Mendelian randomization analysis of C-reactive protein on colorectal cancer risk

作者：Xiaoliang Wang, James Y. Dai, Demetrius Albanes, Volker Arndt, Sonja I. Berndt, Stéphane Bezieau, Hermann Brenner, Daniel D. Buchanan, Katja Butterbach, Bette J. Caan, Graham Casey, Peter T. Campbell, Andrew T. Chan, Zhengyi Chen, Jenny Chang‐Claude, Michelle Cotterchio, Douglas F. Easton, Graham G. Giles, Edward L. Giovannucci, William M. Grady, Michael Hoffmeister, John L. Hopper, Li Hsu, Mark A. Jenkins, Amit D. Joshi, Johanna W. Lampe, Susanna C. Larsson, Flavio Lejbkowicz, Li Li, Annika Lindblom, Loı̈c Le Marchand, Vicente Martín, Roger L. Milne, Vı́ctor Moreno, Polly A. Newcomb, Kenneth Offitt, Shuji Ogino, Paul D.P. Pharoah, Mila Pinchev, John D. Potter, Hedy S. Rennert, Gad Rennert, Walid Saliba, Clemens Schafmayer, Robert E. Schoen, Petra Schrotz‐King, Martha L. Slattery, Mingyang Song, Christa Stegmaier, Stephanie J. Weinstein, Alicja Wolk, Michael O. Woods, Anna H. Wu, Stephen B. Gruber, Ulrike Peters, Emily White · 发表于：International Journal of Epidemiology · 年份：2018 · DOI：10.1093/ije/dyy244 · 被引用次数：58 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Genetic Associations and Epidemiology、Inflammatory Biomarkers in Disease Prognosis

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 = 0.2...