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Meta-Analysis
. 2013 Dec 1;19(23):6430-7.
doi: 10.1158/1078-0432.CCR-13-0550. Epub 2013 Oct 1.

Germline variants and advanced colorectal adenomas: adenoma prevention with celecoxib trial genome-wide association study

Jiping Wang  1 , Luis G Carvajal-Carmona, Jen-Hwa Chu, Ann G Zauber; APC Trial Collaborators; Michikai Kubo, Koichi Matsuda, Malcolm Dunlop, Richard S Houlston, Oliver Sieber, Lara Lipton, Peter Gibbs, Nicholas G Martin, Grant W Montgomery, Joanne Young, Paul N Baird, Mark J Ratain, Yusuke Nakamura, Scott T Weiss, Ian Tomlinson, Monica M Bertagnolli
Collaborators, Affiliations
Meta-Analysis

Germline variants and advanced colorectal adenomas: adenoma prevention with celecoxib trial genome-wide association study

Jiping Wang et al. Clin Cancer Res. .

Abstract

Purpose: Identification of single-nucleotide polymorphisms (SNP) associated with development of advanced colorectal adenomas.

Experimental design: Discovery phase: 1,406 Caucasian patients (139 advanced adenoma cases and 1,267 controls) from the Adenoma Prevention with Celecoxib (APC) trial were included in a genome-wide association study (GWAS) to identify variants associated with postpolypectomy disease recurrence. Genome-wide significance was defined as false discovery rate less than 0.05, unadjusted P = 7.4 × 10(-7). Validation phase: results were further evaluated using 4,175 familial colorectal adenoma cases and 5,036 controls from patients of European ancestry [COloRectal Gene Identification consortium (CORGI), Scotland, Australia, and VQ58].

Results: Our study identified eight SNPs associated with advanced-adenoma risk in the APC trial (rs2837156, rs7278863, rs2837237, rs2837241, rs2837254, rs741864 at 21q22.2, and rs1381392 and rs17651822 at 3p24.1, at P < 10(-7) level with OR > 2). Five variants in strong pairwise linkage disequilibrium (rs7278863, rs2837237, rs741864, rs741864, and rs2837241; r(2) = 0.8-1) are in or near the coding region for the tight junction adhesion protein, IGSF5. An additional variant associated with advanced adenomas, rs1535989 [minor allele frequency, 0.11; OR, 2.09; 95% confidence interval (CI), 1.50-2.91], also predicted colorectal cancer development in a validation analysis (P = 0.019) using a series of adenoma cases or colorectal cancer (CORGI study) and 3 sets of colorectal cancer cases and controls (Scotland, VQ58, and Australia; N = 9,211).

Conclusions: Our results suggest that common polymorphisms contribute to the risk of developing advanced adenomas and might also contribute to the risk of developing colorectal cancer. The variant at rs1535989 may identify patients whose risk for neoplasia warrants increased colonoscopic surveillance.

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Figures

Figure 1
Figure 1
AA: advanced adenoma *Including subjects with familial adenoma from CORGI
Figure 2
Figure 2
The 6 IGSF-5 related SNPs are within very tight LD region
See this image and copyright information in PMC

References

    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29. - PubMed
    1. Zauber AG, Winawer SJ, O'Brien MJ, Lansdorp-Vogelaar I, van Ballegooijen M, Hankey BF, et al. Colonoscopic polypectomy and long-term prevention of colorectal cancer deaths. New Engl J Med. 2012;366:687–96. - PMC - PubMed
    1. Saini SD, Kim HM, Schoenfeld P. Incidence of advanced adenomas at surveillance colonoscopy in patients with a personal history of colon adenomas: a meta-analysis and systematic review. Gastrointest Endosc. 2006;64:614–26. - PubMed
    1. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006;355:873–84. - PubMed
    1. Carvajal-Carmona LG, Cazier J-B, Jones AM, Howarth K, Broderick P, Pittman A, et al. Fine-mapping of colorectal cancer susceptibility loci at 8q23.3, 16q22.1 and 19q13.11: refinement of association signals and use of in silico analysis to suggest functional variation and unexpected candidate target genes. Human Molecular Genetics. 2011;20:2879–88. - PMC - PubMed

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