The Diet as a Cause of Human Prostate Cancer

  • William G. Nelson
  • Angelo M. DeMarzo
  • Srinivasan Yegnasubramanian
Conference paper
Part of the Cancer Treatment and Research book series (CTAR, volume 159)

Abstract

Asymptomatic prostate inflammation and prostate cancer have reached epidemic proportions among men in the developed world. Animal model studies implicate dietary carcinogens, such as the heterocyclic amines from over-cooked meats and sex steroid hormones, particularly estrogens, as candidate etiologies for prostate cancer. Each acts by causing epithelial cell damage, triggering an inflammatory response that can evolve into a chronic or recurrent condition. This milieu appears to spawn proliferative inflammatory atrophy (PIA) lesions, a type of focal atrophy that represents the earliest of prostate cancer precursor lesions. Rare PIA lesions contain cells which exhibit high c-Myc expression, shortened telomere segments, and epigenetic silencing of genes such as GSTP1, encoding the π-class glutathione S-transferase, all characteristic of prostatic intraepithelial neoplasia (PIN) and prostate cancer. Subsequent genetic changes, such as the gene translocations/deletions that generate fusion transcripts between androgen-regulated genes (such as TMPRSS2) and genes encoding ETS family transcription factors (such as ERG1), arise in PIN lesions and may promote invasiveness characteristic of prostatic adenocarcinoma cells. Lethal prostate cancers contain markedly corrupted genomes and epigenomes. Epigenetic silencing, which seems to arise in response to the inflamed microenvironment generated by dietary carcinogens and/or estrogens as part of an epigenetic “catastrophe” affecting hundreds of genes, persists to drive clonal evolution through metastatic dissemination. The cause of the initial epigenetic “catastrophe” has not been determined but likely involves defective chromatin structure maintenance by over-exuberant DNA methylation or histone modification. With dietary carcinogens and estrogens driving pro-carcinogenic inflammation in the developed world, it is tempting to speculate that dietary components associated with decreased prostate cancer risk, such as intake of fruits and vegetables, especially tomatoes and crucifers, might act to attenuate the ravages of the chronic or recurrent inflammatory processes. Specifically, nutritional agents might prevent PIA lesions or reduce the propensity of PIA lesions to suffer “catastrophic” epigenome corruption.

Keywords

Prostate Proliferative inflammatory atrophy Heterocyclic amines Epigenetics DNA methylation 

Abbreviations

PSA

Prostate-specific antigen

BPH

Benign prostatic hyperplasia

PIA

Proliferative inflammatory atrophy

PIN

Prostatic intraepithelial neoplasia

PhIP

Phenylimidazopyridine

GST

Glutathione S-transferase

TLRs

Toll-like receptors

COX

Cyclooxygenase

NSAIDs

Non-steroidal anti-inflammatory drugs

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • William G. Nelson
    • 1
  • Angelo M. DeMarzo
    • 1
  • Srinivasan Yegnasubramanian
    • 1
  1. 1.Departments of Oncology, Pathology, and Urology, Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreUSA

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