Genome-wide association study of peripheral blood DNA methylation and conventional mammographic density measures

Shuai Li, Pierre Antoine Dugué, Laura Baglietto, Gianluca Severi, Ee Ming Wong, Tuong L. Nguyen, Jennifer Stone, Dallas R. English, Melissa C. Southey, Graham G. Giles, John L. Hopper, Roger L. Milne

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Abstract

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.

Original languageEnglish
Number of pages6
JournalInternational Journal of Cancer
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • breast cancer
  • DNA methylation
  • epigenetics
  • mammographic density

Cite this

Li, Shuai ; Dugué, Pierre Antoine ; 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. / Genome-wide association study of peripheral blood DNA methylation and conventional mammographic density measures. In: International Journal of Cancer. 2019.
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abstract = "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.",
keywords = "breast cancer, DNA methylation, epigenetics, mammographic density",
author = "Shuai Li and Dugu{\'e}, {Pierre Antoine} and Laura Baglietto and Gianluca Severi and Wong, {Ee Ming} and Nguyen, {Tuong L.} and Jennifer Stone and English, {Dallas R.} and Southey, {Melissa C.} and Giles, {Graham G.} and Hopper, {John L.} and Milne, {Roger L.}",
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Genome-wide association study of peripheral blood DNA methylation and conventional mammographic density measures. / Li, Shuai; Dugué, Pierre Antoine; 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.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Dugué, Pierre Antoine

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AU - Severi, Gianluca

AU - Wong, Ee Ming

AU - Nguyen, Tuong L.

AU - Stone, Jennifer

AU - English, Dallas R.

AU - Southey, Melissa C.

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AU - Milne, Roger L.

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AB - 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.

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