Abstract
Abstract Available evidence indicates that diets enriched in the ratio of n-3 to n-6 fatty acids have a broad range of health-related benefit; however, the epidemiological and preclinical data for breast cancer risk are mixed. The majority of animal carcinogenesis experiments have been done using diets that were high in the percent of dietary calories provided from fat (40 to 50%) and few studies have investigated the impact of the n-3/n-6 ratio despite the fact that considerable emphasis has been placed on this ratio in hypothesized mechanisms of action. The objective of this investigation was to determine the effect of a wide range of dietary n-3/n-6 ratios on mammary carcinogenesis, on plasma levels of cancer associated growth factors and cytokines and on molecular regulators in mammary carcinomas using a pre-clinical rat model for breast cancer. Female Sprague Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter randomized to groups (n=30/group) in which the n-3/n-6 ratio varied widely and diets were fed in the presence or absence of tamoxifen treatment. Rats were fed a modification of the AIN-93G diet formulation that contained 30% of dietary calories from fat (currently recommended in the US Dietary guidelines). It was observed that mammary cancer incidence, cancer multiplicity and tumor burden were reduced when the dietary ratio of n-3/n-6 was > 5:1. Cancer inhibition was observed in both the presence and absence of tamoxifen. The protective dietary n-3/n-6 ratio was associated with significant reductions in plasma IGF-1, insulin, and leptin and increased adiponectin compared to rats fed the control diet (n-3/n-6=1:1, p<0.05), effects that were not modified by tamoxifen treatment. Carcinomas induced in the protected animals were smaller in mass with altered levels of proteins in the PPAR-NFkB pathway. This work was supported by grant KG081632 from the Susan G. Komen Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3696. doi:10.1158/1538-7445.AM2011-3696
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