title: Global DNA methylation and one-carbon metabolism gene polymorphisms and the risk of breast cancer in the Sister Study.
abstract: Global decrease in DNA methylation is a common feature of cancer and is associated with genomic and chromosomal instability. Retrospective case-control studies have reported that cancer patients have lower global methylation levels in blood DNA than do controls. We used prospectively collected samples and a case-cohort study design to examine global DNA methylation and incident breast cancer in 294 cases and a sample of 646 non-cases in the Sister Study, a study of 50 884 women aged 35-74 years who had not been diagnosed with breast cancer at the time of blood draw. Global methylation in DNA from peripheral blood was assessed by pyrosequencing of the LINE-1 repetitive element. Quartiles of LINE-1 methylation levels were associated with the risk of breast cancer in a dose-dependent fashion (P, trend = 0.002), with an increased risk observed among women in the lowest quartile compared with those in the highest quartile (hazard ratio = 1.75; 95% confidence interval 1.19, 2.59). We also examined 22 polymorphisms in 10 one-carbon metabolism genes in relation to both LINE-1 methylation levels and breast cancer. We found three single-nucleotide polymorphisms in those genes associated with LINE-1 methylation: SLC19A1 (rs1051266); MTRR (rs10380) and MTHFR (rs1537514), one of which was also associated with breast cancer risk: MTHFR (rs1537514). PON1 (rs757158) was associated with breast cancer but not methylation.
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Deroo
authors.forename: Sophia C E
authors.initials: SC
authors.lastname: Bolick
authors.forename: Zongli
authors.initials: Z
authors.lastname: Xu
authors.forename: David M
authors.initials: DM
authors.lastname: Umbach
authors.forename: David
authors.initials: D
authors.lastname: Shore
authors.forename: Clarice R
authors.initials: CR
authors.lastname: Weinberg
authors.forename: Dale P
authors.initials: DP
authors.lastname: Sandler
authors.forename: Jack A
authors.initials: JA
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002244:Carbon / Q000378:metabolism*; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D015894:Genome, Human; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D002244:Carbon