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Genome‐wide association study of peripheral blood DNA methylation and conventional mammographic density measures
Author(s) -
Li Shuai,
Dugué PierreAntoine,
Baglietto Laura,
Severi Gianluca,
Wong Ee Ming,
Nguyen Tuong L.,
Stone Jennifer,
English Dallas R.,
Southey Melissa C.,
Giles Graham G.,
Hopper John L.,
Milne Roger L.
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32171
Subject(s) - dna methylation , mammographic density , breast cancer , methylation , oncology , cohort , medicine , body mass index , biology , genetics , cancer , mammography , dna , gene , gene expression
Age‐ and body mass index (BMI)‐adjusted mammographic density is one of the strongest breast cancer risk factors. DNA methylation is a molecular mechanism that could underlie inter‐individual variation in mammographic density. We aimed to investigate the association between breast cancer risk‐predicting mammographic density measures and blood DNA methylation. For 436 women from the Australian Mammographic Density Twins and Sisters Study and 591 women from the Melbourne Collaborative Cohort Study, mammographic density (dense area, nondense area and percentage dense area) defined by the conventional brightness threshold was measured using the CUMULUS software, and peripheral blood DNA methylation was measured using the HumanMethylation450 (HM450) BeadChip assay. Associations between DNA methylation at >400,000 sites and mammographic density measures adjusted for age and BMI were assessed within each cohort and pooled using fixed‐effect meta‐analysis. Associations with methylation at genetic loci known to be associated with mammographic density were also examined. We found no genome‐wide significant ( p < 10 −7 ) association for any mammographic density measure from the meta‐analysis, or from the cohort‐specific analyses. None of the 299 methylation sites located at genetic loci associated with mammographic density was associated with any mammographic density measure after adjusting for multiple testing (all p > 0.05/299 = 1.7 × 10 −4 ). In summary, our study did not find evidence for associations between blood DNA methylation, as measured by the HM450 assay, and conventional mammographic density measures that predict breast cancer risk.