A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1

Mathieu Lemire, Conghui Qu, Lenora W M Loo, Syed H E Zaidi, Hansong Wang, Sonja I. Berndt, Stéphane Bézieau, Hermann Brenner, Peter T. Campbell, Andrew T. Chan, Jenny Chang-Claude, Mengmeng Du, Christopher K. Edlund, Steven Gallinger, Robert W. Haile, Tabitha A. Harrison, Michael Hoffmeister, John L. Hopper, Lifang Hou, Li HsuEric J. Jacobs, Mark A. Jenkins, Jihyoun Jeon, Sébastien Küry, Li Li, Noralane Morey Lindor, Polly A. Newcomb, John D. Potter, Gad Rennert, Anja Rudolph, Robert E. Schoen, Fredrick R. Schumacher, Daniela Seminara, Gianluca Severi, Martha L. Slattery, Emily White, Michael O. Woods, Michelle Cotterchio, Loïc Le Marchand, Graham Casey, Stephen B. Gruber, Ulrike Peters, Thomas J. Hudson

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Over 50 loci associated with colorectal cancer (CRC) have been uncovered by genome-wide association studies (GWAS). Identifying additional loci has the potential to help elucidate aspects of the underlying biological processes leading to better understanding of the pathogenesis of the disease. We re-evaluated a GWAS by excluding controls that have family history of CRC or personal history of colorectal polyps, as we hypothesized that their inclusion reduces power to detect associations. This is supported empirically and through simulations. Two-phase GWAS analysis was performed in a total of 16,517 cases and 14,487 controls. We identified rs17094983, a SNP associated with risk of CRC [p = 2.5 × 10−10; odds ratio estimated by re-including all controls (OR) = 0.87, 95 % confidence interval (CI) 0.83–0.91; minor allele frequency (MAF) = 13 %]. Results were replicated in samples of African descent (1894 cases and 4703 controls; p = 0.01; OR = 0.86, 95 % CI 0.77–0.97; MAF = 16 %). Gene expression data in 195 colon adenocarcinomas and 59 normal colon tissues from two different studies revealed that this locus has genotypes that are associated with RTN1 (Reticulon 1) expression (p = 0.001), a protein-coding gene involved in survival and proliferation of cancer cells which is highly expressed in normal colon tissues but has significantly reduced expression in tumor cells (p = 1.3 × 10−8).

Original languageEnglish (US)
Pages (from-to)1249-1262
Number of pages14
JournalHuman Genetics
Volume134
Issue number11-12
DOIs
StatePublished - Sep 24 2015

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Genome-Wide Association Study
Colorectal Neoplasms
Colon
Gene Frequency
Confidence Intervals
Biological Phenomena
Polyps
Single Nucleotide Polymorphism
Neoplasms
Adenocarcinoma
Odds Ratio
Genotype
Cell Proliferation
Gene Expression
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Lemire, M., Qu, C., Loo, L. W. M., Zaidi, S. H. E., Wang, H., Berndt, S. I., ... Hudson, T. J. (2015). A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1. Human Genetics, 134(11-12), 1249-1262. https://doi.org/10.1007/s00439-015-1598-6

A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1. / Lemire, Mathieu; Qu, Conghui; Loo, Lenora W M; Zaidi, Syed H E; Wang, Hansong; Berndt, Sonja I.; Bézieau, Stéphane; Brenner, Hermann; Campbell, Peter T.; Chan, Andrew T.; Chang-Claude, Jenny; Du, Mengmeng; Edlund, Christopher K.; Gallinger, Steven; Haile, Robert W.; Harrison, Tabitha A.; Hoffmeister, Michael; Hopper, John L.; Hou, Lifang; Hsu, Li; Jacobs, Eric J.; Jenkins, Mark A.; Jeon, Jihyoun; Küry, Sébastien; Li, Li; Lindor, Noralane Morey; Newcomb, Polly A.; Potter, John D.; Rennert, Gad; Rudolph, Anja; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Severi, Gianluca; Slattery, Martha L.; White, Emily; Woods, Michael O.; Cotterchio, Michelle; Le Marchand, Loïc; Casey, Graham; Gruber, Stephen B.; Peters, Ulrike; Hudson, Thomas J.

In: Human Genetics, Vol. 134, No. 11-12, 24.09.2015, p. 1249-1262.

Research output: Contribution to journalArticle

Lemire, M, Qu, C, Loo, LWM, Zaidi, SHE, Wang, H, Berndt, SI, Bézieau, S, Brenner, H, Campbell, PT, Chan, AT, Chang-Claude, J, Du, M, Edlund, CK, Gallinger, S, Haile, RW, Harrison, TA, Hoffmeister, M, Hopper, JL, Hou, L, Hsu, L, Jacobs, EJ, Jenkins, MA, Jeon, J, Küry, S, Li, L, Lindor, NM, Newcomb, PA, Potter, JD, Rennert, G, Rudolph, A, Schoen, RE, Schumacher, FR, Seminara, D, Severi, G, Slattery, ML, White, E, Woods, MO, Cotterchio, M, Le Marchand, L, Casey, G, Gruber, SB, Peters, U & Hudson, TJ 2015, 'A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1', Human Genetics, vol. 134, no. 11-12, pp. 1249-1262. https://doi.org/10.1007/s00439-015-1598-6
Lemire M, Qu C, Loo LWM, Zaidi SHE, Wang H, Berndt SI et al. A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1. Human Genetics. 2015 Sep 24;134(11-12):1249-1262. https://doi.org/10.1007/s00439-015-1598-6
Lemire, Mathieu ; Qu, Conghui ; Loo, Lenora W M ; Zaidi, Syed H E ; Wang, Hansong ; Berndt, Sonja I. ; Bézieau, Stéphane ; Brenner, Hermann ; Campbell, Peter T. ; Chan, Andrew T. ; Chang-Claude, Jenny ; Du, Mengmeng ; Edlund, Christopher K. ; Gallinger, Steven ; Haile, Robert W. ; Harrison, Tabitha A. ; Hoffmeister, Michael ; Hopper, John L. ; Hou, Lifang ; Hsu, Li ; Jacobs, Eric J. ; Jenkins, Mark A. ; Jeon, Jihyoun ; Küry, Sébastien ; Li, Li ; Lindor, Noralane Morey ; Newcomb, Polly A. ; Potter, John D. ; Rennert, Gad ; Rudolph, Anja ; Schoen, Robert E. ; Schumacher, Fredrick R. ; Seminara, Daniela ; Severi, Gianluca ; Slattery, Martha L. ; White, Emily ; Woods, Michael O. ; Cotterchio, Michelle ; Le Marchand, Loïc ; Casey, Graham ; Gruber, Stephen B. ; Peters, Ulrike ; Hudson, Thomas J. / A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1. In: Human Genetics. 2015 ; Vol. 134, No. 11-12. pp. 1249-1262.
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abstract = "Over 50 loci associated with colorectal cancer (CRC) have been uncovered by genome-wide association studies (GWAS). Identifying additional loci has the potential to help elucidate aspects of the underlying biological processes leading to better understanding of the pathogenesis of the disease. We re-evaluated a GWAS by excluding controls that have family history of CRC or personal history of colorectal polyps, as we hypothesized that their inclusion reduces power to detect associations. This is supported empirically and through simulations. Two-phase GWAS analysis was performed in a total of 16,517 cases and 14,487 controls. We identified rs17094983, a SNP associated with risk of CRC [p = 2.5 × 10−10; odds ratio estimated by re-including all controls (OR) = 0.87, 95 {\%} confidence interval (CI) 0.83–0.91; minor allele frequency (MAF) = 13 {\%}]. Results were replicated in samples of African descent (1894 cases and 4703 controls; p = 0.01; OR = 0.86, 95 {\%} CI 0.77–0.97; MAF = 16 {\%}). Gene expression data in 195 colon adenocarcinomas and 59 normal colon tissues from two different studies revealed that this locus has genotypes that are associated with RTN1 (Reticulon 1) expression (p = 0.001), a protein-coding gene involved in survival and proliferation of cancer cells which is highly expressed in normal colon tissues but has significantly reduced expression in tumor cells (p = 1.3 × 10−8).",
author = "Mathieu Lemire and Conghui Qu and Loo, {Lenora W M} and Zaidi, {Syed H E} and Hansong Wang and Berndt, {Sonja I.} and St{\'e}phane B{\'e}zieau and Hermann Brenner and Campbell, {Peter T.} and Chan, {Andrew T.} and Jenny Chang-Claude and Mengmeng Du and Edlund, {Christopher K.} and Steven Gallinger and Haile, {Robert W.} and Harrison, {Tabitha A.} and Michael Hoffmeister and Hopper, {John L.} and Lifang Hou and Li Hsu and Jacobs, {Eric J.} and Jenkins, {Mark A.} and Jihyoun Jeon and S{\'e}bastien K{\"u}ry and Li Li and Lindor, {Noralane Morey} and Newcomb, {Polly A.} and Potter, {John D.} and Gad Rennert and Anja Rudolph and Schoen, {Robert E.} and Schumacher, {Fredrick R.} and Daniela Seminara and Gianluca Severi and Slattery, {Martha L.} and Emily White and Woods, {Michael O.} and Michelle Cotterchio and {Le Marchand}, Lo{\"i}c and Graham Casey and Gruber, {Stephen B.} and Ulrike Peters and Hudson, {Thomas J.}",
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AU - Lemire, Mathieu

AU - Qu, Conghui

AU - Loo, Lenora W M

AU - Zaidi, Syed H E

AU - Wang, Hansong

AU - Berndt, Sonja I.

AU - Bézieau, Stéphane

AU - Brenner, Hermann

AU - Campbell, Peter T.

AU - Chan, Andrew T.

AU - Chang-Claude, Jenny

AU - Du, Mengmeng

AU - Edlund, Christopher K.

AU - Gallinger, Steven

AU - Haile, Robert W.

AU - Harrison, Tabitha A.

AU - Hoffmeister, Michael

AU - Hopper, John L.

AU - Hou, Lifang

AU - Hsu, Li

AU - Jacobs, Eric J.

AU - Jenkins, Mark A.

AU - Jeon, Jihyoun

AU - Küry, Sébastien

AU - Li, Li

AU - Lindor, Noralane Morey

AU - Newcomb, Polly A.

AU - Potter, John D.

AU - Rennert, Gad

AU - Rudolph, Anja

AU - Schoen, Robert E.

AU - Schumacher, Fredrick R.

AU - Seminara, Daniela

AU - Severi, Gianluca

AU - Slattery, Martha L.

AU - White, Emily

AU - Woods, Michael O.

AU - Cotterchio, Michelle

AU - Le Marchand, Loïc

AU - Casey, Graham

AU - Gruber, Stephen B.

AU - Peters, Ulrike

AU - Hudson, Thomas J.

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