Abstract
Epidemiological studies that have investigated whether dairy (mainly milk) diets are associated with prostate cancer risk have led to controversial conclusions. In addition, no existing study clearly evaluated the effects of dairy/milk diets on prostate tumor progression, which is clinically highly relevant in view of the millions of men presenting with prostate pathologies worldwide, including benign prostate hyperplasia (BPH) or high-grade prostatic intraepithelial neoplasia (HGPIN). We report here a unique interventional animal study to address this issue. We used two mouse models of fully penetrant genetically-induced prostate tumorigenesis that were investigated at the stages of benign hyperplasia (probasin-Prl mice, Pb-Prl) or pre-cancerous PIN lesions (KIMAP mice). Mice were fed high milk diets (skim or whole) for 15 to 27 weeks of time depending on the kinetics of prostate tumor development in each model. Prostate tumor progression was assessed by tissue histopathology examination, epithelial proliferation, stromal inflammation and fibrosis, tumor invasiveness potency and expression of various tumor markers relevant for each model (c-Fes, Gprc6a, activated Stat5 and p63). Our results show that high milk consumption (either skim or whole) did not promote progression of existing prostate tumors when assessed at early stages of tumorigenesis (hyperplasia and neoplasia). For some parameters, and depending on milk type, milk regimen could even exhibit slight protective effects towards prostate tumor progression by decreasing the expression of tumor-related markers like Ki-67 and Gprc6a. In conclusion, our study suggests that regular milk consumption should not be considered detrimental for patients presenting with early-stage prostate tumors.
Highlights
Prostate cancer (Pca) is the second most common cancer in men, with an estimated 900,000 new cases diagnosed worldwide each year [1]
This study was performed to address whether milk consumption may affect prostate tumor progression
The impact of regular milk consumption on the risk of developing a Pca has been addressed in many observational studies, the conclusions are still a matter of intense debate among epidemiologists [5,6]
Summary
Prostate cancer (Pca) is the second most common cancer in men, with an estimated 900,000 new cases diagnosed worldwide each year [1]. Based on the inconsistency of the results (from statistically significant positive association to non-significant inverse association), it was stated that there was limited suggestive evidence that milk and dairy products increased Pca risk [5,6]. These data underline the difficulty to accurately estimate the actual impact of milk consumption on human prostate pathogenesis [7]. No recommendation was provided for dairy intakes since the limited evidence for Pca conflicted with decreased risk of colorectal cancer with high milk intake [5,8]
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