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

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

The 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 (ORper allele = 1.19; 95% CI: 1.15-1.23; Ptrend = 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.

0964-6906
3720-3727
Pittman, Alan M.
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Castells, Antoni
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Ho, Judy W.C.
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Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer
Pittman, Alan M.
d21a7fc2-97fe-43bb-836f-3037d9c6cb89
Webb, Emily
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Carvajal-Carmona, Luis
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Howarth, Kimberley
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Di Bernardo, Maria Chiara
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Broderick, Peter
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Spain, Sarah
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Walther, Axel
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Price, Amy
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Sullivan, Kate
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Twiss, Philip
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Fielding, Sarah
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Rowan, Andrew
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Jaeger, Emma
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Vijayakrishnan, Jayaram
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Chandler, Ian
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Penegar, Steven
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Qureshi, Mobshra
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Lubbe, Steven
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Domingo, Enric
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Kemp, Zoe
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Barclay, Ella
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Wood, Wendy
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Martin, Lynn
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Gorman, Maggie
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Thomas, Huw
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Peto, Julian
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Bishop, Timothy
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Gray, Richard
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Maher, Eamonn R.
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Lucassen, Anneke
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van Wezel, Tom
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Morreau, Hans
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Hopper, John L.
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Southey, Melissa C.
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Severi, Gianluca
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Castellví-Bel, Sergi
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Ruiz-Ponte, Clara
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Carracedo, Angel
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Castells, Antoni
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Försti, Asta
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Hemminki, Kari
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Vodicka, Pavel
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Naccarati, Alessio
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Ho, Judy W.C.
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Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer (2008) Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer. Human Molecular Genetics, 17 (23), 3720-3727. (doi:10.1093/hmg/ddn267).

Record type: Article

Abstract

The 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 (ORper allele = 1.19; 95% CI: 1.15-1.23; Ptrend = 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.

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More information

Published date: 27 August 2008
Additional Information: 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 Investigación Sanitaria (03/0070, 05/0071 and 05/ 2031), from the Ministerio de Educación y Ciencia (SAF 04-07190 and 07-64873), the Asociación Española contra el Cáncer, from Merck, Co, from the Xunta de Galicia (PGI-DIT07PXIB9101209PR), from Fundacion Olga Torres (S.C.-B.), and from Fundación de Investigación Médica Mútua Madrileña (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 Investigación 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-CT-2004-512142). 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 recuit-ment 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 GACR 310/07/1430.

Identifiers

Local EPrints ID: 469600
URI: http://eprints.soton.ac.uk/id/eprint/469600
ISSN: 0964-6906
PURE UUID: 8017d9ca-e033-4493-8aba-583496898388
ORCID for Anneke Lucassen: ORCID iD orcid.org/0000-0003-3324-4338

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Date deposited: 21 Sep 2022 16:33
Last modified: 18 Mar 2024 02:54

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Contributors

Author: Alan M. Pittman
Author: Emily Webb
Author: Luis Carvajal-Carmona
Author: Kimberley Howarth
Author: Maria Chiara Di Bernardo
Author: Peter Broderick
Author: Sarah Spain
Author: Axel Walther
Author: Amy Price
Author: Kate Sullivan
Author: Philip Twiss
Author: Sarah Fielding
Author: Andrew Rowan
Author: Emma Jaeger
Author: Jayaram Vijayakrishnan
Author: Ian Chandler
Author: Steven Penegar
Author: Mobshra Qureshi
Author: Steven Lubbe
Author: Enric Domingo
Author: Zoe Kemp
Author: Ella Barclay
Author: Wendy Wood
Author: Lynn Martin
Author: Maggie Gorman
Author: Huw Thomas
Author: Julian Peto
Author: Timothy Bishop
Author: Richard Gray
Author: Eamonn R. Maher
Author: Anneke Lucassen ORCID iD
Author: David Kerr
Author: Gareth R. Evans
Author: Tom van Wezel
Author: Hans Morreau
Author: Juul T. Wijnen
Author: John L. Hopper
Author: Melissa C. Southey
Author: Graham G. Giles
Author: Gianluca Severi
Author: Sergi Castellví-Bel
Author: Clara Ruiz-Ponte
Author: Angel Carracedo
Author: Antoni Castells
Author: Asta Försti
Author: Kari Hemminki
Author: Pavel Vodicka
Author: Alessio Naccarati
Author: Lara Lipton
Author: Judy W.C. Ho
Corporate Author: Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer

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