Table 1 Summary characteristics of blood-derived methylation studies and breast cancer risk (n = 17)
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 |