Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake

• Published in: PLoS genetics Vol. 6; no. 7; p. e1001043
• Main Authors: Christensen, Brock C, Kelsey, Karl T, Zheng, Shichun, Houseman, E Andres, Marsit, Carmen J, Wrensch, Margaret R, Wiemels, Joseph L, Nelson, Heather H, Karagas, Margaret R, Kushi, Lawrence H, Kwan, Marilyn L, Wiencke, John K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2010; Public Library of Science (PLoS)
• Subjects: Age Factors; Alcohol Drinking - adverse effects; Biomarkers; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Care and treatment; Continental Population Groups; Deoxyribonucleic acid; Development and progression; Disease; DNA; DNA Methylation; Epigenetics; Female; Folic Acid; Genetic aspects; Genetics and Genomics/Cancer Genetics; Genetics and Genomics/Epigenetics; Health aspects; Humans; Logistics; Medical prognosis; Methylation; Oncology/Breast Cancer; Physiological aspects; Prognosis; Public Health and Epidemiology; Public Health and Epidemiology/Environmental Health; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Risk Factors; Studies; Tumors; Womens health; United States
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1001043

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.