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Melnik et al. J Transl Genet Genom 2022;6:1-45 https://dx.doi.org/10.20517/jtgg.2021.37 Page 23

Pasteurization of milk was introduced as an unproven technology without prior scientific information of its
long-term effects on human health. Pasteurization combined with refrigeration allowed the large-scale
introduction of milk’s epigenetic signaling machinery into the human food chain, recently promoted as a
[628]
nutritional and therapeutic opportunity . In contrast to UHT processing of milk, milk EV-derived miRs
survive pasteurization, as recently confirmed . We are very concerned that food augmentation with
[629]
[450]
oncogenic MEX-derived miRs will further promote milk-related cancers such as PCa and breast cancer .
From the medical point of view, we claim to remove milk’s EVs and MEX from the human food chain to
avoid their oncogenic effects .
[450]
Cow milk consumption in Western societies is a lifelong exposure beginning during fetal life. The fact that
maternal milk consumption promotes fetal growth [580-583] implies early effects on prostate development and
morphogenesis. In contrast to fermented milk (cheese), only maternal milk intake is correlated with
BW [580-583] and increased risk of PCa . It is thus of critical concern that webpages of medical societies such
[10]
as the American College of Obstetricians and Gynecologists and John Hopkins Medicine still promote
[631]
[630]
milk intake during pregnancy and do not differentiate between the biological effects of milk and those of
fermented milk products on fetal development. The next vulnerable window for milk-mediated
disturbances is puberty, the period of final morphogenesis of the prostate. Milk-mediated over-stimulation
of the sebaceous gland (acne vulgaris), skeletal growth (linear overgrowth), and invisible and undetected
changes of the prostatic gland (the potential seeding period of PCa) occur apparently simultaneously during
puberty when young men consume milk, especially when fortified with whey protein concentrates
[632]
combined with androgen abuse to increase muscle mass and physical appearance . In concert with
obstetricians and gynecologists, pediatricians recommend milk intake for children and federal governments
[633]
support school milk consumption . According to Agostoni et al. , a maximum daily intake of 500 mL
[634]
cow milk should be provided to children above the age of 12 months. Although these authors appreciated
milk-induced increases of IGF-1 and linear growth, they neglected associations with noncommunicable
diseases . Puberty with the final differentiation of the prostatic gland appears to be a very vulnerable life
[634]
period for milk’s impact on PCa pathogenesis, a critical issue that is only addressed in two epidemiological
studies [10,168] but no clinical study.

For adult men, further continuous milk consumption is recommended by orthopedics as a valuable source
of calcium for the putative prevention of bone loss [161,635,636] . Thus, important disciplines of Western medicine
promote milk consumption during lifetime with very restricted views to the demands of their own specialty.
There is no epidemiological study that provides data for milk intake over all vulnerable periods of life. There
is no epidemiological study paying attention to the thermal processing of milk, which affects the
bioavailability of milk EVs. Very recent evidence in rodent models demonstrates that bovine milk EVs
promote cancer metastasis . Further studies of the protooncogene MDM4 as a central node of bovine
[637]
MEX interconnectivity may be promising for a deeper understanding of milk’s impact on PCa pathogenesis.
We hope that our review stimulates urologic oncology to address these questions in future research to
prevent epidemic PCa.

DECLARATIONS
Acknowledgments
The authors thank Claus Leitzmann, University of Giessen, Germany and Harald zur Hausen, German
Cancer Reseach Center (DKFZ) for constructive discussions of milk’s impact on human health.

Authors’ contributions
Conception and design: Melnik BC