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Title: Mendelian randomization analysis of C-reactive protein on colorectal cancer risk
Author: Wang, Xiaoliang
Dai, James Y.
Albanes, Demetrius
Arndt, Volker
Berndt, Sonja I.
Bézieau, Stéphane
Brenner, Hermann
Buchanan, Daniel D.
Butterbach, Katja
Caan, Bette J.
Casey, Graham
Campbell, Peter T.
Chan, Andrew T.
Chen, Zhengyi
Chang Claude, Jenny
Cotterchio, Michelle
Easton, Douglas F.
Giles, Graham G.
Giovannucci, Edward
Grady, William M.
Hoffmeister, Michael
Hopper, John L.
Hsu, Li
Jenkins, Mark A.
Joshi, Amit D.
Lampe, Johanna W.
Larsson, Susanna C.
Lejbkowicz, Flavio
Li, Li
Lindblom, Annika
Le Marchand, Loic
Martín Sánchez, Vicente
Milne, Roger L.
Moreno Aguado, Víctor
Newcomb, Polly A.
Offit, Kenneth
Ogino, Shuji
Pharoah, Paul D. P.
Pinchev, Mila
Potter, John D.
Rennert, Hedy S.
Rennert, Gad
Saliba, Walid
Schafmayer, Clemens
Schoen, Robert E.
Schrotz King, Petra
Slattery, Martha L.
Song, Mingyang
Stegmaie, Christa
Weinstein, Stephanie J.
Wolk, Alicja
Woods, Michael O.
Wu, Anna H.
Gruber, Stephen B.
Peters, Ulrike
White, Emily
Keywords: Proteïnes
Càncer colorectal
Epidemiologia genètica
Factors de risc en les malalties
Colorectal cancer
Genetic epidemiology
Risk factors in diseases
Issue Date: 1-Jun-2019
Publisher: Oxford University Press
Abstract: Background: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach. Methods: Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk. Results: Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors. Conclusions: In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.
Note: Versió postprint del document publicat a:
It is part of: International Journal of Epidemiology, 2019, vol. 48, num. 3, p. 767-780
Related resource:
ISSN: 0300-5771
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

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