Imperial College London
Alternate

ProfessorElioRiboli

Faculty of Medicine, School of Public Health

Chair in Cancer Epidemiology and Prevention
 
 
 
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Contact

 

e.riboli Website CV

 
 
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Assistant

 

Ms Julieta Dourado +44 (0)20 7594 3426

 
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Location

 

152Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bien:2019:10.1007/s00439-019-01989-8,
author = {Bien, SA and Su, Y-R and Conti, DV and Harrison, TA and Qu, C and Guo, X and Lu, Y and Albanes, D and Auer, PL and Banbury, BL and Berndt, SI and Bézieau, S and Brenner, H and Buchanan, DD and Caan, BJ and Campbell, PT and Carlson, CS and Chan, AT and Chang-Claude, J and Chen, S and Connolly, CM and Easton, DF and Feskens, EJM and Gallinger, S and Giles, GG and Gunter, MJ and Hampe, J and Huyghe, JR and Hoffmeister, M and Hudson, TJ and Jacobs, EJ and Jenkins, MA and Kampman, E and Kang, HM and Kühn, T and Küry, S and Lejbkowicz, F and Le, Marchand L and Milne, RL and Li, L and Li, CI and Lindblom, A and Lindor, NM and Martín, V and McNeil, CE and Melas, M and Moreno, V and Newcomb, PA and Offit, K and Pharaoh, PDP and Potter, JD and Qu, C and Riboli, E and Rennert, G and Sala, N and Schafmayer, C and Scacheri, PC and Schmit, SL and Severi, G and Slattery, ML and Smith, JD and Trichopoulou, A and Tumino, R and Ulrich, CM and van, Duijnhoven FJB and Van, Guelpen B and Weinstein, SJ and },
doi = {10.1007/s00439-019-01989-8},
journal = {Human Genetics},
pages = {307--326},
title = {Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer},
url = {http://dx.doi.org/10.1007/s00439-019-01989-8},
volume = {138},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10- 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10- 4, replication P = 6.7 × 10- 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. Thi
AU  - Bien,SA
AU  - Su,Y-R
AU  - Conti,DV
AU  - Harrison,TA
AU  - Qu,C
AU  - Guo,X
AU  - Lu,Y
AU  - Albanes,D
AU  - Auer,PL
AU  - Banbury,BL
AU  - Berndt,SI
AU  - Bézieau,S
AU  - Brenner,H
AU  - Buchanan,DD
AU  - Caan,BJ
AU  - Campbell,PT
AU  - Carlson,CS
AU  - Chan,AT
AU  - Chang-Claude,J
AU  - Chen,S
AU  - Connolly,CM
AU  - Easton,DF
AU  - Feskens,EJM
AU  - Gallinger,S
AU  - Giles,GG
AU  - Gunter,MJ
AU  - Hampe,J
AU  - Huyghe,JR
AU  - Hoffmeister,M
AU  - Hudson,TJ
AU  - Jacobs,EJ
AU  - Jenkins,MA
AU  - Kampman,E
AU  - Kang,HM
AU  - Kühn,T
AU  - Küry,S
AU  - Lejbkowicz,F
AU  - Le,Marchand L
AU  - Milne,RL
AU  - Li,L
AU  - Li,CI
AU  - Lindblom,A
AU  - Lindor,NM
AU  - Martín,V
AU  - McNeil,CE
AU  - Melas,M
AU  - Moreno,V
AU  - Newcomb,PA
AU  - Offit,K
AU  - Pharaoh,PDP
AU  - Potter,JD
AU  - Qu,C
AU  - Riboli,E
AU  - Rennert,G
AU  - Sala,N
AU  - Schafmayer,C
AU  - Scacheri,PC
AU  - Schmit,SL
AU  - Severi,G
AU  - Slattery,ML
AU  - Smith,JD
AU  - Trichopoulou,A
AU  - Tumino,R
AU  - Ulrich,CM
AU  - van,Duijnhoven FJB
AU  - Van,Guelpen B
AU  - Weinstein,SJ
AU  - White,E
AU  - Wolk,A
AU  - Woods,MO
AU  - Wu,AH
AU  - Abecasis,GR
AU  - Casey,G
AU  - Nickerson,DA
AU  - Gruber,SB
AU  - Hsu,L
AU  - Zheng,W
AU  - Peters,U
DO  - 10.1007/s00439-019-01989-8
EP  - 326
PY  - 2019///
SN  - 0340-6717
SP  - 307
TI  - Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer
T2  - Human Genetics
UR  - http://dx.doi.org/10.1007/s00439-019-01989-8
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30820706
UR  - http://hdl.handle.net/10044/1/69446
VL  - 138
ER  -
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