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Melnik et al. J Transl Genet Genom 2022;6:1-45 Journal of Translational
DOI: 10.20517/jtgg.2021.37
Genetics and Genomics

Review Open Access

The endocrine and epigenetic impact of persistent
cow milk consumption on prostate carcinogenesis

1,2
1
3
Bodo C. Melnik , Swen Malte John , Ralf Weiskirchen , Gerd Schmitz 4
1
Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück D-49076,
Germany.
2
Institute for Interdisciplinary Dermatological Prevention and Rehabilitation (iDerm) at the University of Osnabrück, Lower-
Saxonian Institute of Occupational Dermatology (NIB), Osnabrück D-49076, Germany.
3
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University
Hospital Aachen, Aachen D-52074, Germany.
4
Institute for Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, University of Regensburg,
Regensburg D-93053, Germany.
Correspondence to: Prof. Dr. Bodo C. Melnik, Department of Dermatology, Environmental Medicine and Health Theory,
University of Osnabrück, Am Finkenhügel 7a, Osnabrück D-49076, Germany. E-mail: melnik@t-online.de
How to cite this article: Melnik BC, John SM, Weiskirchen R, Schmitz G. The endocrine and epigenetic impact of persistent cow
milk consumption on prostate carcinogenesis. J Transl Genet Genom 2022;6:1-45. https://dx.doi.org/10.20517/jtgg.2021.37

Received: 31 Jul 2021 First Decision: 13 Sep 2021 Revised: 28 Sep 2021 Accepted: 6 Dec 2021 Published: 7 Jan 2022
Academic Editor: Sanjay Gupta Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

Abstract
This review analyzes the potential impact of milk-induced signal transduction on the pathogenesis of prostate
cancer (PCa). Articles in PubMed until November 2021 reporting on milk intake and PCa were reviewed.
Epidemiological studies identified commercial cow milk consumption as a potential risk factor of PCa. The potential
impact of cow milk consumption on the pathogenesis of PCa may already begin during fetal and pubertal prostate
growth, critical windows with increased vulnerability. Milk is a promotor of growth and anabolism via activating
insulin-like growth factor-1 (IGF-1)/phosphatidylinositol-3 kinase (PI3K)/AKT/mechanistic target of rapamycin
complex 1 (mTORC1) signaling. Estrogens, major steroid hormone components of commercial milk of persistently
pregnant dairy cows, activate IGF-1 and mTORC1. Milk-derived signaling synergizes with common driver mutations
of the PI3K/AKT/mTORC1 signaling pathway that intersect with androgen receptor, MFG-E8, MAPK, RUNX2,
MDM4, TP53, and WNT signaling, respectively. Potential exogenously induced drivers of PCa are milk-induced
elevations of growth hormone, IGF-1, MFG-E8, estrogens, phytanic acid, and aflatoxins, as well as milk exosome-
derived oncogenic microRNAs including miR-148a, miR-21, and miR-29b. Commercial cow milk intake, especially
the consumption of pasteurized milk, which represents the closest replica of native milk, activates PI3K-AKT-
mTORC1 signaling via cow milk’s endocrine and epigenetic modes of action. Vulnerable periods for adverse

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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