Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/173314
Title: Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses
Author: Murphy, Neil
Carreras Torres, Robert
Song, Mingyang
Chan, Andrew T.
Martin, Richard M.
Papadimitriou, Nikos
Dimou, Niki
Tsilidis, Konstantinos K.
Banbury, Barbara L.
Bradbury, Kathryn E.
Besevic, Jelena
Rinaldi, Sabina
Riboli, Elio
Cross, Amanda J.
Travis, Ruth C.
Agnoli, Claudia
Albanes, Demetrius
Berndt, Sonja I.
Bézieau, Stéphane
Bishop, D. Timothy
Brenner, Hermann
Buchanan, Daniel D.
Onland-Moret, N. Charlotte
Burnett-Hartman, Andrea
Campbell, Peter T.
Casey, Graham
Castellví Bel, Sergi
Chang-Claude, Jenny
Chirlaque, María Dolores
Chapelle, Albert de la
English, Dallas
Figueiredo, Jane C.
Gallinger, Steven J.
Giles, Graham G.
Gruber, Stephen B.
Gsur, Andrea
Hampe, Jochen
Hampel, Heather
Harrison, Tabitha A.
Hoffmeister, Michael
Hsu, Li
Huang, Wen-Yi
Huyghe, Jeroen R.
Jenkins, Mark A.
Keku, Temitope O.
Kühn, Tilman
Kweon, Sun-Seog
Marchand, Loic Le
Li, Christopher I.
Li, Li
Lindblom, Annika
Martín, Vicente
Milne, Roger L.
Moreno Aguado, Víctor
Newcomb, Polly A.
Offit, Kenneth
Ogino, Shuji
Ose, Jennifer
Perduca, Vittorio
Phipps, Amanda I.
Platz, Elizabeth A.
Potter, John D.
Qu, Conghui
Rennert, Gad
Sakoda, Lori C.
Schafmayer, Clemens
Schoen, Robert E.
Slattery, Martha L.
Tangen, Catherine M.
Ulrich, Cornelia M.
van Duijnhoven, Franzel J. B.
Van Guelpen, Bethany
Visvanathan, Kala
Vodicka, Pavel
Vodickova, Ludmila
Vymetalkova, Veronika
Wang, Hansong
White, Emily
Wolk, Alicja
Woods, Michael O.
Wu, Anna H.
Zheng, Wei
Peters, Ulrike
Gunter, Marc J.
Keywords: Càncer colorectal
Insulina
Colorectal cancer
Insulin
Issue Date: 2020
Publisher: Elsevier
Abstract: BACKGROUND & AIMS: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. METHODS: Serum levels of IGF1 and other proteins were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) RESULTS: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 level associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05-1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03-1.12; P = 3.3 × 10-4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06-1.18; P = 4.2 × 10-5). Colorectal cancer risk was associated with only 1 variant in IGFBP3 (rs11977526), which also associated with anthropometric traits and circulating level of IGF2. CONCLUSIONS: In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.
Note: Reproducció del document publicat a: https://doi.org/10.1053/j.gastro.2019.12.020
It is part of: Gastroenterology, 2019, vol. S0016-5085, num. 19, p. 41951-41953
URI: http://hdl.handle.net/2445/173314
Related resource: https://doi.org/10.1053/j.gastro.2019.12.020
ISSN: 0016-5085
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

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