title: Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake.
abstract: Although tumor size and lymph node involvement are the current cornerstones of breast cancer prognosis, they have not been extensively explored in relation to tumor methylation attributes in conjunction with other tumor and patient dietary and hormonal characteristics. Using primary breast tumors from 162 (AJCC stage I-IV) women from the Kaiser Division of Research Pathways Study and the Illumina GoldenGate methylation bead-array platform, we measured 1,413 autosomal CpG loci associated with 773 cancer-related genes and validated select CpG loci with Sequenom EpiTYPER. Tumor grade, size, estrogen and progesterone receptor status, and triple negative status were significantly (Q-values <0.05) associated with altered methylation of 209, 74, 183, 69, and 130 loci, respectively. Unsupervised clustering, using a recursively partitioned mixture model (RPMM), of all autosomal CpG loci revealed eight distinct methylation classes. Methylation class membership was significantly associated with patient race (P<0.02) and tumor size (P<0.001) in univariate tests. Using multinomial logistic regression to adjust for potential confounders, patient age and tumor size, as well as known disease risk factors of alcohol intake and total dietary folate, were all significantly (P<0.0001) associated with methylation class membership. Breast cancer prognostic characteristics and risk-related exposures appear to be associated with gene-specific tumor methylation, as well as overall methylation patterns.
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Brock C
authors.initials: BC
authors.lastname: Christensen
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
authors.forename: Shichun
authors.initials: S
authors.lastname: Zheng
authors.forename: E Andres
authors.initials: EA
authors.lastname: Houseman
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Wiemels
authors.forename: Heather H
authors.initials: HH
authors.lastname: Nelson
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Kushi
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Kwan
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
mesh_terms: D000367:Age Factors; D000428:Alcohol Drinking / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D005492:Folic Acid; D006801:Humans; D044469:Racial Groups; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012307:Risk Factors
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D005492:Folic Acid