic aspects [Prevention of disorders in human reproduction], Metabole aspecten van maag-, darm- en leveraandoeningen, Metabolic aspects of gastrointestinal diseases, (Patho-)fysiologische, endocriene en metabole aspecten. [Preventie van stoornissen in de menselijke voortplanting]
Abstract

Item does not contain fulltext PURPOSE: The purpose of the present study was to determine the gluthathione S-transferases (GST) P1-1 and A1-1 levels in cyst fluid from malignant, borderline, and benign ovarian tumors. The clinical relevance of these enzymes in cyst fluid was investigated, including the possible relation with resistance to chemotherapy. METHODS: A total of 90 ovarian cysts were punctured for cyst fluid collection. GSTP1-1 and GSTA1-1 concentrations were determined by ELISA in cyst fluid from 23 malignant, 9 borderline, and 51 benign primary ovarian tumors, and levels were correlated with histopathological data. RESULTS: Significantly higher GSTP1-I concentrations were found in cyst fluid from malignant (median: 477 ng/ml), compared with benign (median: 52 ng/ml) ovarian cysts (p < 0.0001), as well as in fluid from borderline (median: 366 ng/ml) compared with benign cysts (p < 0.0001). No significant differences were found in cyst fluid GSTA1-1 concentrations between the histologic subgroups. In cyst fluid from malignant tumors higher GSTPI-1 and lower GSTAI-1 concentrations were found in patients with worse prognostic factors: FIGO II-III-IV, grade 2-3, residual tumor > 2 cm, presence of ascites, patients with recurrent disease, and survival, but differences were not significant. In the subgroup of patients that received cisplatin-based chemotherapy (n = 14) significantly higher GSTP1-1 (p = 0.01) concentrations were found in patients with recurrence compared with patients without recurrence. Considering only FIGO stage I patients, a differentiation could be made between patients with or without recurrence based on cyst fluid GSTP I - I concentrations. CONCLUSIONS: Determination of glutathione S-transferases P 1-1 in cyst fluid samples from ovarian tumors can be of additiona] value in the differentiation between histologic subgroups. In case of possible low malignant potential cysts where sampling of the most representative tissue can be an issue, determination of GSTP- I concentrations in cyst fluid may optimise histopathologic classification. Cyst fluid GSTP1-1 seems to be a good marker for aggressiveness of the ovarian tumor, and it may predict response to chemotherapy.

Published
2001

34. Glutathione and glutathione related enzymes in reproduction-a review

Author

Knapen, M.F.C.M., Zusterzeel, P.L.M., Peters, W.H.M., and Steegers, E.A.P.

Subjects
Metabole aspecten van maag-, darm- en leveraandoeningen, The etiological rol of the glutahione- S-transferase system in preeclampsia and the HELLP syndrome, Metabolic aspects of gastrointestinal diseases, Onderzoek naar de rol van het glutathion-S-transferase (GST) systeem in de etiologie van pre-eclampsie en het HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndroom bij zwangeren
Abstract

Item does not contain fulltext

Published
1999

35. Allopurinol and 5-aminosalicylic acid influence thiopurine-induced hepatotoxicity in vitro

Author

Broekman, M.M.T.J., Roelofs, H.M., Wong, D.R., Kerstholt, M., Leijten, A., Hoentjen, F., Peters, W.H.M., Wanten, G.J.A., Jong, D.J. de, Broekman, M.M.T.J., Roelofs, H.M., Wong, D.R., Kerstholt, M., Leijten, A., Hoentjen, F., Peters, W.H.M., Wanten, G.J.A., and Jong, D.J. de

Abstract

Contains fulltext : 153788.pdf (publisher's version ) (Open Access), INTRODUCTION: The use of thiopurines is frequently accompanied by hepatotoxicity. Studies on hepatocyte cultures showed a time- and dose-dependent increase of thiopurine toxicity. 5-Aminosalicylic acid (5-ASA) and allopurinol can influence thiopurine metabolism; however, it is unknown whether this affects in vitro cytotoxicity. METHODS: Human hepatoma cells (Huh7, HepG2 and HepaRG) were incubated with increasing concentrations of thiopurines, 5-ASA or allopurinol. Water-soluble tetrazolium salt-1 (WST-1) cytotoxicity assays were used to calculate cell survival curves and half maximal inhibitory concentrations (IC50). Combination experiments with thiopurines with a fixed dose of 200 muM 5-ASA or 100 muM allopurinol were conducted in HepaRG cells. Caspase-3/7 activation was evaluated, and single cell electrophoresis analysis was performed. RESULTS: A time- and dose-related cytotoxic effect was seen with azathioprine (AZA) in all hepatoma cells, whereas Huh7 and HepG2 cells did not show toxicity to 6-mercaptopurine (6-MP). HepaRG cells expressed the highest levels of drug metabolising enzymes, and therefore, combination experiments were conducted in HepaRG cells. Addition of a non-toxic dose of allopurinol resulted in a twofold to threefold increased cytotoxicity of all thiopurines, which seemed to be mediated by apoptosis/DNA damage. CONCLUSION: The addition of allopurinol to thiopurines leads to a two-threefold increased cytotoxicity in HepaRG cells.

Published
2015

36. Biomarkers in Barrett's esophagus (review)

Author

Lieshout, E.M.M. van, Bedaf, M.M.G., Ekkel, M.P.C., Nijhoff, W.A., and Peters, W.H.M.

Subjects
Voeding en premaligne aandoeningen, Nutrition and premalignant diseases
Abstract

Item does not contain fulltext

Published
1998

38. Glutathione S-transferases and cancer

Author

Schipper, D.L., Wagenmans, M.J.M., Wagener, D.J.T., and Peters, W.H.M.

Subjects
Experimental diagnostics and therapy of malignancies, Blood Cells, Leukemia, Lymphoma, Mycoses, Voeding en premaligne aandoeningen, Nutrition and premalignant diseases, Bacterial Infections, Infection, Combined Modality Therapy, Magnetic Resonance Imaging
Abstract

Item does not contain fulltext

Published
1997

39. Duodenal mucosal risk markers in patients with familial adenomatous polyposis: effects of celecoxib/ursodeoxycholic acid co-treatment and comparison with patient controls

Author

Heumen, B.W.H van, Roelofs, H.M.J., Morsche, R.H.M. te, Nagengast, F.M., and Peters, W.H.M.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Translational research [ONCOL 3], Molecular gastro-enterology and hepatology Translational research [IGMD 2], neoplasms, digestive system diseases
Abstract

Contains fulltext : 125358.pdf (Publisher’s version ) (Open Access) BACKGROUND: Familial adenomatous polyposis (FAP) is a disease characterized by the development of hundreds to thousands of adenomatous polyps in the colorectum early in life. Virtually all patients with FAP will develop colorectal cancer before the age of 40 to 50 years, unless prophylactic colectomy is performed, which significantly improves their prognosis. The mortality pattern has changed and duodenal cancer now is one of the main cancer-related causes of death in these patients. Practically all patients with FAP develop premalignant duodenal adenomas, which may develop to duodenal cancer in approximately 3-7% of patients. Duodenal cancer in patients with FAP has a poor prognosis. The clinical challenge is to identify patients at high-risk for duodenal carcinoma. Chemoprevention would be desirable to avoid duodenectomy. The main goal of this study is to identify risk markers in normal duodenal mucosa of patients with FAP, that could help identify patients at increased risk for malignant transformation. METHODS: Messenger RNA (mRNA) levels of glutathione S-transferase A1 (GSTA1), glutathione S-transferase P1 (GSTP1), KIAA1199, E-cadherin, peroxisome proliferative activated receptor delta (PPARdelta), caspase-3, cyclin D1, beta-catenin, and cyclooxygenase-2 (COX-2) were measured in duodenal mucosa, using the QuantiGene 2.0 Plex assay. Levels in normal appearing mucosa of patients with FAP (n = 37) were compared with levels in non-FAP patient controls (n = 16). In addition, levels before and after treatment with either celecoxib & ursodeoxycholic acid (UDCA, n = 14) or celecoxib & placebo (n = 13) were evaluated in patients with FAP. RESULTS: mRNA levels of glutathione S-transferase A1 (28.16% vs. 38.24%, p = 0.008) and caspase-3 (3.30% vs. 5.31%, p = 0.001) were significantly lower in patients with FAP vs. non-FAP patient controls, respectively. COX-2 mRNA levels in normal duodenal mucosa of patients with FAP were found to be unexpectedly low. None of the potential risk markers was influenced by celecoxib or celecoxib & UDCA. CONCLUSIONS: Protection against toxins and carcinogens (GSTA1) and apoptosis (caspase-3) is low in patients with FAP, which could contribute to increased susceptibility for malignant transformation of duodenal mucosa. TRIAL REGISTRATION: http://ClinicalTrials.gov number NCT00808743.

Published
2013

40. Barrett associated MHC and FOXF1 variants also increase esophageal carcinoma risk

Author

Dura, P., Veen, E.M. van, Salomon, J., Morsche, R.H.M. te, Roelofs, H.M.J., Kristinsson, J.O., Wobbes, T., Witteman, B.J., Tan, A.C., Drenth, J.P.H., and Peters, W.H.M.

Subjects
Molecular gastro-enterology and hepatology Membrane transport and intracellular motility [IGMD 2], Molecular gastro-enterology and hepatology [IGMD 2], Molecular gastro-enterology and hepatology Translational research [IGMD 2], digestive system diseases
Abstract

Contains fulltext : 118052.pdf (Publisher’s version ) (Closed access) Barrett's esophagus, with gastroesophageal reflux disease and obesity as risk factors, predisposes to esophageal adenocarcinoma (EAC). Recently a British genome wide association study identified two Barrett's esophagus susceptibility loci mapping within the major histocompatibility complex (MHC; rs9257809) and closely to the Forkhead-F1 (FOXF1; rs9936833) coding gene. An interesting issue is whether polymorphisms associated with Barrett's esophagus, are also implicated in esophageal carcinoma (EC), and more specifically EAC genesis. Assessing the individual genetic susceptibility can help identify high risk patients more prone to benefit from surveillance programs. Our hypothesis: Barrett associated MHC and FOXF1 variants modify EC risk in Caucasians. In a Dutch case-control study, 431 patients with EC and 605 healthy controls were included. Polymorphisms at chromosomes 6p21 (MHC) and 16q24 (FOXF1) were determined by means of real-time polymerase chain reaction (RT-PCR). Logistic regression analysis was used to calculate odds ratios with 95% confidence intervals. The FOXF1 rs9936833 variant C allele was associated with an increased EAC susceptibility; OR, [95% CI]; 1.21, [0.99-1.47]. A sex-stratified analysis revealed a similar association in males; 1.24 [1.00-1.55]. The variant MHC rs9257809 G allele as well as the MHC heterozygous AG genotype significantly increased ESCC risk; 1.76 [1.16-2.66] and 1.74 [1.08-2.80], respectively. Sex-stratification showed that the variant G allele was especially present in female patients; 2.32 [1.04-5.20]. In conclusion, this study provides evidence that MHC rs9257809 and FOXF1 rs9936833 variants, associated with Barrett's esophagus, also increase ESCC and EAC susceptibility in Caucasians. FOX proteins are transcription factors involved in organogenesis of the GI tract, while MHC haplotypes are strongly associated with smoking behavior, a crucial risk factor for ESCC. Assessing the individual genetic susceptibility can help identify high risk patients more prone to benefit from (Barrett) surveillance programs.

Published
2013

42. Immunohistochemical determination of glutathione S-transferase in gastric carcinomas and in adjacent normal gastric epithelium

Author

Schipper, D.L., Wagenmans, M.J.M., Haelst, U.J.G. van, Peters, W.H.M., Wobbes, T., Verhofstad, A.A.J., Lange, W., and Wagener, D.J.T.

Subjects
Free Radicals, Anastomosis, Multiple Organ Failure, mogelijke oorzaken en gevolgen (sepsis en ontsteking) [Sepsis en niet-bacteriële gegeneraliseerde ontsteking], Angiogenesis Factor, causes and effects (sepsis and inflammation) [Sepsis and non-bacterial generalized inflammation], Autonomic Nervous System, Laboratory, Foot Diseases, Surgical, Neoplasms, Sepsis, Diagnosis, Econometric and Statistical Methods: Special Topics, Preventive Health Services, Tumor pathology, Neoplasm Metastasis, The role of glutathione S-transferase P-170 glycoprotein and cell kinetics in drug resistance of gastric carcinoma, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Inflammation, Animal, Multiple Trauma, Anastomosis, Surgical, Voeding en premaligne aandoeningen, Special Topics [Econometric and Statistical Methods], Hand Injuries, Nutrition and premalignant diseases, Chirurgische Oncologie, Tumor pathologie, De rol van glutathion S-transferase, P-170 glycoproteine en celkinetische parameters voor cytostatica resistentie bij maagkanker, Diagnosis, Laboratory, Extracellular Matrix, Disease Models, Animal, Surgical Oncology, Disease Models, Wounds and Injuries, Inflammation Mediators
Abstract

Contains fulltext : 24078___.PDF (Publisher’s version ) (Open Access)

Published
1996

44. Glutathione S-transferase Pi in colorectal tumors is predictive for overall survival

Author

Mulder, T.P.J., Verspaget, H.W., Sier, C.F.M., Roelofs, H.M.J., Ganesh, S., Griffioen, G., and Peters, W.H.M.

Subjects
Voeding en premaligne aandoeningen, Nutrition and premalignant diseases, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Contains fulltext : 22116___.PDF (Publisher’s version ) (Open Access)

Published
1995

45. STAT1 gene mutation is not implicated in upper aerodigestive cancers

Author

Dura, P., Te Morsche, R., Lacko, M., Netea, M.G., Meer, J.W.M. van der, Drenth, J.P.H., and Peters, W.H.M.

Subjects
Pathogenesis and modulation of inflammation Infection and autoimmunity [N4i 1], Molecular gastro-enterology and hepatology Membrane transport and intracellular motility [IGMD 2], Molecular gastro-enterology and hepatology [IGMD 2], Molecular gastro-enterology and hepatology Translational research [IGMD 2], GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Contains fulltext : 109438.pdf (Publisher’s version ) (Open Access)

Published
2012

47. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

Author

Horwitz, M.S., McKay, J.D., Truong, T., Gaborieau, V., Chabrier, A., Chuang, S.-C., Byrnes, G., Zaridze, D., Shangina, O., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Bucur, A., Bencko, V., Holcatova, I., Janout, V., Foretova, L., Lagiou, P., Trichopoulos, D., Benhamou, S., Bouchardy, C., Ahrens, W., Merletti, F., Richiardi, L., Talamini, R., Barzan, L., Kjaerheim, K., Macfarlane, G.J., Macfarlane, T.V., Simonato, L., Canova, C., Agudo, A., Castellsagué, X., Lowry, R., Conway, D.I., McKinney, P.A., Healy, C.M., Toner, M.E., Znaor, A., Curado, M.P., Koifman, S., Menezes, A., Wünsch-Filho, V., Neto, J.E., Garrote, L.F., Boccia, S., Cadoni, G., Arzani, D., Olshan, A.F., Weissler, M.C., Funkhouser, W.K., Luo, J., Lubiński, J., Trubicka, J., Lener, M., Oszutowska, D., Schwartz, S.M., Chen, C., Fish, S., Doody, D.R., Muscat, J.E., Lazarus, P., Gallagher, C.J., Chang, S.C., Zhang, Z.F., Wei, Q., Sturgis, E.M., Wang, L.E., Franceschi, S., Herrero, R., Kelsey, K.T., McClean, M.D., Marsit, C.J., Nelson, H.H., Romkes, M., Buch, S., Nukui, T., Zhong, S., Lacko, M., Manni, J.J., Peters, W.H.M., Hung, R.J., McLaughlin, J., Vatten, L., Njølstad, I., Goodman, G.E., Field, J.K., Liloglou, T., Vineis, P., Clavel-Chapelon, F., Palli, D., Tumino, R., Krogh, V., Panico, S., González, C.A., Quirós, J.R., Martínez, C., Navarro, C., Ardanaz, E., Larrañaga, N., Khaw, K.T., Key, T., Bueno-de-Mesquita, H. B., Peeters, P.H.M., Trichopoulou, A., Linseisen, J., Boeing, H., Hallmans, G., Overvad, K., Tjønneland, A., Kumle, M., Riboli, E., Välk, K., Vooder, T., Metspalu, A., Zelenika, D., Boland, A., Delepine, M., Foglio, M., Lechner, D., Blanché, H., Gut, I.G., Galan, P., Heath, S., Hashibe, M., Hayes, R.B., Boffetta, P., Lathrop, M., and Brennan, P.

Abstract

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Published
2011

48. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

Author

McKay, J.D., Truong, T., Gaborieau, V., Chabrier, A., Chuang, S.C., Byrnes, G., Zaridze, D., Shangina, O., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Bucur, A., Bencko, V., Holcatova, I., Janout, V., Foretova, L., Lagiou, P., Trichopoulos, D., Benhamou, S., Bouchardy, C., Ahrens, W., Merletti, F., Richiardi, L., Talamini, R., Barzan, L., Kjaerheim, K., Macfarlane, G.J., Macfarlane, T.V., Simonato, L., Canova, C., Agudo, A., Castellsague, X., Lowry, R., Conway, D.I., McKinney, P.A., Healy, C.M., Toner, M.E., Znaor, A., Curado, M.P., Koifman, S., Menezes, A., Wunsch-Filho, V., Neto, J.E., Garrote, L.F., Boccia, S., Cadoni, G., Arzani, D., Olshan, A.F., Weissler, M.C., Funkhouser, W.K., Luo, J., Lubinski, J., Trubicka, J., Lener, M., Oszutowska, D., Schwartz, S.M., Chen, C., Fish, S., Doody, D.R., Muscat, J.E., Lazarus, P., Gallagher, C.J., Chang, S.C., Zhang, Z.F., Wei, Q., Sturgis, E.M., Wang, L.E., Franceschi, S., Herrero, R., Kelsey, K.T., McClean, M.D., Marsit, C.J., Nelson, H.H., Romkes, M., Buch, S., Nukui, T., Zhong, S., Lacko, M., Manni, J.J., Peters, W.H.M., Hung, R.J., McLaughlin, J., Vatten, L., Njolstad, I., Goodman, G.E., Field, J.K., Liloglou, T., Vineis, P., Clavel-Chapelon, F., Palli, D., Tumino, R., Krogh, V., Panico, S., Gonzalez, C.A., Quiros, J.R., Martinez, C., Navarro, C, Ardanaz, E., and Larrañaga, N.

Abstract

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p

Published
2011

49. A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers

Author

Chen, D. Truong, T. Gaborieau, V. Byrnes, G. Chabrier, A. Chuang, S.-C. Olshan, A.F. Weissler, M.C. Luo, J. Romkes, M. Buch, S. Nukui, T. Franceschi, S. Herrero, R. Talamini, R. Kelsey, K.T. Christensen, B. McClean, M.D. Lacko, M. Manni, J.J. Peters, W.H.M. Lubiński, J. Trubicka, J. Lener, M. Muscat, J.E. Lazarus, P. Wei, Q. Sturgis, E.M. Zhang, Z.-F. Chang, S.-C. Wang, R. Schwartz, S.M. Chen, C. Benhamou, S. Lagiou, P. Holcátová, I. Richiardi, L. Kjaerheim, K. Agudo, A. Castellsagué, X. Macfarlane, T.V. Barzan, L. Canova, C. Thakker, N.S. Conway, D.I. Znaor, A. Healy, C.M. Ahrens, W. Zaridze, D. Szeszenia-Dabrowska, N. Lissowska, J. Fabianova, E. Bucur, A. Bencko, V. Foretova, L. Janout, V. Curado, M.P. Koifman, S. Menezes, A. Wünsch-Filho, V. Eluf-Neto, J. Fernandez, L. Boccia, S. Hashibe, M. Hayes, R.B. Boffetta, P. Brennan, P. McKay, J.D.

Abstract

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case - control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P het) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 × 10 -6) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P het = 6 × 10-4). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations.©2011 AACR.

Published
2011

50. Polymorphisms in the insulin-like growth factor axis are associated with gastrointestinal cancer

Author

Ong, J., Salomon, J., Morsche, R.H.M. te, Roelofs, H.M.J., Witteman, B.J., Dura, P., Lacko, M., Peters, W.H.M., Ong, J., Salomon, J., Morsche, R.H.M. te, Roelofs, H.M.J., Witteman, B.J., Dura, P., Lacko, M., and Peters, W.H.M.

Abstract

Contains fulltext : 136543.pdf (publisher's version ) (Open Access), INTRODUCTION: Numerous factors influence the development of gastrointestinal (GI) cancer. The insulin-like growth factor (IGF) axis plays a role in embryonic and postnatal growth and tissue repair. Elevated levels of IGFs, low levels of IGF binding proteins (IGFBPs) and over-expression of IGF receptor (IGFR-I) were associated with several stages of cancer. Here, the prevalence of the single nucleotide polymorphisms (SNPs) rs6214 in the IGF type I (IGF-I) gene and rs6898743 in the growth hormone receptor (GHR) gene in patients with GI cancer and controls was studied. MATERIALS & METHODS: In this Dutch case-control study, DNA isolated from blood of 1,457 GI cancer patients; 438 patients with head and neck cancer (HNC), 475 with esophageal cancer (EC) and 544 with colorectal cancer (CRC) and 1,457 matched controls, was used to determine the rs6214 and rs6898743 genotypes by polymerase chain reaction. The association between these SNPs and GI cancer, HNC, esophageal adenocarcinoma (EAC), esophageal squamous-cell carcinoma (ESCC) and proximal or distal CRC was studied. Odds ratios (ORs) with 95% confidence interval (95% CI) were calculated via unconditional logistic regression. RESULTS: Overall for GI cancer, the ORs for SNPs rs6214 and rs6898743 were approximately 1.0 (p-value>0.05), using the most common genotypes GG as reference. An OR of 1.54 (95% CI, 1.05-2.27) was found for EC for genotype AA of rs6214. The ORs for EAC were 1.45 (95% CI, 1.04-2.01) and 1.71 (95% CI, 1.10-2.68), for genotypes GA and AA, respectively. Genotype GC of rs6898743 showed an OR of 0.47 (95% CI, 0.26-0.86) for ESCC. CONCLUSION: The A allele of SNP rs6214 in the IGF-I gene was associated with EAC, and with HNC in women. The GC genotype of rs6898743 in the GHR gene was negatively associated with ESCC.

Published
2014

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