From: Epigenome-wide DNA methylation and risk of breast cancer: a systematic review
Design | Study design  Case-cohort or cohort studies, n = 2  Nested case-control studies, n = 9  Unspecified case-control studies, n = 3  Cross-sectional study, n = 1  Multiple designs, n = 2 Sample size  Total participants, 90 to 228,951  Breast cancer patients, 48 to 122,977 | Population source  Europe, n = 8  Australia, n = 3  USA, n = 2  Europe and/or Australia and/or USA, n = 4 Follow-up  Duration, 2 weeks to > 20 years  Not reported in 9 studies |
Breast cancer patients | Mean age, 48 to 64 years old Postmenopausal, 31 to 100%, NR in 10 studies | Invasive cancers, 88 to 100%, NR in 10 studies ER-positive cancers, 0 to 83%, NR in 9 studies |
DNA methylation measurement | Timing  Before diagnosis, n = 13  After diagnosis, before treatment, n = 2  After diagnosis, unspecified, n = 1  Not reported, n = 1 Cell-type proportions  Estimated (Houseman algorithm), n = 10  Estimated, other method, n = 2  Estimated, method NR, n = 2  Not considered, n = 3 Probe design bias correction method  Functional normalizationa, n = 7  SWANa, n = 7  BMIQ, n = 2  Quantile normalization, n = 2  RCP, n = 1  Not reported, n = 4 | Cross-hybridizing probes  Excluded, n = 5  Not reported, n = 12 Probes with SNP  Excluded, n = 5  Not excluded, n = 1  Not reported, n = 11 X chromosomes  Excluded, n = 5  Included, n = 4  Not reported, n = 8 |
Outcomes | Breast cancer incidence, n = 16 Breast mammographic density, n = 1 | |
Statistical modeling | Global methylation, n = 9 Type of global methylation analysis  Average across all included probesc, n = 6  Average across pre-defined set of probesc, n = 5 Type of methylation value  Beta-values, n = 8  Not reported, n = 1 Statistical model  Logistic regression, n = 5  Cox proportional hazard model, n = 1  Non-parametric test, n = 2  Not reported, n = 1 Adjustment  Appropriate, n = 3  Incomplete, n = 4  None, n = 2 | Probe-wise differential methylation, n = 16 Type of methylation value  Beta-values, n = 10  M-values, n = 4  Not reported, n = 2 Statistical model  Logistic regressionb, n = 6  Cox proportional hazard modelsb, n = 2  Beta-regression, n = 2  Linear mixed effect model, n = 2  MetaXcan method, n = 1  Linear regression with empirical Bayes methods, n = 1  Non-parametric tests, n = 1  Not reported, n = 2 Adjustment  Appropriate, n = 3  Incomplete, n = 12  None, n = 1 Multiple comparison correction  Bonferroni’s correction, n = 6  FDR, n = 3  None, n = 7 |