TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Murphy, Neil
A1  - Carreras-Torres, Robert
A1  - Song, Mingyang
A1  - Chan, Andrew T.
A1  - Martin, Richard M.
A1  - Papadimitriou, Nikos
A1  - Dimou, Niki
A1  - Tsilidis, Konstantinos K.
A1  - Banbury, Barbara
A1  - Bradbury, Kathryn E.
A1  - Besevic, Jelena
A1  - Rinaldi, Sabina
A1  - Riboli, Elio
A1  - Cross, Amanda J.
A1  - Travis, Ruth C.
A1  - Agnoli, Claudia
A1  - Albanes, Demetrius
A1  - Berndt, Sonja I.
A1  - Bézieau, Stéphane
A1  - Bishop, D. Timothy
A1  - Brenner, Hermann
A1  - Buchanan, Daniel D.
A1  - Onland-Moret, N. Charlotte
A1  - Burnett-Hartman, Andrea
A1  - Campbell, Peter T.
A1  - Casey, Graham
A1  - Castellví-Bel, Sergi
A1  - Chang-Claude, Jenny
A1  - Chirlaque, María-Dolores
A1  - Chapelle, Albert de la
A1  - English, Dallas
A1  - Figueiredo, Jane C.
A1  - Gallinger, Steven J.
A1  - Giles, Graham G.
A1  - Gruber, Stephen B.
A1  - Gsur, Andrea
A1  - Hampe, Jochen
A1  - Hampel, Heather
A1  - Harrison, Tabitha A.
A1  - Hoffmeister, Michael
A1  - Hsu, Li
A1  - Huang, Wen-Yi
A1  - Huyghe, Jeroen R.
A1  - Jenkins, Mark A.
A1  - Keku, Temitope O.
A1  - Kühn, Tilman
A1  - Kweon, Sun-Seog
A1  - Le Marchand, Loic
A1  - Li, Christopher I.
A1  - Li, Li
A1  - Lindblom, Annika
A1  - Martín, Vicente
A1  - Milne, Roger L.
A1  - Moreno, Victor
A1  - Newcomb, Polly A.
A1  - Offit, Kenneth
A1  - Ogino, Shuji
A1  - Ose, Jennifer
A1  - Perduca, Vittorio
A1  - Phipps, Amanda I.
A1  - Platz, Elizabeth A.
A1  - Potter, John D.
A1  - Qu, Conghui
A1  - Rennert, Gad
A1  - Sakoda, Lori C.
A1  - Schafmayer, Clemens
A1  - Schoen, Robert E.
A1  - Slattery, Martha L.
A1  - Tangen, Catherine M.
A1  - Ulrich, Cornelia M.
A1  - Duijnhoven, Fränzel J. B. van
A1  - Van Guelpen, Bethany
A1  - Visvanathan, Kala
A1  - Vodicka, Pavel
A1  - Vodickova, Ludmila
A1  - Vymetalkova, Veronika
A1  - Wang, Hansong
A1  - White, Emily
A1  - Wolk, Alicja
A1  - Woods, Michael O.
A1  - Wu, Anna H.
A1  - Zheng, Wei
A1  - Peters, Ulrike
A1  - Gunter, Marc J.
T1  - 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
JF  - Gastroenterology
N2  - 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 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 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 the IGFBP3 gene region (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.
KW  - CRC
KW  - Dickdarmkrebs
KW  - Risikofaktor
KW  - Signaltransduktion
KW  - Risk Factors
KW  - Signal Transduction
KW  - GWAS
KW  - Serodiagnostik
Y1  - 2020
UN  - https://nbn-resolving.org/urn:nbn:de:bsz:960-opus4-31662
SN  - 1528-0012
SS  - 1528-0012
U6  - https://doi.org/10.25968/opus-3166
DO  - https://doi.org/10.25968/opus-3166
VL  - 158
IS  - 5
SP  - 1300
EP  - 1312
PB  - Elsevier
ER  -