Article: Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer

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TitleRefinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer
AuthorsPittman, AM4
Webb, E4
CarvajalCarmona, L14
Howarth, K14
Di Bernardo, MC4
Broderick, P4
Spain, S14
Walther, A14
Price, A4
Sullivan, K4
Twiss, P4
Fielding, S4
Rowan, A14
Jaeger, E14
Vijayakrishnan, J4
Chandler, I4
Penegar, S4
Qureshi, M4
Lubbe, S4
Domingo, E14
Kemp, Z14
Barclay, E14
Wood, W4
Martin, L1 3 12 14 23
Gorman, M4
Thomas, H22
Peto, J4 9
Bishop, T15
Gray, R12
Maher, ER1 12
Lucassen, A3
Kerr, D16
Evans, GR23
van Wezel, T20
Morreau, H20
Wijnen, JT20
Hopper, JL19
Southey, MC13
Giles, GG2 19
Severi, G2
CastellvíBel, S18
RuizPonte, C5
Carracedo, A5
Castells, A18
Försti, A11 24
Hemminki, K11 24
Vodicka, P21
Naccarati, A21
Lipton, L17
Ho, JWC6
Cheng, KK6
Sham, PC6
Luk, J6
Agúndez, JAG7
Ladero, JM8
de la Hoya, M8
Caldés, T8
Niittymäki, I10
Tuupanen, S10
Karhu, A10
Aaltonen, LA10
Cazier, JB14
Tomlinson, IPM14
Houlston, RS4
Issue Date2008
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
CitationHuman Molecular Genetics, 2008, v. 17 n. 23, p. 3720-3727 [How to Cite?]
DOI: http://dx.doi.org/10.1093/hmg/ddn267
AbstractThe common single-nucleotide polymorphism (SNP) rs3802842 at 11q23.1 has recently been reported to be associated with risk of colorectal cancer (CRC). To examine this association in detail we genotyped rs3802842 in eight independent case-control series comprising a total of 10 638 cases and 10 457 healthy individuals. A significant association between the C allele of rs3802842 and CRC risk was found (per allele OR = 1.17; 95% confidence interval [CI]: 1.12-1.22; P = 1.08 × 10 -12) with the risk allele more frequent in rectal than colonic disease (P = 0.02). In combination with 8q21, 8q24, 10p14, 11q, 15q13.3 and 18q21 variants, the risk of CRC increases with an increasing numbers of variant alleles for the six loci (OR per allele = 1.19; 95% CI: 1.15-1.23; P trend = 7.4 × 10 -24). Using the data from our genome-wide association study of CRC, LD mapping and imputation, we were able to refine the location of the causal locus to a 60 kb region and screened for coding changes. The absence of exonic mutations in any of the transcripts (FLJ45803, LOC120376, C11orf53 and POU2AF1) mapping to this region makes the association likely to be a consequence of non-coding effects on gene expression. © The Author 2008. Published by Oxford University Press. All rights reserved.
ISSN0964-6906
2011 Impact Factor: 7.636
2011 SCImago Journal Rankings: 1.308
DOIhttp://dx.doi.org/10.1093/hmg/ddn267
ISI Accession Number IDWOS:000260980800010
Funding AgencyGrant Number
Cancer Research UK
Institute of Cancer Research
European UnionLSHC-CT-2004-503465
Bobby Moore Fund
CORE
Thomas Falknor Fund
St. George's Hospital Medical School
Fondo de Investigacion Sanitaria03/0070
05/0071
05/2031
Ministerio de Educacion y CienciaSAF 04-07190
07-64873
Asociacion Espanola contra el Cancer
Merck, Co
Xunta de GaliciaPGI-DIT07PXIB9101209PR
Fundacion Olga Torres
Fundacion de Investigacion Medica Mutua Madrilena
Instituto de Salud Carlos III
Ministerio de Sanidad
FIS051056
RD07/0064/0016
Instituto de Salud Carlos III, Madrid, Spain
Academy of Finland
Finnish Cancer Society
Sigrid Juselius Foundation
European Commission9LSHG-CT2004-512142
Deutsche Krebshilfe
German Ministry of Education and Research01GS0426
01GR0468
Medical Faculty, Kiel
Federal Ministry of Education and ResearchZZ9603
Ministry of Cultural Affairs
Social Ministry of the Federal State of Mecklenburg-West Pomerania. Leiden
Dutch Cancer SocietyUL2005-3247
Medical Ethical CommitteeP01.019
Dutch Federation of Medical Sciences, Madrid
Fondo Investigacion SanitariaPI070316
RD06/0020/0021
National Health and Medical Research Council (NHMRC)209057
251533
396414
Cancer Council Victoria
NHMRC Australia
GACR310/07/1430
Funding Information:

Cancer Research UK provided principal funding for this study. Institute of Cancer Research: Additional funding was provided by the European Union (CPRB LSHC-CT-2004-503465), the Bobby Moore Fund, CORE and the Thomas Falknor Fund. I. C. was in receipt of a clinical training fellowship from St. George's Hospital Medical School. London Institute: Additional funding was provided by CORE and the Bobby Moore Fund. Barcelona: We are sincerely grateful to all patients participating in this study that were recruited in 25 Spanish hospitals as part of the EPI-COLON project. This work was supported by grants from the Fondo de Investigacion Sanitaria (03/0070, 05/0071 and 05/2031), from the Ministerio de Educacion y Ciencia (SAF 04-07190 and 07-64873), the Asociacion Espanola contra el Cancer, from Merck, Co, from the Xunta de Galicia (PGI-DIT07PXIB9101209PR), from Fundacion Olga Torres (S. C.- B.), and from Fundacion de Investigacion Medica Mutua Madrilena (C. R.- P.). CIBEREHD and CIBERER are funded by the Instituto de Salud Carlos III. S. C.- B. is supported by a contract from the Fondo de Investigacion Sanitaria ( CP 03-0070, Ministerio de Sanidad). Extremadura: Work was supported by grants FIS 051056 and RD07/0064/0016 from Instituto de Salud Carlos III, Madrid, Spain. Finland: This work was supported by grants from Academy of Finland ( Finnish Centre of Excellence Program 2006 - 2011), the Finnish Cancer Society, the Sigrid Juselius Foundation and the European Commission 9LSHG-CT2004-512142). Heidelberg: Supported by Deutsche Krebshilfe and the Swedish Cancer Society. Kiel: This study was supported by the German Ministry of Education and Research through the National Genome Research Network through the POPGEN biobank project ( 01GS0426, 01GR0468) and the Medical Faculty, Kiel. The SHIP recuitment project is funded by the Federal Ministry of Education and Research ( ZZ9603), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Leiden: DFCCS was supported by Dutch Cancer Society grant UL2005-3247 and approved by the local Medical Ethical Committee ( protocol P01.019); samples were handled according to Code Proper Secondary Use of Human Tissue by the Dutch Federation of Medical Sciences (www.federa.org). Madrid: Work was supported by the Fondo Investigacion Sanitaria (PI070316 and RD06/0020/0021). Melbourne: The Melbourne Collaborative Cohort Study is supported by National Health and Medical Research Council (NHMRC) grants 209057, 251533 and 396414 and receives core funding and infrastructure support from the The Cancer Council Victoria. J. L. H. is a NHMRC Australia Fellow and M. C. S. is a NHMRC Senior Research Fellow. We would like to acknowledge Mr Fabrice Odefrey for performing the genotyping. Prague: Supported by the grant GACR310/07/1430.

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorPittman, AM
dc.contributor.authorWebb, E
dc.contributor.authorCarvajalCarmona, L
dc.contributor.authorHowarth, K
dc.contributor.authorDi Bernardo, MC
dc.contributor.authorBroderick, P
dc.contributor.authorSpain, S
dc.contributor.authorWalther, A
dc.contributor.authorPrice, A
dc.contributor.authorSullivan, K
dc.contributor.authorTwiss, P
dc.contributor.authorFielding, S
dc.contributor.authorRowan, A
dc.contributor.authorJaeger, E
dc.contributor.authorVijayakrishnan, J
dc.contributor.authorChandler, I
dc.contributor.authorPenegar, S
dc.contributor.authorQureshi, M
dc.contributor.authorLubbe, S
dc.contributor.authorDomingo, E
dc.contributor.authorKemp, Z
dc.contributor.authorBarclay, E
dc.contributor.authorWood, W
dc.contributor.authorMartin, L
dc.contributor.authorGorman, M
dc.contributor.authorThomas, H
dc.contributor.authorPeto, J
dc.contributor.authorBishop, T
dc.contributor.authorGray, R
dc.contributor.authorMaher, ER
dc.contributor.authorLucassen, A
dc.contributor.authorKerr, D
dc.contributor.authorEvans, GR
dc.contributor.authorvan Wezel, T
dc.contributor.authorMorreau, H
dc.contributor.authorWijnen, JT
dc.contributor.authorHopper, JL
dc.contributor.authorSouthey, MC
dc.contributor.authorGiles, GG
dc.contributor.authorSeveri, G
dc.contributor.authorCastellvíBel, S
dc.contributor.authorRuizPonte, C
dc.contributor.authorCarracedo, A
dc.contributor.authorCastells, A
dc.contributor.authorFörsti, A
dc.contributor.authorHemminki, K
dc.contributor.authorVodicka, P
dc.contributor.authorNaccarati, A
dc.contributor.authorLipton, L
dc.contributor.authorHo, JWC
dc.contributor.authorCheng, KK
dc.contributor.authorSham, PC
dc.contributor.authorLuk, J
dc.contributor.authorAgúndez, JAG
dc.contributor.authorLadero, JM
dc.contributor.authorde la Hoya, M
dc.contributor.authorCaldés, T
dc.contributor.authorNiittymäki, I
dc.contributor.authorTuupanen, S
dc.contributor.authorKarhu, A
dc.contributor.authorAaltonen, LA
dc.contributor.authorCazier, JB
dc.contributor.authorTomlinson, IPM
dc.contributor.authorHoulston, RS
dc.date.accessioned2010-05-31T03:55:36Z
dc.date.available2010-05-31T03:55:36Z
dc.date.issued2008
dc.description.abstractThe common single-nucleotide polymorphism (SNP) rs3802842 at 11q23.1 has recently been reported to be associated with risk of colorectal cancer (CRC). To examine this association in detail we genotyped rs3802842 in eight independent case-control series comprising a total of 10 638 cases and 10 457 healthy individuals. A significant association between the C allele of rs3802842 and CRC risk was found (per allele OR = 1.17; 95% confidence interval [CI]: 1.12-1.22; P = 1.08 × 10 -12) with the risk allele more frequent in rectal than colonic disease (P = 0.02). In combination with 8q21, 8q24, 10p14, 11q, 15q13.3 and 18q21 variants, the risk of CRC increases with an increasing numbers of variant alleles for the six loci (OR per allele = 1.19; 95% CI: 1.15-1.23; P trend = 7.4 × 10 -24). Using the data from our genome-wide association study of CRC, LD mapping and imputation, we were able to refine the location of the causal locus to a 60 kb region and screened for coding changes. The absence of exonic mutations in any of the transcripts (FLJ45803, LOC120376, C11orf53 and POU2AF1) mapping to this region makes the association likely to be a consequence of non-coding effects on gene expression. © The Author 2008. Published by Oxford University Press. All rights reserved.
dc.description.naturelink_to_subscribed_fulltext
dc.identifier.citationHuman Molecular Genetics, 2008, v. 17 n. 23, p. 3720-3727 [How to Cite?]
DOI: http://dx.doi.org/10.1093/hmg/ddn267
dc.identifier.doihttp://dx.doi.org/10.1093/hmg/ddn267
dc.identifier.epage3727
dc.identifier.hkuros157998
dc.identifier.isiWOS:000260980800010
Funding AgencyGrant Number
Cancer Research UK
Institute of Cancer Research
European UnionLSHC-CT-2004-503465
Bobby Moore Fund
CORE
Thomas Falknor Fund
St. George's Hospital Medical School
Fondo de Investigacion Sanitaria03/0070
05/0071
05/2031
Ministerio de Educacion y CienciaSAF 04-07190
07-64873
Asociacion Espanola contra el Cancer
Merck, Co
Xunta de GaliciaPGI-DIT07PXIB9101209PR
Fundacion Olga Torres
Fundacion de Investigacion Medica Mutua Madrilena
Instituto de Salud Carlos III
Ministerio de Sanidad
FIS051056
RD07/0064/0016
Instituto de Salud Carlos III, Madrid, Spain
Academy of Finland
Finnish Cancer Society
Sigrid Juselius Foundation
European Commission9LSHG-CT2004-512142
Deutsche Krebshilfe
German Ministry of Education and Research01GS0426
01GR0468
Medical Faculty, Kiel
Federal Ministry of Education and ResearchZZ9603
Ministry of Cultural Affairs
Social Ministry of the Federal State of Mecklenburg-West Pomerania. Leiden
Dutch Cancer SocietyUL2005-3247
Medical Ethical CommitteeP01.019
Dutch Federation of Medical Sciences, Madrid
Fondo Investigacion SanitariaPI070316
RD06/0020/0021
National Health and Medical Research Council (NHMRC)209057
251533
396414
Cancer Council Victoria
NHMRC Australia
GACR310/07/1430
Funding Information:

Cancer Research UK provided principal funding for this study. Institute of Cancer Research: Additional funding was provided by the European Union (CPRB LSHC-CT-2004-503465), the Bobby Moore Fund, CORE and the Thomas Falknor Fund. I. C. was in receipt of a clinical training fellowship from St. George's Hospital Medical School. London Institute: Additional funding was provided by CORE and the Bobby Moore Fund. Barcelona: We are sincerely grateful to all patients participating in this study that were recruited in 25 Spanish hospitals as part of the EPI-COLON project. This work was supported by grants from the Fondo de Investigacion Sanitaria (03/0070, 05/0071 and 05/2031), from the Ministerio de Educacion y Ciencia (SAF 04-07190 and 07-64873), the Asociacion Espanola contra el Cancer, from Merck, Co, from the Xunta de Galicia (PGI-DIT07PXIB9101209PR), from Fundacion Olga Torres (S. C.- B.), and from Fundacion de Investigacion Medica Mutua Madrilena (C. R.- P.). CIBEREHD and CIBERER are funded by the Instituto de Salud Carlos III. S. C.- B. is supported by a contract from the Fondo de Investigacion Sanitaria ( CP 03-0070, Ministerio de Sanidad). Extremadura: Work was supported by grants FIS 051056 and RD07/0064/0016 from Instituto de Salud Carlos III, Madrid, Spain. Finland: This work was supported by grants from Academy of Finland ( Finnish Centre of Excellence Program 2006 - 2011), the Finnish Cancer Society, the Sigrid Juselius Foundation and the European Commission 9LSHG-CT2004-512142). Heidelberg: Supported by Deutsche Krebshilfe and the Swedish Cancer Society. Kiel: This study was supported by the German Ministry of Education and Research through the National Genome Research Network through the POPGEN biobank project ( 01GS0426, 01GR0468) and the Medical Faculty, Kiel. The SHIP recuitment project is funded by the Federal Ministry of Education and Research ( ZZ9603), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Leiden: DFCCS was supported by Dutch Cancer Society grant UL2005-3247 and approved by the local Medical Ethical Committee ( protocol P01.019); samples were handled according to Code Proper Secondary Use of Human Tissue by the Dutch Federation of Medical Sciences (www.federa.org). Madrid: Work was supported by the Fondo Investigacion Sanitaria (PI070316 and RD06/0020/0021). Melbourne: The Melbourne Collaborative Cohort Study is supported by National Health and Medical Research Council (NHMRC) grants 209057, 251533 and 396414 and receives core funding and infrastructure support from the The Cancer Council Victoria. J. L. H. is a NHMRC Australia Fellow and M. C. S. is a NHMRC Senior Research Fellow. We would like to acknowledge Mr Fabrice Odefrey for performing the genotyping. Prague: Supported by the grant GACR310/07/1430.

dc.identifier.issn0964-6906
2011 Impact Factor: 7.636
2011 SCImago Journal Rankings: 1.308
dc.identifier.issue23
dc.identifier.openurl
dc.identifier.pmid18753146
dc.identifier.scopuseid_2-s2.0-56049119387
dc.identifier.spage3720
dc.identifier.urihttp://hdl.handle.net/10722/59697
dc.identifier.volume17
dc.languageeng
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
dc.publisher.placeUnited Kingdom
dc.relation.ispartofHuman Molecular Genetics
dc.relation.referencesReferences in Scopus
dc.rightsHuman Molecular Genetics. Copyright © Oxford University Press.
dc.titleRefinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer
dc.typeArticle
Author Affiliations
  1. Birmingham Women's Hospital
  2. Cancer Council Victoria
  3. University of Southampton
  4. Institute of Cancer Research London
  5. Complejo Hospitalario Universitario de Santiago
  6. The University of Hong Kong
  7. Universidad de Extremadura
  8. Hospital Clinico San Carlos de Madrid
  9. London School of Hygiene & Tropical Medicine
  10. University of Helsinki Faculty of Medicine
  11. Karolinska Institutet
  12. University of Birmingham
  13. University of Melbourne School of Medicine Dentistry and Health Sciences
  14. Cancer Research UK
  15. University of Leeds
  16. University of Oxford
  17. Western Hospital, Footscray
  18. CIBER Enfermedades Hepaticas y Digestivas
  19. University of Melbourne
  20. Leiden University Medical Center - LUMC
  21. Institute of Experimental Medicine of the Academy of Sciences of the Czech Republic
  22. St. Mark's Hospital and Academic Institute
  23. St Mary's Hospital London
  24. German Cancer Research Center