000148846 001__ 148846 000148846 005__ 20240229123036.0 000148846 0247_ $$2doi$$a10.1053/j.gastro.2019.12.020 000148846 0247_ $$2pmid$$apmid:31884074 000148846 0247_ $$2ISSN$$a0016-5085 000148846 0247_ $$2ISSN$$a1528-0012 000148846 0247_ $$2altmetric$$aaltmetric:73439236 000148846 037__ $$aDKFZ-2020-00038 000148846 041__ $$aeng 000148846 082__ $$a610 000148846 1001_ $$aMurphy, Neil$$b0 000148846 245__ $$aCirculating 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. 000148846 260__ $$aPhiladelphia, Pa. [u.a.]$$bSaunders$$c2020 000148846 3367_ $$2DRIVER$$aarticle 000148846 3367_ $$2DataCite$$aOutput Types/Journal article 000148846 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1587469035_30799 000148846 3367_ $$2BibTeX$$aARTICLE 000148846 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000148846 3367_ $$00$$2EndNote$$aJournal Article 000148846 500__ $$a2020 Apr;158(5):1300-1312.e20 000148846 520__ $$aHuman 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.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% 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 x 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 x 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.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. 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