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000148846 0247_ $$2doi$$a10.1053/j.gastro.2019.12.020
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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
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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. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.
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000148846 7001_ $$aCarreras-Torres, Robert$$b1
000148846 7001_ $$aSong, Mingyang$$b2
000148846 7001_ $$aChan, Andrew T$$b3
000148846 7001_ $$aMartin, Richard M$$b4
000148846 7001_ $$aPapadimitriou, Nikos$$b5
000148846 7001_ $$aDimou, Niki$$b6
000148846 7001_ $$aTsilidis, Konstantinos K$$b7
000148846 7001_ $$aBanbury, Barbara$$b8
000148846 7001_ $$aBradbury, Kathryn E$$b9
000148846 7001_ $$aBesevic, Jelena$$b10
000148846 7001_ $$aRinaldi, Sabina$$b11
000148846 7001_ $$aRiboli, Elio$$b12
000148846 7001_ $$aCross, Amanda J$$b13
000148846 7001_ $$aTravis, Ruth C$$b14
000148846 7001_ $$aAgnoli, Claudia$$b15
000148846 7001_ $$aAlbanes, Demetrius$$b16
000148846 7001_ $$aBerndt, Sonja I$$b17
000148846 7001_ $$aBézieau, Stéphane$$b18
000148846 7001_ $$aBishop, D Timothy$$b19
000148846 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b20$$udkfz
000148846 7001_ $$aBuchanan, Daniel D$$b21
000148846 7001_ $$aOnland-Moret, N Charlotte$$b22
000148846 7001_ $$aBurnett-Hartman, Andrea$$b23
000148846 7001_ $$aCampbell, Peter T$$b24
000148846 7001_ $$aCasey, Graham$$b25
000148846 7001_ $$aCastellví-Bel, Sergi$$b26
000148846 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b27$$udkfz
000148846 7001_ $$aChirlaque, María-Dolores$$b28
000148846 7001_ $$aChapelle, Albert de la$$b29
000148846 7001_ $$aEnglish, Dallas$$b30
000148846 7001_ $$aFigueiredo, Jane C$$b31
000148846 7001_ $$aGallinger, Steven J$$b32
000148846 7001_ $$aGiles, Graham G$$b33
000148846 7001_ $$aGruber, Stephen B$$b34
000148846 7001_ $$aGsur, Andrea$$b35
000148846 7001_ $$aHampe, Jochen$$b36
000148846 7001_ $$aHampel, Heather$$b37
000148846 7001_ $$aHarrison, Tabitha A$$b38
000148846 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b39$$udkfz
000148846 7001_ $$aHsu, Li$$b40
000148846 7001_ $$aHuang, Wen-Yi$$b41
000148846 7001_ $$aHuyghe, Jeroen R$$b42
000148846 7001_ $$aJenkins, Mark A$$b43
000148846 7001_ $$aKeku, Temitope O$$b44
000148846 7001_ $$0P:(DE-He78)0907a10ba1dc8f53f04907f54f6fdcfe$$aKühn, Tilman$$b45$$udkfz
000148846 7001_ $$aKweon, Sun-Seog$$b46
000148846 7001_ $$aLe Marchand, Loic$$b47
000148846 7001_ $$aLi, Christopher I$$b48
000148846 7001_ $$aLi, Li$$b49
000148846 7001_ $$aLindblom, Annika$$b50
000148846 7001_ $$aMartín, Vicente$$b51
000148846 7001_ $$aMilne, Roger L$$b52
000148846 7001_ $$aMoreno, Victor$$b53
000148846 7001_ $$aNewcomb, Polly A$$b54
000148846 7001_ $$aOffit, Kenneth$$b55
000148846 7001_ $$aOgino, Shuji$$b56
000148846 7001_ $$aOse, Jennifer$$b57
000148846 7001_ $$aPerduca, Vittorio$$b58
000148846 7001_ $$aPhipps, Amanda I$$b59
000148846 7001_ $$aPlatz, Elizabeth A$$b60
000148846 7001_ $$aPotter, John D$$b61
000148846 7001_ $$aQu, Conghui$$b62
000148846 7001_ $$aRennert, Gad$$b63
000148846 7001_ $$aSakoda, Lori C$$b64
000148846 7001_ $$aSchafmayer, Clemens$$b65
000148846 7001_ $$aSchoen, Robert E$$b66
000148846 7001_ $$aSlattery, Martha L$$b67
000148846 7001_ $$aTangen, Catherine M$$b68
000148846 7001_ $$aUlrich, Cornelia M$$b69
000148846 7001_ $$avan Duijnhoven, Franzel Jb$$b70
000148846 7001_ $$aVan Guelpen, Bethany$$b71
000148846 7001_ $$aVisvanathan, Kala$$b72
000148846 7001_ $$aVodicka, Pavel$$b73
000148846 7001_ $$aVodickova, Ludmila$$b74
000148846 7001_ $$aVymetalkova, Veronika$$b75
000148846 7001_ $$aWang, Hansong$$b76
000148846 7001_ $$aWhite, Emily$$b77
000148846 7001_ $$aWolk, Alicja$$b78
000148846 7001_ $$aWoods, Michael O$$b79
000148846 7001_ $$aWu, Anna H$$b80
000148846 7001_ $$aZheng, Wei$$b81
000148846 7001_ $$aPeters, Ulrike$$b82
000148846 7001_ $$aGunter, Marc J$$b83
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