Epigenome-wide DNA methylation and risk of breast cancer: a systematic review
Abstract Background DNA 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 f...
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-020-07543-4 |
| _version_ | 1818978402164539392 |
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| author | Kaoutar Ennour-Idrissi Dzevka Dragic Francine Durocher Caroline Diorio |
| author_facet | Kaoutar Ennour-Idrissi Dzevka Dragic Francine Durocher Caroline Diorio |
| author_sort | Kaoutar Ennour-Idrissi |
| collection | DOAJ |
| description | Abstract Background DNA 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. Methods We 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. Results Overall, 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. Conclusions Global 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 number CRD42020147244 |
| first_indexed | 2024-12-20T16:43:04Z |
| format | Article |
| id | doaj.art-c0e1e06975974c20b558075ddbc2b803 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-20T16:43:04Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-c0e1e06975974c20b558075ddbc2b8032022-12-21T19:33:00ZengBMCBMC Cancer1471-24072020-10-0120111010.1186/s12885-020-07543-4Epigenome-wide DNA methylation and risk of breast cancer: a systematic reviewKaoutar Ennour-Idrissi0Dzevka Dragic1Francine Durocher2Caroline Diorio3Department of Social and Preventive Medicine, Faculty of Medicine, Laval UniversityDepartment of Social and Preventive Medicine, Faculty of Medicine, Laval UniversityLaval University Cancer Research CenterDepartment of Social and Preventive Medicine, Faculty of Medicine, Laval UniversityAbstract Background DNA 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. Methods We 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. Results Overall, 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. Conclusions Global 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 number CRD42020147244http://link.springer.com/article/10.1186/s12885-020-07543-4Breast cancer riskDNA methylationEpigenome-wideHM450kSystematic review |
| spellingShingle | Kaoutar Ennour-Idrissi Dzevka Dragic Francine Durocher Caroline Diorio Epigenome-wide DNA methylation and risk of breast cancer: a systematic review BMC Cancer Breast cancer risk DNA methylation Epigenome-wide HM450k Systematic review |
| title | Epigenome-wide DNA methylation and risk of breast cancer: a systematic review |
| title_full | Epigenome-wide DNA methylation and risk of breast cancer: a systematic review |
| title_fullStr | Epigenome-wide DNA methylation and risk of breast cancer: a systematic review |
| title_full_unstemmed | Epigenome-wide DNA methylation and risk of breast cancer: a systematic review |
| title_short | Epigenome-wide DNA methylation and risk of breast cancer: a systematic review |
| title_sort | epigenome wide dna methylation and risk of breast cancer a systematic review |
| topic | Breast cancer risk DNA methylation Epigenome-wide HM450k Systematic review |
| url | http://link.springer.com/article/10.1186/s12885-020-07543-4 |
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