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.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Christensen BC,Kelsey KT,Zheng S,Houseman EA,Marsit CJ,Wrensch MR,Wiemels JL,Nelson HH,Karagas MR,Kushi LH,Kwan ML,Wiencke JK

doi

10.1371/journal.pgen.1001043

subject

Has Abstract

pub_date

2010-07-29 00:00:00

pages

e1001043

issue

7

eissn

1553-7390

issn

1553-7404

journal_volume

6

pub_type

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