A novel colorectal cancer risk locus at 4q32.2 identified from an international genome-wide association study

Stephanie L. Schmit, Fredrick R. Schumacher, Christopher K. Edlund, David V. Conti, Leon Raskin, Flavio Lejbkowicz, Mila Pinchev, Hedy S. Rennert, Mark A. Jenkins, John L. Hopper, Daniel D. Buchanan, Noralane Morey Lindor, Loic Le Marchand, Steven Gallinger, Robert W. Haile, Polly A. Newcomb, Shu Chen Huang, Gad Rennert, Graham Casey, Stephen B. Gruber

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Abstract

Only a fraction of colorectal cancer heritability is explained by known risk-conferring genetic variation. This study was designed to identify novel risk alleles in Europeans. We conducted a genome-wide association study (GWAS) meta-analysis of colorectal cancer in participants from a population-based case-control study in Israel (n = 1616 cases, 1329 controls) and a consortium study from the Colon Cancer Family Registry (n = 1977 cases, 999 controls). We used a two-stage (discovery-replication) GWAS design, followed by a joint meta-analysis. A combined analysis identified a novel susceptibility locus that reached genome-wide significance on chromosome 4q32.2 [rs35509282, risk allele = A (minor allele frequency = 0.09); odds ratio (OR) per risk allele = 1.53; P value = 8.2 × 10(-9); nearest gene = FSTL5]. The direction of the association was consistent across studies. In addition, we confirmed that 14 of 29 previously identified susceptibility variants were significantly associated with risk of colorectal cancer in this study. Genetic variation on chromosome 4q32.2 is significantly associated with risk of colorectal cancer in Ashkenazi Jews and Europeans in this study.

Original languageEnglish (US)
Pages (from-to)2512-2519
Number of pages8
JournalCarcinogenesis
Volume35
Issue number11
DOIs
StatePublished - Nov 1 2014

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Genome-Wide Association Study
Colorectal Neoplasms
Alleles
Meta-Analysis
Chromosomes
Jews
Israel
Gene Frequency
Colonic Neoplasms
Registries
Case-Control Studies
Joints
Odds Ratio
Genome
Population
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Schmit, S. L., Schumacher, F. R., Edlund, C. K., Conti, D. V., Raskin, L., Lejbkowicz, F., ... Gruber, S. B. (2014). A novel colorectal cancer risk locus at 4q32.2 identified from an international genome-wide association study. Carcinogenesis, 35(11), 2512-2519. https://doi.org/10.1093/carcin/bgu148

A novel colorectal cancer risk locus at 4q32.2 identified from an international genome-wide association study. / Schmit, Stephanie L.; Schumacher, Fredrick R.; Edlund, Christopher K.; Conti, David V.; Raskin, Leon; Lejbkowicz, Flavio; Pinchev, Mila; Rennert, Hedy S.; Jenkins, Mark A.; Hopper, John L.; Buchanan, Daniel D.; Lindor, Noralane Morey; Le Marchand, Loic; Gallinger, Steven; Haile, Robert W.; Newcomb, Polly A.; Huang, Shu Chen; Rennert, Gad; Casey, Graham; Gruber, Stephen B.

In: Carcinogenesis, Vol. 35, No. 11, 01.11.2014, p. 2512-2519.

Research output: Contribution to journalArticle

Schmit, SL, Schumacher, FR, Edlund, CK, Conti, DV, Raskin, L, Lejbkowicz, F, Pinchev, M, Rennert, HS, Jenkins, MA, Hopper, JL, Buchanan, DD, Lindor, NM, Le Marchand, L, Gallinger, S, Haile, RW, Newcomb, PA, Huang, SC, Rennert, G, Casey, G & Gruber, SB 2014, 'A novel colorectal cancer risk locus at 4q32.2 identified from an international genome-wide association study', Carcinogenesis, vol. 35, no. 11, pp. 2512-2519. https://doi.org/10.1093/carcin/bgu148
Schmit SL, Schumacher FR, Edlund CK, Conti DV, Raskin L, Lejbkowicz F et al. A novel colorectal cancer risk locus at 4q32.2 identified from an international genome-wide association study. Carcinogenesis. 2014 Nov 1;35(11):2512-2519. https://doi.org/10.1093/carcin/bgu148
Schmit, Stephanie L. ; Schumacher, Fredrick R. ; Edlund, Christopher K. ; Conti, David V. ; Raskin, Leon ; Lejbkowicz, Flavio ; Pinchev, Mila ; Rennert, Hedy S. ; Jenkins, Mark A. ; Hopper, John L. ; Buchanan, Daniel D. ; Lindor, Noralane Morey ; Le Marchand, Loic ; Gallinger, Steven ; Haile, Robert W. ; Newcomb, Polly A. ; Huang, Shu Chen ; Rennert, Gad ; Casey, Graham ; Gruber, Stephen B. / A novel colorectal cancer risk locus at 4q32.2 identified from an international genome-wide association study. In: Carcinogenesis. 2014 ; Vol. 35, No. 11. pp. 2512-2519.
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