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Randomized Controlled Trial
. 2015 Apr;145(4):783-90.
doi: 10.3945/jn.114.202853. Epub 2015 Feb 4.

Dietary modifications, weight loss, and changes in metabolic markers affect global DNA methylation in Hispanic, African American, and Afro-Caribbean breast cancer survivors

Lissette Delgado-Cruzata  1 , Wenfei Zhang  2 , Jasmine A McDonald  3 , Wei Yann Tsai  2 , Cristina Valdovinos  3 , Laura Falci  3 , Qiao Wang  4 , Katherine D Crew  5 , Regina M Santella  6 , Dawn L Hershman  5 , Heather Greenlee  7
Affiliations
Randomized Controlled Trial

Dietary modifications, weight loss, and changes in metabolic markers affect global DNA methylation in Hispanic, African American, and Afro-Caribbean breast cancer survivors

Lissette Delgado-Cruzata et al. J Nutr. 2015 Apr.

Abstract

Background: Lower levels of global DNA methylation in tissue and blood have been associated with increased cancer risk. Conversely, cross-sectional analyses of healthier lifestyle patterns have been associated with higher levels of global DNA methylation.

Objective: In this trial, we explored the associations between changes in lifestyle modifications (diet, weight loss), metabolic markers, and global epigenetic biomarkers in white blood cells.

Methods: Study participants were Hispanic, African American, and Afro-Caribbean overweight and sedentary female breast cancer survivors (n = 24) who participated in a larger randomized, crossover, pilot study of a 6-mo weight loss intervention and who had available blood specimens. Anthropometric measures, a food-frequency questionnaire, and peripheral blood were collected at baseline, 6 mo, and 12 mo. Plasma samples were analyzed for metabolic markers (insulin, glucose). We measured DNA methylation of long interspersed nucleotide element 1 (LINE-1) and satellite 2 by pyrosequencing and MethyLight, respectively, and global DNA methylation by the luminometric methylation assay (LUMA).

Results: DNA methylation of LINE-1 was statistically significantly elevated at 6 mo [75.5% vs. 78.5% (P < 0.0001)] and 12 mo [75.5% vs. 77.7% (P < 0.0001)], compared to baseline. Over a 12-mo period, changes in percentage body fat and plasma glucose concentrations were positively associated with LINE-1 DNA methylation (β = 0.19, P = 0.001) and LUMA DNA methylation levels (β = 0.24, P = 0.02), respectively. Similarly, 12-mo changes in dietary measures such as vegetable (β = 0.009, P = 0.048), protein (β = 0.04, P = 0.001), and total caloric (β = 0.05, P = 0.01) intake were positively associated with changes in LUMA DNA methylation, as was intake of fruit positively associated with changes in LINE-1 DNA methylation (β = 0.004, P = 0.02).

Conclusions: Our hypothesis-generating results suggest that lifestyle modifications may be associated with changes in global DNA methylation detectable at 6 and 12 mo. These biomarkers may be useful intermediate biomarkers to use in future intervention trials. This trial was registered at clinicaltrials.gov as NCT00811824.

Keywords: LINE-1; LUMA; Sat2; epigenetics; weight loss.

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Conflict of interest statement

Author disclosures: L Delgado-Cruzata, W Zhang, JA McDonald, WY Tsai, C Valdovinos, L Falci, Q Wang, KD Crew, RM Santella, DL Hershman, and H Greenlee, no conflicts of interest. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies.

References

    1. Pulte D, Redaniel MT, Brenner H, Jeffreys M. Changes in survival by ethnicity of patients with cancer between 1992–1996 and 2002–2006: is the discrepancy decreasing? Ann Oncol 2012;23:2428–34. - PubMed
    1. Rock CL, Flatt SW, Natarajan L, Thomson CA, Bardwell WA, Newman VA, Hollenbach KA, Jones L, Caan BJ, Pierce JP. Plasma carotenoids and recurrence-free survival in women with a history of breast cancer. J Clin Oncol 2005;23:6631–8. - PubMed
    1. Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA. Physical activity and survival after breast cancer diagnosis. JAMA 2005;293:2479–86. - PubMed
    1. Holmes MD, Stampfer MJ, Colditz GA, Rosner B, Hunter DJ, Willett WC. Dietary factors and the survival of women with breast carcinoma. Cancer 1999;86:826–35. - PubMed
    1. Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld B, Madlensky L, Al-Delaimy WK, Thomson CA, Kealey S, Hajek R, et al. . Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. J Clin Oncol 2007;25:2345–51. - PMC - PubMed

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