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0 reviewsNo study has systematically compared the suitability of DNA methylation(DNAme) profiles in non-invasive samples for the detection of breast cancer1234567890():,;1234567890():,;(BC). We assess non-tumour DNAme in 1,100 cervical, buccal, and bloodsamples from BC cases and controls and find that cervical samples exhibit thelargest nuber of differentially methylated sites, followed by buccal samples. Nosites were significant in blood after FDR adjustment. Deriving DNAme-basedclassifiers for BC detection in each sample type (WID-buccal-, cervical-, orblood-BC), we achieve validation AUCs of 0.75, 0.66, and 0.51, respectively.Buccal and cervical BC-associated DNAme alterations distinguish between BCcases and controls in both surrogate and breast tissue (AUC > 0.88), yet individual sites and the directionality of methylation changes are not identicalbetween these two sample types, and buccal sample DNAme aligns with breastmethylation changes more closely. Pending additional validation, theseinsights may have the potential to improve non-invasive personalized BCprevention.
