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

International Journal of Epidemiology
Xiaoliang WangEmily White

Abstract

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. 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. Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, res...Continue Reading

Citations

Jul 9, 1998·Statistical Methods in Medical Research·R Doll
Jan 30, 2002·Clinica Chimica Acta; International Journal of Clinical Chemistry·Sarah de Ferranti, Nader Rifai
Mar 27, 2002·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·A D BlannA D Baildam
Apr 5, 2002·Journal of Vascular Surgery·Edith M Roumen-KlappeHub Wollersheim
Dec 20, 2002·Nature·Lisa M Coussens, Zena Werb
Jun 15, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Steven H Itzkowitz, Xianyang Yio
Jun 24, 2004·Journal of the American Geriatrics Society·Lisa H ColbertTamara B Harris
Oct 19, 2004·Seminars in Cancer Biology·Mary PhilipHans Schreiber
Apr 22, 2005·The New England Journal of Medicine·Göran K Hansson
Jul 29, 2005·The New England Journal of Medicine·Jaime García de Tena
Aug 31, 2006·Cardiovascular Drug Reviews·Kailash Prasad
Nov 23, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Claire SiemesBruno H Ch Stricker
Sep 22, 2007·Statistics in Medicine·Debbie A LawlorGeorge Davey Smith
Nov 6, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Polly A NewcombColon Cancer Family Registry
Jun 6, 2008·International Journal of Cancer. Journal International Du Cancer·Konstantinos K TsilidisElizabeth A Platz
Jul 25, 2008·Nature·Alberto MantovaniFrances Balkwill
Jan 9, 2010·Journal of the National Cancer Institute·Kristine H AllinStig E Bojesen
Aug 24, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Katriina HeikkiläMarkus Perola
Oct 16, 2010·International Journal of Cancer. Journal International Du Cancer·Martha L SlatteryCornelia M Ulrich
Mar 19, 2011·International Journal of Epidemiology·Stephen BurgessCRP CHD Genetics Collaboration
Jul 16, 2011·Human Genetics·Ulrike PetersGraham Casey
Jul 28, 2011·Journal of Digestive Diseases·Xi Tao XuShu Dong Xiao
Dec 26, 2012·Gastroenterology·Ulrike PetersColon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium
Oct 12, 2013·Genetic Epidemiology·Stephen BurgessSimon G Thompson
Apr 1, 2014·Epidemiology·Tyler J VanderWeelePeter Kraft
Jul 22, 2014·International Journal of Cancer. Journal International Du Cancer·Katharina NimptschTobias Pischon
Jul 24, 2014·Cancer Causes & Control : CCC·Bo ZhouYingying Xing
Jun 8, 2015·International Journal of Epidemiology·Jack BowdenStephen Burgess
Oct 14, 2017·Biostatistics·Stijn VansteelandtTorben Martinussen

Related Concepts

Study
Observational Study
C-reactive Protein Measurement
Malignant Tumor of Colon
Chronic Inflammation
Etiology
Colorectal Cancer Pathway
Colorectal Cancer Surveillance Consortium
Observation - Diagnostic Procedure
Logistic Models

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Synapse Loss as Therapeutic Target in MS

As we age, the number of synapses present in the human brain starts to decline, but in neurodegenerative diseases this occurs at an accelerated rate. In MS, it has been shown that there is a reduction in synaptic density, which presents a potential target for treatment. Here is the latest research on synapse loss as a therapeutic target in MS.

Artificial Intelligence in Cardiac Imaging

Artificial intelligence (ai) techniques are increasingly applied to cardiovascular (cv) medicine in cardiac imaging analysis. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

Social Learning

Social learning involves learning new behaviors through observation, imitation and modeling. Follow this feed to stay up to date on the latest research.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Single Cell Chromatin Profiling

Techniques like ATAC-seq and CUT&Tag have the potential to allow single cell profiling of chromatin accessibility, histones, and TFs. This will provide novel insight into cellular heterogeneity and cell states. Discover the latest research on single cell chromatin profiling here.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.