Journal
FASEB JOURNAL
Volume 26, Issue 6, Pages 2657-2666Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.11-197251
Keywords
epigenetics; biomarker; 1-carbon metabolism
Categories
Funding
- U.S. National Cancer Institute [R01CA109753, 3R01CA109753-04S1]
- Department of Defense [BC031746, W81XWH-06-1-0298]
- National Cancer Institute
- National Institute of Environmental Health and Sciences [UO1CA/ES66572, UO1CA66572, P30CA013696, P30ES009089, P30ES10126]
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Our purpose was to identify epigenetic markers of breast cancer risk, which can be reliably measured in peripheral blood and are amenable for large population screening. We used 2 independent assays, luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) to measure global methylation content in peripheral blood DNA from a well-characterized population-based case-control study. We examined associations between methylation levels and breast cancer risk among 1055 cases and 1101 controls and potential influences of 1-carbon metabolism on global methylation. Compared with women in the lowest quintile of LUMA methylation, those in the highest quintile had a 2.41-fold increased risk of breast cancer (95% confidence interval: 1.83-3.16; P, trend<0.0001). The association did not vary by other key tumor characteristics and lifestyle risk factors. Consistent with LUMA findings, genome-wide methylation profiling of a subset of samples revealed greater promoter hypermethylation in breast cancer case participants (P=0.04); higher LUMA was associated with higher promoter methylation in the controls (P=0.05). LUMA levels were also associated with functional sodium nitroprusside in key 1-carbon metabolizing genes, MTHFR C677T (P=0.001) and MTRR A66G (P=0.018). LINE-1 methylation was associated with neither breast cancer risk nor 1-carbon metabolism. Our results show that global promoter hypermethylation measured in peripheral blood was associated with breast cancer risk.-Xu, X., Gammon, M. D., Hernandez-Vargas, H., Herceg, Z., Wetmur, J. G., Teitelbaum, S. L., Bradshaw, P. T., Neugut, A. I., Santella, R. M., Chen, J. DNA methylation in peripheral blood measured by LUMA is associated with breast cancer in a population-based study. FASEB J. 26, 2657-2666 (2012). www.fasebj.org
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