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Identification of genetic susceptibility loci for colorectal tumors in a genome-wide meta-analysis

Authors
 Ulrike Peters  ;  Shuo Jiao  ;  Fredrick R. Schumacher  ;  Carolyn M. Hutter  ;  Aaron K. Aragaki  ;  John A. Baron  ;  Sonja I. Berndt  ;  Stéphane Bézieau  ;  Hermann Brenner  ;  Katja Butterbach  ;  Bette J. Caan  ;  Peter T. Campbell  ;  Christopher S. Carlson  ;  Graham Casey  ;  Andrew T. Chan  ;  Jenny Chang-Claude  ;  Stephen J. Chanock  ;  Lin S. Chen  ;  Gerhard A. Coetzee  ;  Simon G. Coetzee  ;  David V. Conti  ;  Keith R. Curtis  ;  David Duggan  ;  Todd Edwards  ;  Charles S. Fuchs  ;  Steven Gallinger  ;  Edward L. Giovannucci  ;  Stephanie M. Gogarten  ;  Stephen B. Gruber  ;  Robert W. Haile  ;  Tabitha A. Harrison  ;  Richard B. Hayes  ;  Brian E. Henderson  ;  Michael Hoffmeister  ;  John L. Hopper  ;  Thomas J. Hudson  ;  David J. Hunter  ;  Rebecca D. Jackson  ;  Sun Ha Jee  ;  Mark A. Jenkins  ;  Wei-Hua Jia  ;  Laurence N. Kolonel  ;  Charles Kooperberg  ;  Sébastien Küry  ;  Andrea Z. Lacroix  ;  Cathy C. Laurie  ;  Cecelia A. Laurie  ;  Loic Le Marchand  ;  Mathieu Lemire  ;  David Levine  ;  Noralane M. Lindor  ;  Yan Liu  ;  Jing Ma  ;  Karen W. Makar  ;  Keitaro Matsuo  ;  Polly A. Newcomb  ;  John D. Potter  ;  Ross L. Prentice  ;  Conghui Qu  ;  Thomas Rohan  ;  Stephanie A. Rosse  ;  Robert E. Schoen  ;  Daniela Seminara  ;  Martha Shrubsole  ;  Xiao-Ou Shu  ;  Martha L. Slattery  ;  Darin Taverna  ;  Stephen N. Thibodeau  ;  Cornelia M. Ulrich  ;  Emily White  ;  Yongbing Xiang  ;  Brent W. Zanke  ;  Yi-Xin Zeng  ;  Ben Zhang  ;  Wei Zheng  ;  Li Hsu 
Citation
 GASTROENTEROLOGY, Vol.144(4) : 799-807, 2013 
Journal Title
GASTROENTEROLOGY
ISSN
 0016-5085 
Issue Date
2013
MeSH
Age Distribution ; Aged ; Aged, 80 and over ; Colorectal Neoplasms/epidemiology ; Colorectal Neoplasms/genetics* ; Cyclin D2/genetics* ; DNA-Binding Proteins/genetics ; Female ; Genetic Loci/genetics* ; Genetic Predisposition to Disease/epidemiology* ; Genome-Wide Association Study ; Humans ; Incidence ; Laminin/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Prognosis ; Risk Assessment ; Sex Distribution ; T-Box Domain Proteins/genetics
Keywords
Colon Cancer ; Genetics ; Risk Factors ; SNP
Abstract
BACKGROUND & AIMS:
Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis.
METHODS:
We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent.
RESULTS:
Based on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 × 10(-8): an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 × 10(-8)). We also found evidence for 3 additional loci with P values less than 5.0 × 10(-7): a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 × 10(-8)), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 × 10(-8)), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 × 10(-7)).
CONCLUSIONS:
In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to β-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation.
Files in This Item:
T201302137.pdf Download
DOI
10.1053/j.gastro.2012.12.020
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87187
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