Meta-analysis of new genome-wide association studies of colorectal cancer risk

Ulrike Peters, Carolyn M. Hutter, Li Hsu, Fredrick R. Schumacher, David V. Conti, Christopher S. Carlson, Christopher K. Edlund, Robert W. Haile, Steven Gallinger, Brent W. Zanke, Mathieu Lemire, Jagadish Rangrej, Raakhee Vijayaraghavan, Andrew T. Chan, Aditi Hazra, David J. Hunter, Jing Ma, Charles S. Fuchs, Edward L. Giovannucci, Peter Kraft & 38 others Yan Liu, Lin Chen, Shuo Jiao, Karen W. Makar, Darin Taverna, Stephen B. Gruber, Gad Rennert, Victor Moreno, Cornelia M. Ulrich, Michael O. Woods, Roger C. Green, Patrick S. Parfrey, Ross L. Prentice, Charles Kooperberg, Rebecca D. Jackson, Andrea Z. Lacroix, Bette J. Caan, Richard B. Hayes, Sonja I. Berndt, Stephen J. Chanock, Robert E. Schoen, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Bernd Frank, Stéphane Bézieau, Sébastien Küry, Martha L. Slattery, John L. Hopper, Mark A. Jenkins, Loic Le Marchand, Noralane Morey Lindor, Polly A. Newcomb, Daniela Seminara, Thomas J. Hudson, David J. Duggan, John D. Potter, Graham Casey

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 × 10-8). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 × 10-5). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 × 10 -4). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.

Original languageEnglish (US)
Pages (from-to)217-234
Number of pages18
JournalHuman Genetics
Volume131
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Genome-Wide Association Study
Meta-Analysis
Colorectal Neoplasms
Single Nucleotide Polymorphism
Developed Countries
Cause of Death
Neoplasms
Odds Ratio
Genome
Confidence Intervals
Genes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Peters, U., Hutter, C. M., Hsu, L., Schumacher, F. R., Conti, D. V., Carlson, C. S., ... Casey, G. (2012). Meta-analysis of new genome-wide association studies of colorectal cancer risk. Human Genetics, 131(2), 217-234. https://doi.org/10.1007/s00439-011-1055-0

Meta-analysis of new genome-wide association studies of colorectal cancer risk. / Peters, Ulrike; Hutter, Carolyn M.; Hsu, Li; Schumacher, Fredrick R.; Conti, David V.; Carlson, Christopher S.; Edlund, Christopher K.; Haile, Robert W.; Gallinger, Steven; Zanke, Brent W.; Lemire, Mathieu; Rangrej, Jagadish; Vijayaraghavan, Raakhee; Chan, Andrew T.; Hazra, Aditi; Hunter, David J.; Ma, Jing; Fuchs, Charles S.; Giovannucci, Edward L.; Kraft, Peter; Liu, Yan; Chen, Lin; Jiao, Shuo; Makar, Karen W.; Taverna, Darin; Gruber, Stephen B.; Rennert, Gad; Moreno, Victor; Ulrich, Cornelia M.; Woods, Michael O.; Green, Roger C.; Parfrey, Patrick S.; Prentice, Ross L.; Kooperberg, Charles; Jackson, Rebecca D.; Lacroix, Andrea Z.; Caan, Bette J.; Hayes, Richard B.; Berndt, Sonja I.; Chanock, Stephen J.; Schoen, Robert E.; Chang-Claude, Jenny; Hoffmeister, Michael; Brenner, Hermann; Frank, Bernd; Bézieau, Stéphane; Küry, Sébastien; Slattery, Martha L.; Hopper, John L.; Jenkins, Mark A.; Le Marchand, Loic; Lindor, Noralane Morey; Newcomb, Polly A.; Seminara, Daniela; Hudson, Thomas J.; Duggan, David J.; Potter, John D.; Casey, Graham.

In: Human Genetics, Vol. 131, No. 2, 02.2012, p. 217-234.

Research output: Contribution to journalArticle

Peters, U, Hutter, CM, Hsu, L, Schumacher, FR, Conti, DV, Carlson, CS, Edlund, CK, Haile, RW, Gallinger, S, Zanke, BW, Lemire, M, Rangrej, J, Vijayaraghavan, R, Chan, AT, Hazra, A, Hunter, DJ, Ma, J, Fuchs, CS, Giovannucci, EL, Kraft, P, Liu, Y, Chen, L, Jiao, S, Makar, KW, Taverna, D, Gruber, SB, Rennert, G, Moreno, V, Ulrich, CM, Woods, MO, Green, RC, Parfrey, PS, Prentice, RL, Kooperberg, C, Jackson, RD, Lacroix, AZ, Caan, BJ, Hayes, RB, Berndt, SI, Chanock, SJ, Schoen, RE, Chang-Claude, J, Hoffmeister, M, Brenner, H, Frank, B, Bézieau, S, Küry, S, Slattery, ML, Hopper, JL, Jenkins, MA, Le Marchand, L, Lindor, NM, Newcomb, PA, Seminara, D, Hudson, TJ, Duggan, DJ, Potter, JD & Casey, G 2012, 'Meta-analysis of new genome-wide association studies of colorectal cancer risk', Human Genetics, vol. 131, no. 2, pp. 217-234. https://doi.org/10.1007/s00439-011-1055-0
Peters U, Hutter CM, Hsu L, Schumacher FR, Conti DV, Carlson CS et al. Meta-analysis of new genome-wide association studies of colorectal cancer risk. Human Genetics. 2012 Feb;131(2):217-234. https://doi.org/10.1007/s00439-011-1055-0
Peters, Ulrike ; Hutter, Carolyn M. ; Hsu, Li ; Schumacher, Fredrick R. ; Conti, David V. ; Carlson, Christopher S. ; Edlund, Christopher K. ; Haile, Robert W. ; Gallinger, Steven ; Zanke, Brent W. ; Lemire, Mathieu ; Rangrej, Jagadish ; Vijayaraghavan, Raakhee ; Chan, Andrew T. ; Hazra, Aditi ; Hunter, David J. ; Ma, Jing ; Fuchs, Charles S. ; Giovannucci, Edward L. ; Kraft, Peter ; Liu, Yan ; Chen, Lin ; Jiao, Shuo ; Makar, Karen W. ; Taverna, Darin ; Gruber, Stephen B. ; Rennert, Gad ; Moreno, Victor ; Ulrich, Cornelia M. ; Woods, Michael O. ; Green, Roger C. ; Parfrey, Patrick S. ; Prentice, Ross L. ; Kooperberg, Charles ; Jackson, Rebecca D. ; Lacroix, Andrea Z. ; Caan, Bette J. ; Hayes, Richard B. ; Berndt, Sonja I. ; Chanock, Stephen J. ; Schoen, Robert E. ; Chang-Claude, Jenny ; Hoffmeister, Michael ; Brenner, Hermann ; Frank, Bernd ; Bézieau, Stéphane ; Küry, Sébastien ; Slattery, Martha L. ; Hopper, John L. ; Jenkins, Mark A. ; Le Marchand, Loic ; Lindor, Noralane Morey ; Newcomb, Polly A. ; Seminara, Daniela ; Hudson, Thomas J. ; Duggan, David J. ; Potter, John D. ; Casey, Graham. / Meta-analysis of new genome-wide association studies of colorectal cancer risk. In: Human Genetics. 2012 ; Vol. 131, No. 2. pp. 217-234.
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abstract = "Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95{\%} confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 × 10-8). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 × 10-5). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 × 10 -4). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.",
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AU - Peters, Ulrike

AU - Hutter, Carolyn M.

AU - Hsu, Li

AU - Schumacher, Fredrick R.

AU - Conti, David V.

AU - Carlson, Christopher S.

AU - Edlund, Christopher K.

AU - Haile, Robert W.

AU - Gallinger, Steven

AU - Zanke, Brent W.

AU - Lemire, Mathieu

AU - Rangrej, Jagadish

AU - Vijayaraghavan, Raakhee

AU - Chan, Andrew T.

AU - Hazra, Aditi

AU - Hunter, David J.

AU - Ma, Jing

AU - Fuchs, Charles S.

AU - Giovannucci, Edward L.

AU - Kraft, Peter

AU - Liu, Yan

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AU - Jiao, Shuo

AU - Makar, Karen W.

AU - Taverna, Darin

AU - Gruber, Stephen B.

AU - Rennert, Gad

AU - Moreno, Victor

AU - Ulrich, Cornelia M.

AU - Woods, Michael O.

AU - Green, Roger C.

AU - Parfrey, Patrick S.

AU - Prentice, Ross L.

AU - Kooperberg, Charles

AU - Jackson, Rebecca D.

AU - Lacroix, Andrea Z.

AU - Caan, Bette J.

AU - Hayes, Richard B.

AU - Berndt, Sonja I.

AU - Chanock, Stephen J.

AU - Schoen, Robert E.

AU - Chang-Claude, Jenny

AU - Hoffmeister, Michael

AU - Brenner, Hermann

AU - Frank, Bernd

AU - Bézieau, Stéphane

AU - Küry, Sébastien

AU - Slattery, Martha L.

AU - Hopper, John L.

AU - Jenkins, Mark A.

AU - Le Marchand, Loic

AU - Lindor, Noralane Morey

AU - Newcomb, Polly A.

AU - Seminara, Daniela

AU - Hudson, Thomas J.

AU - Duggan, David J.

AU - Potter, John D.

AU - Casey, Graham

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