Epigenome-wide DNA methylation and risk of breast cancer: a systematic review

BMC Cancer

Dzevka Dragic¹  Kaoutar Ennour-Idrissi²  Caroline Diorio³  Francine Durocher⁴ 

[1] Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Quebec, QC, Canada;Laval University Cancer Research Center, Quebec, QC, Canada;Axe Oncologie, Centre de recherche du CHU de Québec-Université Laval, 1050 chemin Sainte-Foy, G1S 4L8, Quebec City, QC, Canada;Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Quebec, QC, Canada;Laval University Cancer Research Center, Quebec, QC, Canada;Axe Oncologie, Centre de recherche du CHU de Québec-Université Laval, 1050 chemin Sainte-Foy, G1S 4L8, Quebec City, QC, Canada;Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Laval University, Quebec, QC, Canada;Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Quebec, QC, Canada;Laval University Cancer Research Center, Quebec, QC, Canada;Axe Oncologie, Centre de recherche du CHU de Québec-Université Laval, 1050 chemin Sainte-Foy, G1S 4L8, Quebec City, QC, Canada;Deschênes-Fabia Center for Breast Diseases, Saint-Sacrement Hospital, Quebec, QC, Canada;Laval University Cancer Research Center, Quebec, QC, Canada;Department of Molecular Medicine, Faculty of Medicine, Laval University, Quebec, QC, Canada;

关键词: Breast cancer risk;    DNA methylation;    Epigenome-wide;    HM450k;    Systematic review;   

DOI  :  10.1186/s12885-020-07543-4

来源: Springer

【 摘 要 】

BackgroundDNA methylation is a potential biomarker for early detection of breast cancer. However, robust evidence of a prospective relationship between DNA methylation patterns and breast cancer risk is still lacking. The objective of this study is to provide a systematic analysis of the findings of epigenome-wide DNA methylation studies on breast cancer risk, in light of their methodological strengths and weaknesses.MethodsWe searched major databases (MEDLINE, EMBASE, Web of Science, CENTRAL) from inception up to 30th June 2019, for observational or intervention studies investigating the association between epigenome-wide DNA methylation (using the HM450k or EPIC BeadChip), measured in any type of human sample, and breast cancer risk. A pre-established protocol was drawn up following the Cochrane Reviews rigorous methodology. Study selection, data abstraction, and risk of bias assessment were performed by at least two investigators. A qualitative synthesis and systematic comparison of the strengths and weaknesses of studies was performed.ResultsOverall, 20 studies using the HM450k BeadChip were included, 17 of which had measured blood-derived DNA methylation. There was a consistent trend toward an association of global blood-derived DNA hypomethylation and higher epigenetic age with higher risk of breast cancer. The strength of associations was modest for global hypomethylation and relatively weak for most of epigenetic age algorithms. Differences in length of follow-up periods may have influenced the ability to detect associations, as studies reporting follow-up periods shorter than 10 years were more likely to observe an association with global DNA methylation. Probe-wise differential methylation analyses identified between one and 806 differentially methylated CpGs positions in 10 studies. None of the identified differentially methylated sites overlapped between studies. Three studies used breast tissue DNA and suffered major methodological issues that precludes any conclusion. Overall risk of bias was critical mainly because of incomplete control of confounding. Important issues relative to data preprocessing could have limited the consistency of results.ConclusionsGlobal DNA methylation may be a short-term predictor of breast cancer risk. Further studies with rigorous methodology are needed to determine spatial distribution of DNA hypomethylation and identify differentially methylated sites associated with risk of breast cancer.Prospero registration numberCRD42020147244

【 授权许可】

CC BY