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