National Cancer Institute - Risk Factors

  • Age - Prostate cancer incidence increases dramatically with increasing age. While a very unusual disease in men younger than 50 years, rates increase exponentially thereafter. The registration rate by age cohort in England and Wales increased from 8 per thousand population in men aged 50 to 56 years to 68 per thousand in men aged 60 to 64 years, 260 per thousand in men aged 70 to 74 years, and peaked at 406 per thousand in men aged 75 to 79 years.[1] The death rate per thousand in 1992 in the 50 to 54 years, 60 to 64 years, and 70 to 74 years cohorts in this same population was 4, 37, and 166, respectively.[1] At all ages, incidence of blacks exceeds those of whites. [2]

  • Family History  - Approximately 15% of men with a diagnosis of prostate cancer will be found to have a first-degree male relative (e.g., brother, father) with prostate cancer, compared with approximately 8% of the U.S. population.[3] Approximately 9% of all prostate cancers may result from heritable susceptibility genes.[4] Several authors have completed segregation analyses, and though a single, rare autosomal gene has been suggested to cause cancer in some of these families, the burden of evidence suggests that the inheritance is considerably more complex.[5-7]

  • Hormones  - The development of the prostate is dependent upon the secretion of dihydrotestosterone (DHT) by the fetal testis. Testosterone causes normal virilization of the Wolffian duct structures and internal genitalia and is acted upon by the enzyme 5 alpha-reductase (5AR) to form DHT. DHT has a 4-fold to 50-fold greater affinity for the androgen receptor than testosterone, and it is DHT that leads to normal prostatic development. Children born with abnormal 5AR (due to a change in a single base pair in exon 5 of the normal type II 5AR gene), are born with ambiguous genitalia (variously described as hypospadias with a blind-ending vagina to a small phallus) but masculinize at puberty because of the surge of testosterone production at that time. Clinical, imaging, and histologic studies of kindreds born with 5AR deficiency have demonstrated a small, pancake-appearing prostate with an undetectable prostate-specific antigen (PSA) and no evidence of prostatic epithelium.[8] Long-term follow-up demonstrates that neither benign prostatic hyperplasia (BPH) nor prostate cancer develop.  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: 

    Neither BPH nor prostate cancer have been reported in men castrated prior to puberty.[9]  Androgen levels generally parallel prostate cancer risk in various populations of men. Although data are conflicting, a number of studies have demonstrated that levels of testosterone, and especially DHT, are highest in black males, of intermediate levels in white males, and lowest in native Japanese males.[10-12] The risks of prostate cancer in these ethnic groups directly parallel these androgen levels.  Androgen deprivation in almost all forms leads to involution of the prostate, a fall in PSA levels, apoptosis of prostate cancer and epithelial cells, as well as a clinical response in prostate cancer patients.[13,14]
  • Race  - The risk of prostate cancer is dramatically higher among blacks, is of intermediate levels among whites, and is lowest among native Japanese. Survival is also related to ethnicity with 5-year survival with localized/regional, or metastatic prostate cancer being 100%, and 32.6%, respectively, for whites, compared with rates of 100%, and 30.3%, respectively, for blacks.[15,16] Conflicting data have been published regarding the etiology of these outcomes, but some evidence is available that access to care may play a role in disease outcomes.[17]

  • 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.[18] 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.[19,20] 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.[21,22] Animal models of explanted human prostate cancer have demonstrated decreased tumor growth rates in animals who are fed a low-fat diet.[23,24] Evidence from many case-control studies has generally found an association between dietary fat and prostate cancer risk,[25-27] though studies have not uniformly reached this conclusion.[28-30] 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.[31] Among case-control studies, again, 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 3 studies reported of a significant negative association between prostate cancer and fat intake. In general, fat of animal origin seems to be associated with the highest risk.[17,32] 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.[33] 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 over the same time period.[34,35]

    The explanation for this possible association between prostate cancer and dietary fat is unknown. Several hypotheses have been advanced including:  Dietary fat may increase serum androgen levels, thereby increasing prostate cancer risk. This hypothesis is supported by observations from South Africa and the United States that changes in dietary fat intake change urinary and serum levels of androgens.[36,37]  Certain types of fatty acids or their metabolites may initiate or promote prostate carcinoma development. The evidence for this hypothesis is conflicting, but one study suggests that linoleic acid (omega-6 polyunsaturated fatty acid) may stimulate prostate cancer cells, while omega-3 fatty acids inhibit cell growth.[38]  An observation made in an animal model is that male offspring of pregnant rats who are fed a high-fat diet will develop prostate cancer at a higher rate than animals who are fed a low-fat diet.[39] This observation may explain some of the variations in prostate cancer incidence and mortality among ethnic groups; an observation has been made that first trimester androgen levels in pregnant blacks are higher than those in whites.[40]
  • Dairy and Calcium Intake  -  In a meta-analysis of 10 cohort studies (8 from the U.S. and 2 from Europe), it was concluded that men with the highest intake of dairy products (relative risk [RR] = 1.11; 95% CI, 1.00–1.22; P = .04) and calcium (RR = 1.39; 95% CI, 1.09–1.77; P = .18) were more likely to develop prostate cancer than men with the lowest intake. The pooled RRs of advanced prostate cancer were 1.33 (95% CI, 1.00–1.78; P = .055) for the highest versus lowest intake categories of dairy products and 1.46 (95% CI, 0.65–3.25; P >.2) for the highest versus lowest intake categories of calcium. High intake of dairy products and calcium may be associated with an increased risk of prostate cancer although the increase may be small.[41]

  • Cadmium Exposure  -  Cadmium exposure is occupationally associated with nickel-cadmium batteries and cadmium recovery plant smelters, and is associated with cigarette smoke.[42] The earliest studies of this agent documented an apparent association, but better-designed studies have failed to note an association.[43,44]

  • Dioxin Exposure  -  Dioxin (TCDD or 2,3,7,8 tetrachlorodibenzo-p-dioxin) is a contaminant of an herbicide used in Vietnam. This agent is similar to many components of herbicides used in farming. A review of the linkage between dioxin and prostate cancer risk by the National Academy of Sciences Institute of Medicine Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides, found only 2 articles on prostate cancer with sufficient numbers of cases and follow-up to allow analysis.[45,46] The analysis of all available data suggests that the association between dioxin exposure and prostate cancer is not conclusive.[47]

Screening Info - 2009

  • Majority of men should be offered baseline PSA test in lieu of annual screening, group says.

    The AP (4/27, Marchione) reports, "An influential doctors' group is backing off its call for annual tests after age 50 to screen for prostate cancer," stating that while the majority of "'men do not need yearly screening,'...each man's risk should be individually assessed." Now, the "new stance brings the" American Urological Association "more in line with advice from other experts, who say annual screening is leading to unnecessary biopsies and treatment, with little proof that it saves lives." In fact, AUA's "new advice says men should be offered a baseline PSA test at age 40, and follow-ups at intervals based on each man's situation." But, while some experts laud the move, "others disagreed. There is no proof that a baseline test will save lives, said Dr. Barnett Kramer, a National Institutes of Health scientist." Nonetheless, "many doctors believe the [PSA] test may still have value -- if researchers can figure out better ways to use it." And, "new studies at the urology meeting suggest ways." For instance, "one found that a man's PSA at age 60 can strongly predict whether he ultimately will die of the disease."

Prostate Cancer - Overdiagnosis and Overtreatment - 2009

Changing your genes in 3 steps - Dr. Oz