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Prostate Cancer: Etiology

Guidelines and review literature: (EAU Guidelines Prostate Cancer) (S3-Leitlinie Prostatakarzinom) (Walsh-Campbell Urology).

Etiology of Prostate Cancer

Genes are not everything: "Genes load the gun, but lifestyle pulls the trigger", aphorism by Elliott Joslin. Review literature: (DeMarzo et al., 2003).

Genetic Predisposition

Ethnicity:

The different incidences of prostate cancer depending on ethnic background suggest a genetic predisposition to prostate carcinoma. The risk for prostate cancer in the United States are highest for black men, followed by white men and are lowest for asian men. The prostate cancer risk for asian men living in the US amounts to 50–100% of the incidence compared to white men, which is much higher compared to incidence figures from Asia. The responsible environmental factors have not yet been clearly identified, differences in nutrition is probably most crucial.

Familial prostate cancer:

Familial prostate cancer is present, by definition, if either at least three members are affected by prostate cancer (or at least two members under 55 years). Overall the proportion of familial prostate cancer is 9%. In contrast, for men with prostate cancer before the age of 55, 30–40% have familial prostate cancer. Several dominantly inherited genes are thought to be responsible. The risk for prostate cancer is doubled if one first-degree relative is diagnosed with prostate cancer. The risk rises to the 5 to 11-fold, if several first-degree relatives are diagnosed with prostate cancer (Bratt et al., 2002).

Molecular factors

Most prostate cancers are not caused by a few inherited genes with high penetrance. A combination of different genetic polymorphisms lead (together with a risky lifestyle) to prostate cancer. A variety of molecular changes have been described: activation of PI₃/Akt signaling, PTEN/MMAC tumor suppressor gene, epigenetic changes such as DNA methylation, epidermal growth factor receptor (EGFR), telomerase, Glutathione-S-transferase pi, p27 tumor suppressor gene, translocations on chromosome 8q, probably with activation of Myc oncogene, gene deletions on chromosome 8p, p53 tumor suppressor gene, bcl-2, cadherins, IGF-1, changes in the extracellular matrix, increased angiogenesis, MAPK, COX-2, VEGF (vascular endothelial growth factor) and sVCAM-1 (soluble vascular cell adhesion molecule-1).

Chronic inflammation and prostate cancer risk

Chronic prostatitis increases the risk for prostate cancer. This is explained by the chronic release of cell mediators and generation of reactive oxygen species. Chronic inflammation together with certain genetic changes (see above) constitute the first androgen-independent step in the pathogenesis of prostate cancer. The use of acetylsalicylic acid reduces the risk of prostate cancer by 30% (relative risk 0.7), but the data are still scanty .

Testosterone and androgen receptor changes

Prostate cancer does not arise in eunuchs. Castration results in a significant slowing of advanced disease. However, testosterone is not considered to be a carcinogen, but rather act as a promoter in growing tumors. A testosterone concentration in the upper quartile results in a two-fold risk of developing prostate cancer. Several genetic polymorphisms of the androgen receptors increase the risk for prostate cancer.

Environmental factors

The incidence of clinically insignificant prostate cancer is the same all over the world. The increased prostate cancer risk of asian men emigrated to the United States proves the influence of environmental factors as a cause of prostate cancer. The best data is available for diet and prostate cancer risk.

Diet:

Many food components are known to increase or decrease the prostate cancer risk (Masko et al., 2013). However, a special diet to avoid prostate cancer is not possible. General recommendations are helpful such as normalization of body weight, increasing physical activity, healthy diet with a focus on vegetables and reduction of alcohol consumption.

High-fat food:

Food rich of animal fats increase the risk of developing advanced prostate cancer.

Soy-rich diet:

A soy-rich diet is protective against the development of a prostate carcinoma. Responsible isoflavones in soy products are among others genistein, daidzein, and glycetin. Isoflavones are phytoestrogens (Zhang et al., 2016).

Selenium deficiency:

Selenium deficiency is considered a risk factor for prostate cancer. The subsitution of selenium has reduced (in some studies) the risk of a prostate cancer. The protective effect of selenium is explained by different mechanisms: antioxidant activity, improved immune function, inducing apoptosis and reduction of cell proliferation. The SELECT study showed no difference in prevention of prostate cancer.

Diet without sea food:

A diet without sea food can double or triple the risk of prostate cancer.

Beta-carotene deficiency:

Beta-carotene is the precursor of vitamin A. Beta-carotene deficiency increases the risk of prostate cancer (RR 1.3), the substitution with beta-carotene reduced the risk for prostate cancer (RR 0.68).

Vitamin D deficiency:

Vitamin D deficiency may be a risk factor for prostate cancer. The benefits of vitamin D supplemention is controversial.

Tomato products:

A diet rich in tomato products reduces the risk of prostate cancer. Lycopene is an antioxidant in tomato products and responsible for the decreased risk. In addition, lycopene slows the progression of metastatic prostate cancer.

Smoking:

Smoking is a relevant risk factor for prostate cancer (Kenfield et al., 2011):

Smoking at the time of prostate cancer diagnosis increases the risk for advanced prostate cancer
Smoking is a risk factor for a relapse of prostate cancer after primary treatment (38% vs. 26%)
Smoking is a risk factor for death from prostate cancer (15.3/1000 vs. 9.6/1000 person-years)

Cardiovascular risk factors:

The metabolic syndrome increases the prostate cancer risk.

Alcohol

Alcohol does not affect the prostate cancer risk.

Vasectomy:

Conflicting and controversial data. The increased risk after vasectomy found in some studies may be explained by a higher prevalence of screening.

Sexuality:

Although some studies showed that a history of sexually transmitted diseases or early begin of intercourse is a risk factor for prostate cancer (relative risk 2.3), other studies failed to confirm this.

Other environmental factors:

Conflicting and controversial data for pesticides, electromagnetic fields, polychlorinated biphenyls and dust mite allergy.

Prostate cancer epidemiology

Index

Prostate cancer pathology

Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

References

Bratt 2002 BRATT, O.: Hereditary prostate cancer: clinical aspects.
In: J Urol
168 (2002), Nr. 3, S. 906–13 N. Mottet (Chair), J. Bellmunt, E. Briers (Patient Representative), R.C.N. van den Bergh (Guidelines Associate), M. Bolla, N.J. van Casteren (Guidelines Associate), P. Cornford, S. Culine, S. Joniau, T. Lam, M.D. Mason, V. Matveev, H. van der Poel, T.H. van der Kwast, O. Rouvière, T. Wiegel Guidelines on Prostate Cancer of the European Association of Urology (EAU), https://uroweb.org/guideline/prostate-cancer/.

DeMarzo u.a. 2003 DEMARZO, A. M. ; NELSON, W. G. ; ISAACS, W. B. ; EPSTEIN, J. I.: Pathological and molecular aspects of prostate cancer.
In: Lancet
361 (2003), Nr. 9361, S. 955–64

Gronberg 2003 GRONBERG, H.: Prostate cancer epidemiology.
In: Lancet
361 (2003), Nr. 9360, S. 859–64

Kenfield, S. A.; Stampfer, M. J.; Chan, J. M. & Giovannucci, E. Smoking and prostate cancer survival and recurrence.
JAMA, 2011, 305, 2548-2555

Masko, E. M.; Allott, E. H. & Freedland, S. J. The relationship between nutrition and prostate cancer: is more always better?
Eur Urol, 2013, 63, 810-820.

Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, Langversion 3.1, 2014 AWMF Registernummer: 034/022OL, http://www.awmf.org/leitlinien/detail/ll/043-022OL.html (Zugriff am: 07.02.2016)

Wein, A. J.; Kavoussi, L. R.; Partin, A. P. & Peters, C. A. Campbell-Walsh Urology
. Elsevier, 2015. ISBN 978-1455775675.

Zhang, H.-Y.; Cui, J.; Zhang, Y.; Wang, Z.-L.; Chong, T. & Wang, Z.-M. Isoflavones and Prostate Cancer: A Review of Some Critical Issues.
Chin Med J (Engl), 2016, 129, 341-347

Deutsche Version: Prostatakarzinom