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Transcriptome profiling of the normal breast of women at either high- or average risk for breast cancer [methyl-capture]

ABSTRACT: Transcriptome profiling of the normal breast of women at either high- or average risk for breast cancer [methyl-capture]

PROVIDER: PRJNA691576 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13420100_1.fastq.gz	Fastqsanger.gz
	SRR13420100_2.fastq.gz	Fastqsanger.gz
	SRR13420200_1.fastq.gz	Fastqsanger.gz
	SRR13420200_2.fastq.gz	Fastqsanger.gz
	SRR13420300_1.fastq.gz	Fastqsanger.gz

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Project description:Lymphocyte and breast tissue samples from overweight woman at increased risk of breast cancer before and after 1 month of intermittant energy restriction Introduction Observational studies indicate that weight loss and energy restriction reduce breast cancer risk. Intermittent energy restriction (IER) reduces weight as well as, or more than continuous energy restriction (CER), but its effect on the breast and systemic metabolism as indicators of breast cancer risk are not known. Methods We assessed the effect of IER ( 2 days of 65% energy restriction) for one menstrual cycle on the breast (breast gene expression and fat cell size) and systemic metabolism (insulin resistance, lipids, serum and urine metabolites) in 23 overweight premenopausal women at high risk of breast cancer. Unsupervised hierarchical analysis selected 100 genes with the highest variance between pre and post IER biopsies in 20 subjects, whilst mass spectrometry was used to assess corresponding changes in serum (LCMS) and urine metabolites (GCMS) in 23 subjects in the restricted and unrestricted days of the IER. Results Women lost on average 4.8% (± 2.0) of body weight and 8.0% (± 5.0) of body fat. Insulin resistance (HOMA) was reduced by 29.8% (±17.8) on the restricted days and by 11%(±34) on the unrestricted days of the IER. Over 250 serum and urine metabolites significantly increased or decreased during the two restricted days and most returned to normal after the subsequent five day period . In the breast tissue, approximately half (In 11) of the subjects displayed down regulation of several metabolic pathways including lipid synthesis, growth factors and hormones, whilst epithelial genes including milk proteins, secretoglobulins and mucins were up-regulated and several metabolic pathways down-regulated including lipid synthesis, growth factors and hormones. In the other nine subjects there was no appreciable effect of IER on the breast. CorrespondingThe gene changes were not seen in peripheral blood lymphocytes, and there was no reduction in breast fat cell size. The two groups defined by change in gene expression or lack of it did not differ in the degree of weight or fat loss, other systemic metabolic markers, or histological assessment of the biopsies. Conclusion We conclude that breasts vary in response to short-term IER, the mechanism of which requires further investigation. Trial registration ISRCTN77916487

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Transcriptome profiling of the normal breast of women at either high- or average risk for breast cancer [methyl-capture]

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