Evidence map›Paper›PMID 39580580›Full record

ArticleBritish journal of cancer2025

Associations of blood lipids and LDL cholesterol lowering drug-targets with colorectal cancer risk: a Mendelian randomisation study.

Wing Ching Chan, Lili Liu, Emmanouil Bouras, Verena Zuber, Wanqing Wen, Jirong Long, Dipender Gill, Neil Murphy, Marc J Gunter, Themistocles L Assimes and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Wing Ching Chan *Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. w.chan21@imperial.ac.uk.ORCID http://orcid.org/0000-0001-7090-6551
Lili Liu *Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Emmanouil BourasDepartment of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.ORCID http://orcid.org/0000-0003-1489-5506
Verena ZuberDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Wanqing WenDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Jirong LongDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Dipender GillDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-7312-7078
Neil MurphyNutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.ORCID http://orcid.org/0000-0003-3347-8249
Marc J GunterDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Themistocles L AssimesVA Palo Alto Health Care System, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0003-2349-0009
Luis BujandaDepartment of Gastroenterology, Biodonostia Health Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain.
Stephen B GruberDepartment of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0001-8656-7822
Sébastien KüryNantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France.ORCID http://orcid.org/0000-0001-5497-0465
Brigid M LynchCancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0001-8060-547X
Conghui QuDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Minta ThomasDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-9337-7015
Emily WhiteDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Michael O WoodsMemorial University of Newfoundland, Discipline of Genetics, St. John's, NL, Canada.
Ulrike PetersDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-5666-9318
Christopher I LiDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Andrew T ChanClinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7284-6767
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Konstantinos K TsilidisDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-8452-8472
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Funding

Data sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8M
Cancer Research UK 29019NCI NIH HHS U01 CA167551World Health Organization 001
6 · The paper itself

Abstract

backgroundWhether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear.

methodsUsing two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls). Our main analysis was a multivariable MR (MVMR) with mutual adjustments for LDL-C, HDL-C, and triglycerides. Secondary analyses, including MVMR additionally-adjusting for BMI or diabetes, were also performed.

resultsGenetically-predicted LDL-C was positively associated with CRC risk in the MVMR adjusted for HDL-C and triglycerides (OR = 1.09; 95%CI 1.02-1.16 per SD increase) and additionally-adjusted for BMI (OR = 1.12; 95%CI 1.05-1.21) or diabetes (OR = 1.09; 95%CI 1.02-1.17). Associations were generally consistent across anatomical subsites. No clear evidence of association was found for other lipids, lipoproteins, or LDL-lowering drug-targets.

conclusionsWe found evidence of a weak positive association between LDL-C and CRC that did not appear to be explained by potential pleiotropic pathways such as via HDL-C, triglycerides, BMI, or diabetes.

Indexed as

Cholesterol, LDLColorectal NeoplasmsLipidsAgedCase-Control StudiesCholesterol, HDLFemaleHumansHydroxymethylglutaryl CoA ReductasesMaleMembrane ProteinsMembrane Transport ProteinsMendelian Randomization AnalysisMiddle AgedPolymorphism, Single NucleotideProprotein Convertase 9Cholesterol, HDLCholesterol, LDLHMGCR protein, humanHydroxymethylglutaryl CoA ReductasesLipidsMembrane ProteinsMembrane Transport ProteinsNPC1L1 protein, humanPCSK9 protein, humanProprotein Convertase 9Triglycerides

Identifiers

PMID39580580
PMCPMC11723917

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Registered trials

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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.