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    Prostate Cancer Prevention (PDQ®): Prevention - Health Professional Information [NCI] - Risk Factors for Prostate Cancer Development

    continued...

    Other evidence suggesting that the degree of cumulative exposure of the prostate to androgens is related to an increased risk of prostate cancer includes the following:

    1. Neither BPH nor prostate cancer have been reported in men castrated prior to puberty.[9]
    2. Androgen deprivation in almost all forms leads to involution of the prostate, a fall in PSA levels, apoptosis of prostate cancer and epithelial cells, and a clinical response in prostate cancer patients.[10,11]
    3. The results of two large-scale chemoprevention trials using 5AR inhibitors (finasteride and dutasteride) demonstrate that intraprostatic androgens modulate prostate cancer risk. In both studies, reductions in overall prostate cancer risk were identified although with increased risk of high-grade disease.[12,13]

    Ecological studies have found a correlation between serum levels of testosterone, especially DHT, and overall risk of prostate cancer among African American, white, and Japanese males.[14,15,16] However, evidence from prospective studies of the association between serum concentrations of sex hormones, including androgens and estrogens, does not support a direct link.[17] A collaborative analysis of 18 prospective studies, pooling prediagnostic measures on 3,886 men with incident prostate cancer and 6,438 control subjects, found no association between the risk of prostate cancer and serum concentrations of testosterone, calculated-free testosterone, dihydrotestosterone sulfate, androstenedione, androstanediol glucuronide, estradiol, or calculated-free estradiol.[17] A caution for interpreting the data is the unknown degree of correlation between serum levels and prostate tissue level. Androstanediol glucuronide may most closely reflect intraprostatic androgen activity, and this measure was not associated with the risk of prostate cancer. This lack of association affirms that risk stratification cannot be made on serum hormone concentrations.

    Race

    The risk of developing and dying from prostate cancer is dramatically higher among blacks, is of intermediate levels among whites, and is lowest among native Japanese.[18,19] Conflicting data have been published regarding the etiology of these outcomes, but some evidence is available that access to health care may play a role in disease outcomes.[20]

    Dietary Fat

    An interesting observation is that although the incidence of latent (occult, histologically evident) prostate cancer is similar throughout the world, clinical prostate cancer varies from country to country by as much as 20-fold.[21] Previous ecologic studies have demonstrated a direct relationship between a country's prostate cancer-specific mortality rate and average total calories from fat consumed by the country's population.[22,23] Studies of immigrants from Japan have demonstrated that native Japanese have the lowest risk of clinical prostate cancer, first generation Japanese-Americans have an intermediate risk, and subsequent generations have a risk comparable to the U.S. population.[24,25] Animal models of explanted human prostate cancer have demonstrated decreased tumor growth rates in animals who are fed a low-fat diet.[26,27] Evidence from many case-control studies has found an association between dietary fat and prostate cancer risk,[28,29,30] though studies have not uniformly reached this conclusion.[31,32,33] In a review of published studies of the relationship between dietary fat and prostate cancer risk, among descriptive studies, approximately half found an increased risk with increased dietary fat and half found no association.[34] Among case-control studies, about half of the studies found an increased risk with increasing dietary fat, animal fat, and saturated and monounsaturated fat intake while approximately half found no association. Only in studies of polyunsaturated fat intake were three studies reported of a significant negative association between prostate cancer and fat intake. Fat of animal origin seems to be associated with the highest risk.[20,35] In a series of 384 patients with prostate cancer, the risk of cancer progression to an advanced stage was greater in men with a high fat intake.[36] The announcement in 1996 that cancer mortality rates had fallen in the United States prompted the suggestion that this may be caused by decreases in dietary fat intake during the same time period.[37,38]

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