@article{MurphyCarrerasTorresSongetal.2020,
  author    = {Neil Murphy and Robert Carreras-Torres and Mingyang Song and Andrew T. Chan and Richard M. Martin and Nikos Papadimitriou and Niki Dimou and Konstantinos K. Tsilidis and Barbara Banbury and Kathryn E. Bradbury and Jelena Besevic and Sabina Rinaldi and Elio Riboli and Amanda J. Cross and Ruth C. Travis and Claudia Agnoli and Demetrius Albanes and Sonja I. Berndt and St{\´e}phane B{\´e}zieau and D. Timothy Bishop and Hermann Brenner and Daniel D. Buchanan and N. Charlotte Onland-Moret and Andrea Burnett-Hartman and Peter T. Campbell and Graham Casey and Sergi Castellv{\´i}-Bel and Jenny Chang-Claude and Mar{\´i}a-Dolores Chirlaque and Albert de la Chapelle and Dallas English and Jane C. Figueiredo and Steven J. Gallinger and Graham G. Giles and Stephen B. Gruber and Andrea Gsur and Jochen Hampe and Heather Hampel and Tabitha A. Harrison and Michael Hoffmeister and Li Hsu and Wen-Yi Huang and Jeroen R. Huyghe and Mark A. Jenkins and Temitope O. Keku and Tilman K{\"u}hn and Sun-Seog Kweon and Loic Le Marchand and Christopher I. Li and Li Li and Annika Lindblom and Vicente Mart{\´i}n and Roger L. Milne and Victor Moreno and Polly A. Newcomb and Kenneth Offit and Shuji Ogino and Jennifer Ose and Vittorio Perduca and Amanda I. Phipps and Elizabeth A. Platz and John D. Potter and Conghui Qu and Gad Rennert and Lori C. Sakoda and Clemens Schafmayer and Robert E. Schoen and Martha L. Slattery and Catherine M. Tangen and Cornelia M. Ulrich and Fr{\"a}nzel J. B. van Duijnhoven and Bethany Van Guelpen and Kala Visvanathan and Pavel Vodicka and Ludmila Vodickova and Veronika Vymetalkova and Hansong Wang and Emily White and Alicja Wolk and Michael O. Woods and Anna H. Wu and Wei Zheng and Ulrike Peters and Marc J. Gunter},
  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},
  series   = {Gastroenterology},
  volume    = {158},
  number    = {5},
  publisher = {Elsevier},
  issn      = {1528-0012},
  doi       = {10.25968/opus-3166},
  url       = {http://nbn-resolving.de/urn:nbn:de:bsz:960-opus4-31662},
  pages     = {1300 -- 1312},
  year      = {2020},
  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 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.},
  language  = {en}
}