Evidence map›Paper›PMID 26244061›Full record

ArticleClinical epigenetics2015

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis.

Karin van Veldhoven, Silvia Polidoro, Laura Baglietto, Gianluca Severi, Carlotta Sacerdote, Salvatore Panico, Amalia Mattiello, Domenico Palli, Giovanna Masala, Vittorio Krogh and 16 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 6 pooled it
7.2field-weighted citation impact, top 2% of its field
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

76 citing papers in PubMed, 6 syntheses or guidelines pooled it, 118 citations in OpenAlex.

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  7. Prediagnostic White Blood Cell DNA Methylation and Risk of Breast Cancer in the Prostate Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021
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  14. Synthesis, in-vitro,Toxicology research · 2025
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16 more citing papers are in PubMed but not listed here.

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

26 authors at 9 institutions in 3 countries.

Karin van Veldhoven *MRC-PHE Centre for Environment and Health, Imperial College London, London, W2 1PG UK.
Silvia Polidoro *HuGeF Foundation, 52, Via Nizza, Torino, 10126 Italy.
Laura BagliettoHuGeF Foundation, 52, Via Nizza, Torino, 10126 Italy.
Gianluca SeveriHuGeF Foundation, 52, Via Nizza, Torino, 10126 Italy.
Carlotta SacerdoteHuGeF Foundation, 52, Via Nizza, Torino, 10126 Italy.
Salvatore PanicoDepartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
Amalia MattielloDepartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
Domenico PalliMolecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
Giovanna MasalaMolecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
Vittorio KroghEpidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Claudia AgnoliEpidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Rosario TuminoCancer Registry ASP, Ragusa, Italy.
Graziella FrascaCancer Registry ASP, Ragusa, Italy.
Kirsty FlowerEpigenetics Unit, Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, 4th Floor IRDB, Hammersmith Campus, Du Cane Road, London, W12 0NN UK.
Ed CurryEpigenetics Unit, Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, 4th Floor IRDB, Hammersmith Campus, Du Cane Road, London, W12 0NN UK.
Nicholas OrrDivision of Breast Cancer Research, The Institute of Cancer Research, London, UK.
Katarzyna TomczykDivision of Breast Cancer Research, The Institute of Cancer Research, London, UK.
Michael E JonesDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Alan AshworthBreakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.
Anthony SwerdlowDivision of Breast Cancer Research, The Institute of Cancer Research, London, UK.
Marc Chadeau-HyamMRC-PHE Centre for Environment and Health, Imperial College London, London, W2 1PG UK.
Eiliv LundDepartment of Community Medicine, UiT-the Arctic University of Norway, Tromsø, Norway.
Montserrat Garcia-ClosasBreakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.
Torkjel M SandangerDepartment of Community Medicine, UiT-the Arctic University of Norway, Tromsø, Norway.
James M Flanagan *Epigenetics Unit, Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, 4th Floor IRDB, Hammersmith Campus, Du Cane Road, London, W12 0NN UK.
Paolo Vineis *MRC-PHE Centre for Environment and Health, Imperial College London, London, W2 1PG UK.
Imperial College London · GBItalian institute for Genomic Medicine · ITInstitute of Cancer Research · GBBreast Cancer Now · GBFederico II University Hospital · ITFondazione IRCCS Istituto Nazionale dei Tumori · ITPiedmont Reference Center for Epidemiology and Cancer Prevention · ITUiT The Arctic University of Norway · NOUniversity of Ragusa · IT

Funding

Cancer Research UK 13086
6 · The paper itself

Abstract

backgroundInterest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation.

resultsIn EPIC, we found that high epigenome-wide methylation was associated with lower risk of breast cancer (odds ratio (OR) per 1 SD = 0.61, 95 % confidence interval (CI) 0.47-0.80; -0.2 % average difference in epigenome-wide methylation for cases and controls). Specifically, this was observed in gene bodies (OR = 0.51, 95 % CI 0.38-0.69) but not in gene promoters (OR = 0.92, 95 % CI 0.64-1.32). The association was not replicated in NOWAC (OR = 1.03 95 % CI 0.81-1.30). The reasons for heterogeneity across studies are unclear. However, data from the BGS cohort was consistent with epigenome-wide hypomethylation in breast cancer cases across the overlapping 450k probe sites (difference in average epigenome-wide methylation in case and control DNA pools = -0.2 %).

conclusionsWe conclude that epigenome-wide hypomethylation of DNA from pre-diagnostic blood samples may be predictive of breast cancer risk and may thus be useful as a clinical biomarker.

Indexed as

BiomarkerBreast cancerEWASMethylationPeripheral bloodRisk

Identifiers

PMID26244061
PMCPMC4524428
OpenAlexW1849862482

What OpenQuestion holds

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LicenceCC BY
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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.