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

Brock C. Christensen, Karl T. Kelsey, Shichun Zheng, E. Andres Houseman, Carmen J. Marsit, Margaret R. Wrensch, Joseph L. Wiemels, Heather H. Nelson, Margaret R. Karagas, Lawrence H. Kushi, Marilyn L. Kwan, John K. Wiencke

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalPLoS Genetics
Volume6
Issue number7
StatePublished - 2010
Externally publishedYes

Fingerprint

methylation
DNA methylation
DNA Methylation
Folic Acid
folic acid
tumor
breast neoplasms
Methylation
alcohol
cancer
alcohols
Alcohols
Breast Neoplasms
DNA
neoplasms
Neoplasms
loci
gene
Neoplasm Genes
Progesterone Receptors

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Christensen, B. C., Kelsey, K. T., Zheng, S., Houseman, E. A., Marsit, C. J., Wrensch, M. R., ... Wiencke, J. K. (2010). Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake. PLoS Genetics, 6(7).

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

In: PLoS Genetics, Vol. 6, No. 7, 2010.

Research output: Contribution to journalArticle

Christensen, BC, Kelsey, KT, Zheng, S, Houseman, EA, Marsit, CJ, Wrensch, MR, Wiemels, JL, Nelson, HH, Karagas, MR, Kushi, LH, Kwan, ML & Wiencke, JK 2010, 'Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake.', PLoS Genetics, vol. 6, no. 7.
Christensen BC, Kelsey KT, Zheng S, Houseman EA, Marsit CJ, Wrensch MR et al. Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake. PLoS Genetics. 2010;6(7).
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. / Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake. In: PLoS Genetics. 2010 ; Vol. 6, No. 7.
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