A joint effect of new western diet and retinoid X receptor alpha prostate-specific knockout with development of high-grade prostatic intraepithelial neoplasia in mice-A preliminary study

BACKGROUND The New Western-style Diet (NWD) characterized by high in fat and low in fiber, vitamin D, calcium, and methyl donorsare considered as a risk factor for prostate cancer. Previous studies have shown that premalignant lesions of human prostate have decreased expression of the Retinoid X Receptor alpha (RXRa). This study was to determine the effect of diet in RXRa knockout mice in developing high-grade prostate intraepithelial neoplasia (mPIN). METHODS Male mice (n?=?54) with or without the RXRa prostate null mutation were fed either NWD or AIN-76A control diet for 10 months; prostates were harvested at 11 months of age and examined for prostate mPIN. RESULTS mPIN was seen in 79% of RXRa prostate null mice fed NWD (n?=?19), 30.8% RXRa prostate null mice fed AIN-76A (n?=?13), 42.9% RXRa wild-type mice fed NWD (n?=?14), and 12.5% RXRa wild-type mice fed AIN-76A (n?=?8). Unconditional Logistic analysis showed a significant joint effect of NWD and RXRa status in developing mPIN 26.3 (95% CI: 2.5280), but interaction was not significant owing to the small sample size 1.6 (0.0927.7, P?=?0.7441). CONCLUSION This study provides preliminary data to support a joint RXRa-diet effect in prostate carcinogenesis. Prostate 72:10521059, 2012. (c) 2012 Wiley Periodicals, Inc.