Evidence map›Paper›PMID 36945480›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Identifying metabolic features of colorectal cancer liability using Mendelian randomization.

Caroline J Bull, Emma Hazelwood, Joshua A Bell, Vanessa Y Tan, Andrei-Emil Constantinescu, Maria Carolina Borges, Danny N Legge, Kimberly Burrows, Jeroen R Huyghe, Hermann Brenner and 12 more

Open access · greenFull text readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 12 institutions in 6 countries.

Caroline J BullMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.ORCID 0000-0002-2176-5120
Emma HazelwoodMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.ORCID 0000-0002-4888-6037
Joshua A BellMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.ORCID 0000-0001-6892-8786
Vanessa Y TanMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.ORCID 0000-0001-7938-127X
Andrei-Emil ConstantinescuMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.ORCID 0000-0002-7974-5245
Maria Carolina BorgesMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.ORCID 0000-0001-7785-4547
Danny N LeggeTranslational Health Sciences, Bristol Medical School, University of Bristol, UK.ORCID 0000-0002-3897-5861
Kimberly BurrowsMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.ORCID 0000-0002-3208-0389
Jeroen R HuyghePublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Sergi Castellví-BelGastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
Andrew T ChanDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Sun-Seog KweonDepartment of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea.
Loic Le MarchandUniversity of Hawaii Cancer Center, Honolulu, Hawaii, USA.
Li LiDepartment of Family Medicine, University of Virginia, Charlottesville, Virginia, USA.
Iona ChengDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Rish K PaiDepartment of Pathology and Laboratory Medicine, Mayo Clinic, Arizona, Scottsdale, Arizona, USA.
Jane C FigueiredoDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Neil MurphyNutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.ORCID 0000-0003-3347-8249
Marc J GunterNutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.ORCID 0000-0001-5472-6761
Nicholas J TimpsonMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.ORCID 0000-0002-7141-9189
Emma E VincentMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.ORCID 0000-0002-8917-7384
University of Bristol · GBCentre international de recherche sur le cancer · FRBroad Institute · USCedars-Sinai Medical Center · USCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESChonnam National University Hospital · KRFred Hutch Cancer Center · USGerman Cancer Research Center · DEMayo Clinic in Arizona · USUniversity of California, San Francisco · USUniversity of Hawaiʻi at Mānoa · USUniversity of Virginia · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
SWOG Foreign AccrualsU10CA037429 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BLANKE, CHARLES D., MEYSKENS, FRANK L. · 1985 to 2014
$205.2M
USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5M
Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROSNER, BERNARD A · 2000 to 2019
$77.8M
WOMEN'S HEALTH INITIATIVE - CLINICAL COORDINATING CENTER: TASK AREA B - LONG LIFE STUDY VISIT 2 LIMITED HOME VISIT75N92021D00001 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ANDERSON, GARNET L. · 2021 to 2025
$52.0M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI RIMM, ERIC B · 1991 to 2009
$41.8M
PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Temitope O. Keku · 1985 to 2026
$30.5M
Statistical Methods for Integrative Genomics in CancerP01CA196569 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Paul Marjoram · 2016 to 2026
$25.5M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
Intramural NIH HHS Z01 CP010200Medical Research Council MC_UU_00011/1Medical Research Council MC_UU_00011/4Medical Research Council MC_UU_00011/6Medical Research Council MC_UU_12013/1Medical Research Council MR/M012190/1NCATS NIH HHS KL2 TR000421NCI NIH HHS K05 CA152715NCI NIH HHS K05 CA154337NCI NIH HHS P01 CA033619NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS P01 CA196569NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA014089NCI NIH HHS P30 CA015704NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA042182NCI NIH HHS R01 CA048998NCI NIH HHS R01 CA059045NCI NIH HHS R01 CA060987NCI NIH HHS R01 CA063464NCI NIH HHS R01 CA066635NCI NIH HHS R01 CA067941NCI NIH HHS R01 CA072520NCI NIH HHS R01 CA076366NCI NIH HHS R01 CA081488NCI NIH HHS R01 CA097325NCI NIH HHS R01 CA136726NCI NIH HHS R01 CA137178NCI NIH HHS R01 CA143237NCI NIH HHS R01 CA151993NCI NIH HHS R01 CA189184NCI NIH HHS R01 CA197350NCI NIH HHS R01 CA201407NCI NIH HHS R01 CA207371NCI NIH HHS R01 CA242218NCI NIH HHS R03 CA153323NCI NIH HHS R35 CA197735NCI NIH HHS R37 CA054281NCI NIH HHS U01 CA067941NCI NIH HHS U01 CA074783NCI NIH HHS U01 CA074794NCI NIH HHS U01 CA086308NCI NIH HHS U01 CA122839NCI NIH HHS U01 CA137088NCI NIH HHS U01 CA152753NCI NIH HHS U01 CA167551NCI NIH HHS U01 CA167552NCI NIH HHS U01 CA206110NCI NIH HHS U10 CA037429NCI NIH HHS U19 CA148107NCI NIH HHS U24 CA074794NCI NIH HHS UM1 CA167552NCI NIH HHS UM1 CA182883NCI NIH HHS UM1 CA186107NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01 HG004446NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002NHLBI NIH HHS HHSN268201200008CNHLBI NIH HHS HHSN268201200008INHLBI NIH HHS HHSN268201700006CNIA NIH HHS U01 AG018033NIDDK NIH HHS P30 DK034987NIEHS NIH HHS T32 ES013678NIH HHS S10 OD028685Wellcome TrustWHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005
6 · The paper itself

Abstract

Background: Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival. Methods: To investigate whether changes in circulating metabolites characterise the early stages of colorectal cancer (CRC) development, we examined associations between a genetic risk score (GRS) associated with CRC liability (72 single nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N=6,221). Linear regression models were applied to examine associations between genetic liability to colorectal cancer and circulating metabolites measured in the same individuals at age 8, 16, 18 and 25 years. Results: The GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P<0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N=118,466, median age 58y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk. Conclusions: These analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism, and suggest that fatty acids may play an important role in CRC development. Funding: This work was supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol, the Wellcome Trust, the Medical Research Council, Diabetes UK, the University of Bristol NIHR Biomedical Research Centre, and Cancer Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work used the computational facilities of the Advanced Computing Research Centre, University of Bristol - http://www.bristol.ac.uk/acrc/.

Indexed as

ALSPACCCFRCCTSColorectal cancerEpidemiologyGECCOGeneticsMendelian randomizationMetabolismNMRUK Biobank

Identifiers

PMID36945480
PMCPMC10029059
OpenAlexW4323826829

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.