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

Alan M. Pittman; Emily Webb; Luis Carvajal-Carmona; Kimberley Howarth; Maria Chiara Di Bernardo; Peter Broderick; Sarah Spain; Axel Walther; Amy Price; Kate Sullivan; Philip Twiss; Sarah Fielding; Andrew Rowan; Emma Jaeger; Jayaram Vijayakrishnan; Ian Chandler; Steven Penegar; Mobshra Qureshi; Steven Lubbe; Enric Domingo; Zoe Kemp; Ella Barclay; Wendy Wood; Lynn Martin; Maggie Gorman; Huw Thomas; Julian Peto; Timothy Bishop; Richard Gray; Eamonn R. Maher; Anneke Lucassen; David Kerr; Gareth R. Evans; Tom van Wezel; Hans Morreau; Juul T. Wijnen; John L. Hopper; Melissa C. Southey; Graham G. Giles; Gianluca Severi; Sergi Castellví-Bel; Clara Ruiz-Ponte; Angel Carracedo; Antoni Castells; Asta Försti; Kari Hemminki; Pavel Vodicka; Alessio Naccarati; Lara Lipton; Judy W.C. Ho; King Yip Cheng; Pak C. Sham; J. Luk; Jose A.G. Agúndez; Jose M. Ladero; Miguel de la Hoya; Trinidad Caldés; Iina Niittymäki; Sari Tuupanen; Auli Karhu; Lauri A. Aaltonen; Jean Baptiste Cazier; Ian P.M. Tomlinson; Richard S. Houlston

doi:10.1093/hmg/ddn267

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

Alan M. Pittman, Emily Webb, Luis Carvajal-Carmona, Kimberley Howarth, Maria Chiara Di Bernardo, Peter Broderick, Sarah Spain, Axel Walther, Amy Price, Kate Sullivan, Philip Twiss, Sarah Fielding, Andrew Rowan, Emma Jaeger, Jayaram Vijayakrishnan, Ian Chandler, Steven Penegar, Mobshra Qureshi, Steven Lubbe, Enric DomingoZoe Kemp, Ella Barclay, Wendy Wood, Lynn Martin, Maggie Gorman, Huw Thomas, Julian Peto, Timothy Bishop, Richard Gray, Eamonn R. Maher, Anneke Lucassen, David Kerr, Gareth R. Evans, Tom van Wezel, Hans Morreau, Juul T. Wijnen, John L. Hopper, Melissa C. Southey, Graham G. Giles, Gianluca Severi, Sergi Castellví-Bel, Clara Ruiz-Ponte, Angel Carracedo, Antoni Castells, Asta Försti, Kari Hemminki, Pavel Vodicka, Alessio Naccarati, Lara Lipton, Judy W.C. Ho, King Yip Cheng, Pak C. Sham, J. Luk, Jose A.G. Agúndez, Jose M. Ladero, Miguel de la Hoya, Trinidad Caldés, Iina Niittymäki, Sari Tuupanen, Auli Karhu, Lauri A. Aaltonen, Jean Baptiste Cazier, Ian P.M. Tomlinson, Richard S. Houlston

Research output: Journal article publication › Journal article › Academic research › peer-review

63 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3720-3727
Number of pages	8
Journal	Human Molecular Genetics
Volume	17
Issue number	23
DOIs	https://doi.org/10.1093/hmg/ddn267
Publication status	Published - 19 Nov 2008
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/hmg/ddn267

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Pittman, A. M., Webb, E., Carvajal-Carmona, L., Howarth, K., Di Bernardo, M. C., Broderick, P., Spain, S., Walther, A., Price, A., Sullivan, K., Twiss, P., Fielding, S., Rowan, A., Jaeger, E., Vijayakrishnan, J., Chandler, I., Penegar, S., Qureshi, M., Lubbe, S., ... Houlston, R. S. (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. https://doi.org/10.1093/hmg/ddn267

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

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.",

author = "Pittman, {Alan M.} and Emily Webb and Luis Carvajal-Carmona and Kimberley Howarth and {Di Bernardo}, {Maria Chiara} and Peter Broderick and Sarah Spain and Axel Walther and Amy Price and Kate Sullivan and Philip Twiss and Sarah Fielding and Andrew Rowan and Emma Jaeger and Jayaram Vijayakrishnan and Ian Chandler and Steven Penegar and Mobshra Qureshi and Steven Lubbe and Enric Domingo and Zoe Kemp and Ella Barclay and Wendy Wood and Lynn Martin and Maggie Gorman and Huw Thomas and Julian Peto and Timothy Bishop and Richard Gray and Maher, {Eamonn R.} and Anneke Lucassen and David Kerr and Evans, {Gareth R.} and {van Wezel}, Tom and Hans Morreau and Wijnen, {Juul T.} and Hopper, {John L.} and Southey, {Melissa C.} and Giles, {Graham G.} and Gianluca Severi and Sergi Castellv{\'i}-Bel and Clara Ruiz-Ponte and Angel Carracedo and Antoni Castells and Asta F{\"o}rsti and Kari Hemminki and Pavel Vodicka and Alessio Naccarati and Lara Lipton and Ho, {Judy W.C.} and Cheng, {King Yip} and Sham, {Pak C.} and J. Luk and Ag{\'u}ndez, {Jose A.G.} and Ladero, {Jose M.} and {de la Hoya}, Miguel and Trinidad Cald{\'e}s and Iina Niittym{\"a}ki and Sari Tuupanen and Auli Karhu and Aaltonen, {Lauri A.} and Cazier, {Jean Baptiste} and Tomlinson, {Ian P.M.} and Houlston, {Richard S.}",

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Pittman, AM, Webb, E, Carvajal-Carmona, L, Howarth, K, Di Bernardo, MC, Broderick, P, Spain, S, Walther, A, Price, A, Sullivan, K, Twiss, P, Fielding, S, Rowan, A, Jaeger, E, Vijayakrishnan, J, Chandler, I, Penegar, S, Qureshi, M, Lubbe, S, Domingo, E, Kemp, Z, Barclay, E, Wood, W, Martin, L, Gorman, M, Thomas, H, Peto, J, Bishop, T, Gray, R, Maher, ER, Lucassen, A, Kerr, D, Evans, GR, van Wezel, T, Morreau, H, Wijnen, JT, Hopper, JL, Southey, MC, Giles, GG, Severi, G, Castellví-Bel, S, Ruiz-Ponte, C, Carracedo, A, Castells, A, Försti, A, Hemminki, K, Vodicka, P, Naccarati, A, Lipton, L, Ho, JWC, Cheng, KY, Sham, PC, Luk, J, Agúndez, JAG, Ladero, JM, de la Hoya, M, Caldés, T, Niittymäki, I, Tuupanen, S, Karhu, A, Aaltonen, LA, Cazier, JB, Tomlinson, IPM & Houlston, RS 2008, 'Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer', Human Molecular Genetics, vol. 17, no. 23, pp. 3720-3727. https://doi.org/10.1093/hmg/ddn267

TY - JOUR

T1 - Refinement of the basis and impact of common 11q23.1 variation to the risk of developing colorectal cancer

AU - Pittman, Alan M.

AU - Webb, Emily

AU - Carvajal-Carmona, Luis

AU - Howarth, Kimberley

AU - Di Bernardo, Maria Chiara

AU - Broderick, Peter

AU - Spain, Sarah

AU - Walther, Axel

AU - Price, Amy

AU - Sullivan, Kate

AU - Twiss, Philip

AU - Fielding, Sarah

AU - Rowan, Andrew

AU - Jaeger, Emma

AU - Vijayakrishnan, Jayaram

AU - Chandler, Ian

AU - Penegar, Steven

AU - Qureshi, Mobshra

AU - Lubbe, Steven

AU - Domingo, Enric

AU - Kemp, Zoe

AU - Barclay, Ella

AU - Wood, Wendy

AU - Martin, Lynn

AU - Gorman, Maggie

AU - Thomas, Huw

AU - Peto, Julian

AU - Bishop, Timothy

AU - Gray, Richard

AU - Maher, Eamonn R.

AU - Lucassen, Anneke

AU - Kerr, David

AU - Evans, Gareth R.

AU - van Wezel, Tom

AU - Morreau, Hans

AU - Wijnen, Juul T.

AU - Hopper, John L.

AU - Southey, Melissa C.

AU - Giles, Graham G.

AU - Severi, Gianluca

AU - Castellví-Bel, Sergi

AU - Ruiz-Ponte, Clara

AU - Carracedo, Angel

AU - Castells, Antoni

AU - Försti, Asta

AU - Hemminki, Kari

AU - Vodicka, Pavel

AU - Naccarati, Alessio

AU - Lipton, Lara

AU - Ho, Judy W.C.

AU - Cheng, King Yip

AU - Sham, Pak C.

AU - Luk, J.

AU - Agúndez, Jose A.G.

AU - Ladero, Jose M.

AU - de la Hoya, Miguel

AU - Caldés, Trinidad

AU - Niittymäki, Iina

AU - Tuupanen, Sari

AU - Karhu, Auli

AU - Aaltonen, Lauri A.

AU - Cazier, Jean Baptiste

AU - Tomlinson, Ian P.M.

AU - Houlston, Richard S.

PY - 2008/11/19

Y1 - 2008/11/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=56049119387&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddn267

DO - 10.1093/hmg/ddn267

M3 - Journal article

C2 - 18753146

SN - 0964-6906

VL - 17

SP - 3720

EP - 3727

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 23

ER -

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

Abstract

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