Publikationen

Gastroenterology. 2019 Dec 26. pii: S0016-5085(19)41951-3. doi: 10.1053/j.gastro.2019.12.020

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.

Murphy N¹, Carreras-Torres R², Song M³, Chan AT⁴, Martin RM⁵, Papadimitriou N⁶, Dimou N⁷, Tsilidis KK⁸, Banbury B⁹, Bradbury KE¹⁰, Besevic J¹¹, Rinaldi S¹², Riboli E¹³, Cross AJ¹⁴, Travis RC¹⁵, Agnoli C¹⁶, Albanes D¹⁷, Berndt SI¹⁸, Bézieau S¹⁹, Bishop DT²⁰, Brenner H²¹, Buchanan DD²², Onland-Moret NC²³, Burnett-Hartman A²⁴, Campbell PT²⁵, Casey G²⁶, Castellví-Bel S²⁷, Chang-Claude J²⁸, Chirlaque MD²⁹, Chapelle A³⁰, English D³¹, Figueiredo JC³², Gallinger SJ³³, Giles GG³⁴, Gruber SB³⁵, Gsur A³⁶, Hampe J³⁷, Hampel H³⁸, Harrison TA³⁹, Hoffmeister M⁴⁰, Hsu L⁴¹, Huang WY⁴², Huyghe JR⁴³, Jenkins MA⁴⁴, Keku TO⁴⁵, Kühn T⁴⁶, Kweon SS⁴⁷, Le Marchand L⁴⁸, Li CI⁴⁹, Li L⁵⁰, Lindblom A⁵¹, Martín V⁵², Milne RL⁵³, Moreno V⁵⁴, Newcomb PA⁵⁵, Offit K⁵⁶, Ogino S⁵⁷, Ose J⁵⁸, Perduca V⁵⁹, Phipps AI⁶⁰, Platz EA⁶¹, Potter JD⁶², Qu C⁶³, Rennert G⁶⁴, Sakoda LC⁶⁵, Schafmayer C⁶⁶, Schoen RE⁶⁷, Slattery ML⁶⁸, Tangen CM⁶⁹, Ulrich CM⁷⁰, van Duijnhoven FJ⁷¹, Van Guelpen B⁷², Visvanathan K⁷³, Vodicka P⁷⁴, Vodickova L⁷⁵, Vymetalkova V⁷⁶, Wang H⁷⁷, White E⁷⁸, Wolk A⁷⁹, Woods MO⁸⁰, Wu AH⁸¹, Zheng W⁸², Peters U⁸³, Gunter MJ⁸⁴

Author information

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 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). 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). Colorectal cancer risk was associated with only 1 variant in IGFBP3 (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.

KEYWORDS: CRC, GWAS, risk factors, signal transduction

Publikations ID: 31884074
Quelle: öffnen

Drucken

Schnellinfo

-- Initiative Krebsforschung / Krebsforschungslauf

-- Cancer Care
-- Kliniken und Partner
-- CCC Cancer School
-- Young CCC
-- CCC Tumorboards
-- CCC Forschungscluster
-- CCC Units
-- CCC Platforms
-- SOPs / Leitlinien
-- Kontakt

Zuklappen

Ausklappen

Schnellinfo

Featured