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@article{Johansson:2019:10.1371/journal.pmed.1002724,
author = {Johansson, M and Carreras-Torres, R and Scelo, G and Purdue, MP and Mariosa, D and Muller, DC and Timpson, NJ and Haycock, PC and Brown, KM and Wang, Z and Ye, Y and Hofmann, JN and Foll, M and Gaborieau, V and Machiela, MJ and Colli, LM and Li, P and Garnier, J-G and Blanche, H and Boland, A and Burdette, L and Prokhortchouk, E and Skryabin, KG and Yeager, M and Radojevic-Skodric, S and Ognjanovic, S and Foretova, L and Holcatova, I and Janout, V and Mates, D and Mukeriya, A and Rascu, S and Zaridze, D and Bencko, V and Cybulski, C and Fabianova, E and Jinga, V and Lissowska, J and Lubinski, J and Navratilova, M and Rudnai, P and Benhamou, S and Cancel-Tassin, G and Cussenot, O and Weiderpass, E and Ljungberg, B and Tumkur, Sitaram R and Häggström, C and Bruinsma, F and Jordan, SJ and Severi, G and Winship, I and Hveem, K and Vatten, LJ and Fletcher, T and Larsson, SC and Wolk, A and Banks, RE and Selby, PJ and Easton, DF and Andreotti, G and Beane, Freeman LE and Koutros, S and Männi},
doi = {10.1371/journal.pmed.1002724},
journal = {PLoS Medicine},
title = {The influence of obesity-related factors in the etiology of renal cell carcinoma - a mendelian randomization study},
url = {http://dx.doi.org/10.1371/journal.pmed.1002724},
volume = {16},
year = {2019}
}

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TY  - JOUR
AB  - BackgroundSeveral obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findingsGenetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.ConclusionsThis study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
AU  - Johansson,M
AU  - Carreras-Torres,R
AU  - Scelo,G
AU  - Purdue,MP
AU  - Mariosa,D
AU  - Muller,DC
AU  - Timpson,NJ
AU  - Haycock,PC
AU  - Brown,KM
AU  - Wang,Z
AU  - Ye,Y
AU  - Hofmann,JN
AU  - Foll,M
AU  - Gaborieau,V
AU  - Machiela,MJ
AU  - Colli,LM
AU  - Li,P
AU  - Garnier,J-G
AU  - Blanche,H
AU  - Boland,A
AU  - Burdette,L
AU  - Prokhortchouk,E
AU  - Skryabin,KG
AU  - Yeager,M
AU  - Radojevic-Skodric,S
AU  - Ognjanovic,S
AU  - Foretova,L
AU  - Holcatova,I
AU  - Janout,V
AU  - Mates,D
AU  - Mukeriya,A
AU  - Rascu,S
AU  - Zaridze,D
AU  - Bencko,V
AU  - Cybulski,C
AU  - Fabianova,E
AU  - Jinga,V
AU  - Lissowska,J
AU  - Lubinski,J
AU  - Navratilova,M
AU  - Rudnai,P
AU  - Benhamou,S
AU  - Cancel-Tassin,G
AU  - Cussenot,O
AU  - Weiderpass,E
AU  - Ljungberg,B
AU  - Tumkur,Sitaram R
AU  - Häggström,C
AU  - Bruinsma,F
AU  - Jordan,SJ
AU  - Severi,G
AU  - Winship,I
AU  - Hveem,K
AU  - Vatten,LJ
AU  - Fletcher,T
AU  - Larsson,SC
AU  - Wolk,A
AU  - Banks,RE
AU  - Selby,PJ
AU  - Easton,DF
AU  - Andreotti,G
AU  - Beane,Freeman LE
AU  - Koutros,S
AU  - Männistö,S
AU  - Weinstein,S
AU  - Clark,PE
AU  - Edwards,TL
AU  - Lipworth,L
AU  - Gapstur,SM
AU  - Stevens,VL
AU  - Carol,H
AU  - Freedman,ML
AU  - Pomerantz,MM
AU  - Cho,E
AU  - Wilson,KM
AU  - Gaziano,JM
AU  - Sesso,HD
AU  - Freedman,ND
AU  - Parker,AS
AU  - Eckel-Passow,JE
AU  - Huang,W-Y
AU  - Kahnoski,RJ
AU  - Lane,BR
AU  - Noyes,SL
AU  - Petillo,D
AU  - Teh,BT
AU  - Peters,U
AU  - White,E
AU  - Anderson,GL
AU  - Johnson,L
AU  - Luo,J
AU  - Buring,J
AU  - Lee,I-M
AU  - Chow,W-H
AU  - Moore,LE
AU  - Eisen,T
AU  - Henrion,M
AU  - Larkin,J
AU  - Barman,P
AU  - Leibovich,BC
AU  - Choueiri,TK
AU  - Lathrop,GM
AU  - Deleuze,J-F
AU  - Gunter,M
AU  - McKay,JD
AU  - Wu,X
AU  - Houlston,RS
AU  - Chanock,SJ
AU  - Relton,C
AU  - Richards,JB
AU  - Martin,RM
AU  - Davey,Smith G
AU  - Brennan,P
DO  - 10.1371/journal.pmed.1002724
PY  - 2019///
SN  - 1549-1277
TI  - The influence of obesity-related factors in the etiology of renal cell carcinoma - a mendelian randomization study
T2  - PLoS Medicine
UR  - http://dx.doi.org/10.1371/journal.pmed.1002724
UR  - http://hdl.handle.net/10044/1/65537
VL  - 16
ER  -

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