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Mammary Gland Density Predicts the Cancer Inhibitory Activity of the N-3 to N-6 Ratio of Dietary Fat.
MedLine Citation:
PMID:  21813405     Owner:  NLM     Status:  Publisher    
Background This study investigated the effect of a broad range of dietary ratios of n-3:n-6 fatty acids on mammary gland density (MD) and mammary cancer risk. Methods Cancer was induced in female rats by N-methyl-N-nitrosourea. Purified diet that provided 30% of dietary kcal from fat was formulated to contain ratios of n-3:n-6 fatty acids from 25:1 to 1:25. MD was determined by digital analysis, fatty acids by gas chromatography/flame ionization detection and other plasma analytes via ELISA. Results MD was reduced dose dependently at n-3:n-6 ratios from 1:1 to 25:1 (r=-0.477, P=0.038), with a 20.3% decrease of MD between n-3:n-6 of 1:1 versus 25:1, P<0.001. Mammary carcinogenesis was inhibited in the absence or presence of tamoxifen (1 mg/kg diet) in a manner predicted by MD. Plasma n-3 fatty acid concentrations failed to increase above an n-3:n-6 ratio of 5:1, and changes in specific plasma n-3 or n-6 fatty acids were not predictive of MD or cancer inhibitory activity. A strong reciprocal effect of the n-3:n-6 ratio on plasma leptin (decreased, P=0.005) and adiponectin (increased, P<0.001) was observed indicating adipose tissue function was modulated. However, neither cytokine was predictive of MD. Plasma IGF-1 decreased with increasing dietary n-3:n-6 ratio (P=0.004) and was predictive of the changes in MD (r=0.362, P<0.005).Conclusions These findings indicate that 1) MD predicted the carcinogenic response, 2) the n-3:n-6 ratio exerts effects in the presence or absence of hormonal regulation of carcinogenesis and 3) signaling pathways regulated by IGF-1 are potential targets for further mechanistic investigation.
Zongjian Zhu; Weiqin Jiang; John N McGinley; Bogdan Prokopczyk; John P Richie; Karam El-Bayoumy; Andrea Manni; Henry J Thompson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-2
Journal Detail:
Title:  Cancer prevention research (Philadelphia, Pa.)     Volume:  -     ISSN:  1940-6215     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101479409     Medline TA:  Cancer Prev Res (Phila)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1Cancer Prevention Laboratory, Colorado State University.
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