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

Abstract

Background: The "New Western-style Diet" (NWD) characterized by high in fat and low in fiber, vitamin D, calcium, and methyl donors--are 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 (RXRα). This study was to determine the effect of diet in RXRα knockout mice in developing high-grade prostate intraepithelial neoplasia (mPIN).

Methods: Male mice (n = 54) with or without the RXRα 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 RXRα prostate null mice fed NWD (n = 19), 30.8% RXRα prostate null mice fed AIN-76A (n = 13), 42.9% RXRα wild-type mice fed NWD (n = 14), and 12.5% RXRα wild-type mice fed AIN-76A (n = 8). Unconditional Logistic analysis showed a significant joint effect of NWD and RXRα status in developing mPIN 26.3 (95% CI: 2.5-280), but interaction was not significant owing to the small sample size 1.6 (0.09-27.7, P = 0.7441).

Conclusion: This study provides preliminary data to support a joint RXRα-diet effect in prostate carcinogenesis.