title: DNA methylation in peripheral blood measured by LUMA is associated with breast cancer in a population-based study.
abstract: Our purpose was to identify epigenetic markers of breast cancer risk, which can be reliably measured in peripheral blood and are amenable for large population screening. We used 2 independent assays, luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) to measure "global methylation content" in peripheral blood DNA from a well-characterized population-based case-control study. We examined associations between methylation levels and breast cancer risk among 1055 cases and 1101 controls and potential influences of 1-carbon metabolism on global methylation. Compared with women in the lowest quintile of LUMA methylation, those in the highest quintile had a 2.41-fold increased risk of breast cancer (95% confidence interval: 1.83-3.16; P, trend<0.0001). The association did not vary by other key tumor characteristics and lifestyle risk factors. Consistent with LUMA findings, genome-wide methylation profiling of a subset of samples revealed greater promoter hypermethylation in breast cancer case participants (P=0.04); higher LUMA was associated with higher promoter methylation in the controls (P=0.05). LUMA levels were also associated with functional sodium nitroprusside in key 1-carbon metabolizing genes, MTHFR C677T (P=0.001) and MTRR A66G (P=0.018). LINE-1 methylation was associated with neither breast cancer risk nor 1-carbon metabolism. Our results show that global promoter hypermethylation measured in peripheral blood was associated with breast cancer risk.
authors.affiliation: Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Xu
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
authors.forename: Hector
authors.initials: H
authors.lastname: Hernandez-Vargas
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
authors.forename: James G
authors.initials: JG
authors.lastname: Wetmur
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Bradshaw
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)