Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
24084763
TITLE
Germline variants and advanced colorectal adenomas: adenoma prevention with celecoxib trial genome-wide association study.
ABSTRACT
PURPOSE NlmCategory: OBJECTIVE
Identification of single-nucleotide polymorphisms (SNP) associated with development of advanced colorectal adenomas.
EXPERIMENTAL DESIGN NlmCategory: METHODS
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 NlmCategory: 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 NlmCategory: 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.
2013 AACR.
DATE PUBLISHED
2013 Dec 1
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2013/10/01
aheadofprint 2013/11/01
entrez 2013/10/03 06:00
pubmed 2013/10/03 06:00
medline 2014/07/16 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Wang J Wang Jiping J Authors' Affiliations: Department of Surgery, Division of Surgical Oncology, Center for Genomic Medicine, Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts; Genome Center and Department of Biochemistry and Molecular Medicine, University of California, Davis, California; Department of Epidemiology and Statistics, Memorial Sloan-Kettering Cancer Center, New York; RIKEN Center for Genomic Medicine, Tokyo, Japan; Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Edinburgh; Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom; Ludwig Colon Cancer Initiative Laboratory, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville; Genetic and Molecular Epidemiology Laboratories, and Familial Cancer laboratory, Queensland Institute of Medical Research, Brisbane; Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia; and Department of Medicine, University of Chicago, Chicago, Illinois.
Carvajal-Carmona LG Carvajal-Carmona Luis G LG
Chu JH Chu Jen-Hwa JH
Zauber AG Zauber Ann G AG
APC Trial Collaborators
Kubo M Kubo Michikai M
Matsuda K Matsuda Koichi K
Dunlop M Dunlop Malcolm M
Houlston RS Houlston Richard S RS
Sieber O Sieber Oliver O
Lipton L Lipton Lara L
Gibbs P Gibbs Peter P
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
Young J Young Joanne J
Baird PN Baird Paul N PN
Ratain MJ Ratain Mark J MJ
Nakamura Y Nakamura Yusuke Y
Weiss ST Weiss Scott T ST
Tomlinson I Tomlinson Ian I
Bertagnolli MM Bertagnolli Monica M MM
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Bertagnolli M M MM
Hawk E T ET
Eagle C J CJ
Zauber A G AG
Kim K M KM
Corle D D
Rosenstein R R
Tang J J
Hess T T
Wilton A A
Anderson W W
Doody L L
Redston M M
Woloj G M GM
Bagheri D D
Crawford A A
Schietrum M M
Ladouceur V V
Rosen S S
Friedman L L
Makuch R R
Phillips R R
Taylor P P
Auerbach S S
Barish C F CF
Barringer T T
Bennetts R W RW
Blitstein M M
Bruggen J J
Salem Winston W
Carricaburu P P
Chung D D
Colizzo F F
Curtis R R
Dewar T T
DuBois R R
Feinstat T T
Foley T R TR
Gabbaizadeh D D
Geenen J J
Giardiello F F
Goetsch A A
Goldberg M M
Goldstein J L JL
Harlan W W
Hogan R R
Kamionkowski M M
Kelfer M M
Kerzner B B
Kim K K
Klimberg I I
Koval G G
Krone C C
Krumholz S S
Layton M W MW
Lightdale C C
Limburg P J PJ
Lind C C
Lipkis D D
Lloyd M M
Maccini D D
MacMillan F F
Madoff R R
Malik A A
Markowitz A A
Marks R R
McDougall C J C
Miner P P
Murphy M M
Namais A A
Nickl N N
Pochapin M M
Monahan Jay J
Pruitt R E RE
Puolos J J
Riff D S DS
Roman R R
Rubin L L
Ruff D D
Safdi M M
Saltzman J J
Salzberg B B
Sattler J A JA
Schleinitz P P
Schwartz J J
Schwartz M M
Silpa M M
Silvers D D
Smoot D D
Sontag S S
Sorrell R J RJ
Stanton D D
Sturgeon J J
Tracey J P JP
Werth T T
Wilcox C M CM
Wohlman R R
Woods S S
Burn J J
Ee H H
Korman M M
Lee A A
Leggett B B
Macrae F F
Mollison L L
Yeomans N N
Young G G
Aumais G G
Bailey R R
Bernstein C C
Cohen L L
Dallaire C C
Dube R R
Morgan D D
Sylwestrowicz T T
Van Rosendaal G G
Van Zantan S J SJ
JOURNAL
VOLUME: 19
ISSUE: 23
TITLE: Clinical cancer research : an official journal of the American Association for Cancer Research
ISOABBREVIATION: Clin. Cancer Res.
YEAR: 2013
MONTH: Dec
DAY: 1
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1078-0432
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Clin Cancer Res
COUNTRY: United States
ISSNLINKING: 1078-0432
NLMUNIQUEID: 9502500
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
#CA-95-011 NCI NIH HHS United States
090532 Wellcome Trust United Kingdom
090532/Z/09/Z Wellcome Trust United Kingdom
12076 Cancer Research UK United Kingdom
CA-N01-95015 NCI NIH HHS United States
G0000657-53203 Medical Research Council United Kingdom
HHSN261201000082C NCI NIH HHS United States
HHSN261201000082C PHS HHS United States
MC_U127527198 Medical Research Council United Kingdom
N01CN95015 NCI NIH HHS United States
NCI N01-95015 PHS HHS United States
P30 CA008748 NCI NIH HHS United States
U01 CA074783 NCI NIH HHS United States
U01 CA074794 NCI NIH HHS United States
U01 CA074799 NCI NIH HHS United States
U01 CA074800 NCI NIH HHS United States
U01 CA097735 NCI NIH HHS United States
U01 CA122839 NCI NIH HHS United States
U01 GM061393 NIGMS NIH HHS United States
U01GM61390 NIGMS NIH HHS United States
U01GM61393 NIGMS NIH HHS United States
U24 CA074783 NCI NIH HHS United States
U24 CA074794 NCI NIH HHS United States
U24 CA074799 NCI NIH HHS United States
U24 CA074800 NCI NIH HHS United States
U24 CA097735 NCI NIH HHS United States
UM1 CA167551 NCI NIH HHS United States
UO1 CA074783 NCI NIH HHS United States
UO1 CA074794 NCI NIH HHS United States
UO1 CA074799 NCI NIH HHS United States
UO1 CA074800 NCI NIH HHS United States
UO1 CA074806 NCI NIH HHS United States
UO1 CA097735 NCI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adenoma prevention & control
Anticarcinogenic Agents therapeutic use
Case-Control Studies therapeutic use
Celecoxib therapeutic use
Colorectal Neoplasms prevention & control
Female prevention & control
Gene-Environment Interaction prevention & control
Genetic Predisposition to Disease prevention & control
Genome-Wide Association Study prevention & control
Germ-Line Mutation prevention & control
Humans prevention & control
Linkage Disequilibrium prevention & control
Male prevention & control
Neoplasm Recurrence, Local prevention & control
Polymorphism, Single Nucleotide prevention & control
Prospective Studies prevention & control
Pyrazoles therapeutic use
Randomized Controlled Trials as Topic therapeutic use
Sulfonamides therapeutic use
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Anticarcinogenic Agents
0 Pyrazoles
0 Sulfonamides
JCX84Q7J1L Celecoxib
OTHER ID's
OTHERID SOURCE
NIHMS588437 NLM
PMC4037290 NLM