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PMID |
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TITLE |
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Germline variants and advanced colorectal adenomas: adenoma prevention with celecoxib trial genome-wide association study. |
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ABSTRACT |
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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. |
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DATE PUBLISHED |
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HISTORY |
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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 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Wang J |
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Wang |
Jiping |
J |
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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 |
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Carvajal-Carmona |
Luis G |
LG |
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Chu JH |
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Chu |
Jen-Hwa |
JH |
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Zauber AG |
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Zauber |
Ann G |
AG |
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APC Trial Collaborators |
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Kubo M |
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Kubo |
Michikai |
M |
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Matsuda K |
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Matsuda |
Koichi |
K |
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Dunlop M |
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Dunlop |
Malcolm |
M |
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Houlston RS |
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Houlston |
Richard S |
RS |
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Sieber O |
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Sieber |
Oliver |
O |
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Lipton L |
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Lipton |
Lara |
L |
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Gibbs P |
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Gibbs |
Peter |
P |
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Martin NG |
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Martin |
Nicholas G |
NG |
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Montgomery GW |
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Montgomery |
Grant W |
GW |
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Young J |
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Young |
Joanne |
J |
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Baird PN |
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Baird |
Paul N |
PN |
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Ratain MJ |
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Ratain |
Mark J |
MJ |
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Nakamura Y |
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Nakamura |
Yusuke |
Y |
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Weiss ST |
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Weiss |
Scott T |
ST |
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Tomlinson I |
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Tomlinson |
Ian |
I |
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Bertagnolli MM |
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Bertagnolli |
Monica M |
MM |
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INVESTIGATORS |
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LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
Bertagnolli |
M M |
MM |
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Hawk |
E T |
ET |
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Eagle |
C J |
CJ |
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Zauber |
A G |
AG |
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Kim |
K M |
KM |
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Corle |
D |
D |
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Rosenstein |
R |
R |
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Tang |
J |
J |
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Hess |
T |
T |
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Wilton |
A |
A |
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Anderson |
W |
W |
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Doody |
L |
L |
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Redston |
M |
M |
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Woloj |
G M |
GM |
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Bagheri |
D |
D |
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Crawford |
A |
A |
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Schietrum |
M |
M |
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Ladouceur |
V |
V |
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Rosen |
S |
S |
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Friedman |
L |
L |
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Makuch |
R |
R |
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Phillips |
R |
R |
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Taylor |
P |
P |
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Auerbach |
S |
S |
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Barish |
C F |
CF |
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Barringer |
T |
T |
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Bennetts |
R W |
RW |
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Blitstein |
M |
M |
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Bruggen |
J |
J |
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Salem |
Winston |
W |
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Carricaburu |
P |
P |
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Chung |
D |
D |
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Colizzo |
F |
F |
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Curtis |
R |
R |
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Dewar |
T |
T |
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DuBois |
R |
R |
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Feinstat |
T |
T |
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Foley |
T R |
TR |
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Gabbaizadeh |
D |
D |
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Geenen |
J |
J |
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Giardiello |
F |
F |
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Goetsch |
A |
A |
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Goldberg |
M |
M |
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Goldstein |
J L |
JL |
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Harlan |
W |
W |
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Hogan |
R |
R |
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Kamionkowski |
M |
M |
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Kelfer |
M |
M |
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Kerzner |
B |
B |
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Kim |
K |
K |
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Klimberg |
I |
I |
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Koval |
G |
G |
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Krone |
C |
C |
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Krumholz |
S |
S |
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Layton |
M W |
MW |
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Lightdale |
C |
C |
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Limburg |
P J |
PJ |
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Lind |
C |
C |
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Lipkis |
D |
D |
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Lloyd |
M |
M |
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Maccini |
D |
D |
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MacMillan |
F |
F |
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Madoff |
R |
R |
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Malik |
A |
A |
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Markowitz |
A |
A |
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Marks |
R |
R |
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McDougall |
C J |
C |
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Miner |
P |
P |
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Murphy |
M |
M |
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Namais |
A |
A |
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Nickl |
N |
N |
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Pochapin |
M |
M |
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Monahan |
Jay |
J |
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Pruitt |
R E |
RE |
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Puolos |
J |
J |
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Riff |
D S |
DS |
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Roman |
R |
R |
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Rubin |
L |
L |
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Ruff |
D |
D |
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Safdi |
M |
M |
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Saltzman |
J |
J |
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Salzberg |
B |
B |
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Sattler |
J A |
JA |
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Schleinitz |
P |
P |
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Schwartz |
J |
J |
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Schwartz |
M |
M |
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Silpa |
M |
M |
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Silvers |
D |
D |
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Smoot |
D |
D |
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Sontag |
S |
S |
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Sorrell |
R J |
RJ |
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Stanton |
D |
D |
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Sturgeon |
J |
J |
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Tracey |
J P |
JP |
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Werth |
T |
T |
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Wilcox |
C M |
CM |
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Wohlman |
R |
R |
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Woods |
S |
S |
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Burn |
J |
J |
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Ee |
H |
H |
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Korman |
M |
M |
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Lee |
A |
A |
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Leggett |
B |
B |
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Macrae |
F |
F |
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Mollison |
L |
L |
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Yeomans |
N |
N |
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Young |
G |
G |
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Aumais |
G |
G |
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Bailey |
R |
R |
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Bernstein |
C |
C |
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Cohen |
L |
L |
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Dallaire |
C |
C |
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Dube |
R |
R |
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Morgan |
D |
D |
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Sylwestrowicz |
T |
T |
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Van Rosendaal |
G |
G |
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Van Zantan |
S J |
SJ |
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JOURNAL |
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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 |
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MEDLINE JOURNAL |
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MEDLINETA: Clin Cancer Res |
COUNTRY: United States |
ISSNLINKING: 1078-0432 |
NLMUNIQUEID: 9502500 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Meta-Analysis |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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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 |
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KEYWORDS |
|
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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 |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
|
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CHEMICALS |
|
REGISTRYNUMBER |
NAMEOFSUBSTANCE |
0 |
Anticarcinogenic Agents |
0 |
Pyrazoles |
0 |
Sulfonamides |
JCX84Q7J1L |
Celecoxib |
|
OTHER ID's |
|
OTHERID |
SOURCE |
NIHMS588437 |
NLM |
PMC4037290 |
NLM |
|
|