Prostate Cancer Etiology

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The specific factors responsible for the development of prostate cancer are incompletely identified. Research directed at the genetic predisposition towards this disease, as well as its biochemical and environmental correlates demonstrate several new possible pathways toward the development of prostate cancer.

• Signifiant epidemiologic evidence suggests that prostate cancer has both a familial and genetic component.
• Diet. High intake of animal fat is associated with increased prostate cancer risk. Recent epidemiological data suggest that fatty acids may promote or inhibit prostate cancer growth depending on the length of the fatty acid chain. The intake of soy products (isoflavenoids, phytoestrogens, bowman-birk inhibitor) may inhibit the development and progression of prostate cancer.
• Androgens. Endogenous androgens levels are generally higher in African Americans than Caucasians, and may play some role in the development of prostate cancer. On the genetic level, mutations in the androgen receptor [CAG repeats] may affect receptor function.
• Family History. The risk of developing prostate cancer is higher if first and second degree family members are affected.
• It is two-fold higher if one first degree relative is affected and up to eleven-fold if three first degree relatives are affected.
• Familial prostate cancer refers to simple clustering of disease within a family. This may be present in approximately 20% of patients.
• True hereditary prostate cancer is far less common than a familial association and is a subtype of familial prostate cancer with a consistent pattern of inheritance following Mendelian genetics. According to Carter et al, it may be defined as prostate cancer in 3 consecutive generations, a cluster of 3 first-degree relatives, or 2 relatives affected before age 55. It may account for up to 9% of all cancers, but 43% of cancers before the age of 55.
• Odds ratio for patients with one, two, and three affected first degree relatives are 2.2, 4.9, and 10.9, respectively.
• The risk is higher with an affected brother (OR = 3.0) than with an affected father (OR = 2.0). Relative risk for patients with a second-degree affected relative is 1.7, increasing to 8.8 with both first degree and a second-degree affected relatives.
• Prostate cancer risk also increases with a lower age of onset of the proband, being highest when an affected member is younger than 50 years old.
• Several candidate genes are now identified including RNASEL, a latent endoribonuclease that participates in an interferon-inducible RNA decay pathway found on chromosome 1q24-25 and MSR1, the macrophage-scavenger receptor gene located at 8p22. Other genes include PCaP, HCPX, CAPB, HPC2/ELAC, and HPC20.
• To date, only one of six studies have found an association between a positive family history and poor outcome
• Other important genetic alterations with lower penetrance and greater overall impact on prostate cancer development include the promoter methylation, SRD5A2, Cyp17, Cyp 3a4 and the AR gene

References

• Bostwick DG, Burke HB, Djakiew D, et al: Human prostate cancer risk factors. Cancer  2004; 101:2371-2490.
• Carter BS, Bova GS, Beaty TH, Steinberg GD, Childs B, Isaacs WB, Walsh PC. Hereditary prostate cancer: epidemiologic and clinical features. J Urol. 1993 Sep;150(3):797-802.
• Carter BS, Beaty TH, Steinberg GD, Childs B, Walsh PC. Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3367-71.
• Leitzmann MF, Stampfer MJ, Michaud DS, Augustsson K, Colditz GC, Willett WC, Giovannucci EL. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr. 2004 Jul;80(1):204-16.
• Spitz MR, Currier RD, Fueger JJ, Babaian RJ, Newell GR. Familial patterns of prostate cancer: a case-control analysis. J Urol. 1991 Nov;146(5):1305-7.