A complete understanding of the causes of prostate cancer remains elusive. The primary risk factors are obesity, age and family history. Prostate cancer is very uncommon in men younger than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70. However, many men never know they have prostate cancer. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes have found prostate cancer in thirty percent of men in their 50s, and in eighty percent of men in their 70s. Men who have first-degree family members with prostate cancer appear to have double the risk of getting the disease compared to men without prostate cancer in the family. This risk appears to be greater for men with an affected brother than for men with an affected father. In the United States in 2005, there were an estimated 230,000 new cases of prostate cancer and 30,000 deaths due to prostate cancer. Men with high blood pressure are more likely to develop prostate cancer. There is a small increased risk of prostate cancer associated with lack of exercise. A 2010 study found that prostate basal cells were the most common site of origin for prostate cancers.
Genetic
Genetic background may contribute to prostate cancer risk, as suggested by associations with race, family, and specific gene variants. Men who have a first-degree relative (father or brother) with prostate cancer have twice the risk of developing prostate cancer, and those with two first-degree relatives affected have a fivefold greater risk compared with men with no family history. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men. In contrast, the incidence and mortality rates for Hispanic men are one third lower than for non-Hispanic whites. Studies of twins in Scandinavia suggest that forty percent of prostate cancer risk can be explained by inherited factors.
No single gene is responsible for prostate cancer; many different genes have been implicated. Mutations in BRCA1 and BRCA2, important risk factors for ovarian cancer and breast cancer in women, have also been implicated in prostate cancer. Other linked genes include the Hereditary Prostate cancer gene 1 (HPC1), the androgen receptor, and the vitamin D receptor. TMPRSS2-ETS gene family fusion, specifically TMPRSS2-ERG or TMPRSS2-ETV1/4 promotes cancer cell growth.
Loss of cancer suppressor genes, early in the prostatic carcinogenesis, have been localized to chromosomes 8p, 10q, 13q,and 16q. P53 mutations in the primary prostate cancer are relatively low and are more frequently seen in metastatic settings, hence, p53 mutations are late event in pathology of prostate cancer. Other tumor suppressor genes that are thought to play a role in prostate cancer include PTEN (gene) and KAI1. "Up to 70 percent of men with prostate cancer have lost one copy of the PTEN gene at the time of diagnosis" Relative frequency of loss of E-cadherin and CD44 has also been observed.Dietary
While a number of dietary factors have been linked to prostate cancer the evidence is still tentative. Evidence supports little role for dietary fruits and vegetables in prostate cancer occurrence. Red meat and processed meat also appear to have little effect in human studies. Evidence from animals studies however raise concerns. Lower blood levels of vitamin D may increase the risk of developing prostate cancer. This may be linked to lower exposure to ultraviolet (UV) light, since UV light exposure can increase vitamin D in the body.
Green tea may be protective (due to its catechins content), although the most comprehensive clinical study indicates that it has no protective effect. Other holistic methods are also studied.
Taking multivitamins more than seven times a week may increase the risks of contracting the disease. This research was unable to highlight the exact vitamins responsible for this increase (almost double), although they suggest that vitamin A, vitamin E and beta-carotene may lie at its heart. It is advised that those taking multivitamins never exceed the stated daily dose on the label. Higher selenium blood levels have been associated with a lower risk of prostate cancer, a trial of supplementation however did not find benefit.
Folic acid supplements have recently been linked to an increase in risk of developing prostate cancer. A ten-year study led by University of Southern California researchers showed that men who took daily folic acid supplements of 1 mg were three times more likely to be diagnosed with prostate cancer than men who took a placebo.
High alcohol intake may increase the risk of prostate cancer and interfere with folate metabolism. Low folate intake and high alcohol intake may increase the risk of prostate cancer to a greater extent than the sole effect of either one by itself. A case control study consisting of 137 veterans addressed this hypothesis and the results were that high folate intake was related to a 79% lower risk of developing prostate cancer and there was no association between alcohol consumption by itself and prostate cancer risk. Folate's effect however was only significant when coupled with low alcohol intake. There is a significant decrease in risk of prostate cancer with increasing dietary folate intake but this association only remains in individuals with low levels of alcohol consumption. There was no association found in this study between folic acid supplements and risk of prostate cancer.Medication exposure
There are also some links between prostate cancer and medications, medical procedures, and medical conditions. Use of the cholesterol-lowering drugs known as the statins may also decrease prostate cancer risk.
Infection or inflammation of the prostate (prostatitis) may increase the chance for prostate cancer while another study shows infection may help prevent prostate cancer by increasing blood to the area. In particular, infection with the sexually transmitted infections chlamydia, gonorrhea, or syphilis seems to increase risk. Finally, obesity and elevated blood levels of testosterone may increase the risk for prostate cancer. There is an association between vasectomy and prostate cancer however more research is needed to determine if this is a causative relationship.
Research released in May 2007, found that US war veterans who had been exposed to Agent Orange had a 48% increased risk of prostate cancer recurrence following surgery.
In 2006, researchers associated a previously unknown retrovirus, Xenotropic MuLV-related virus or XMRV, with human prostate tumors. Subsequent reports on the virus have been contradictory. A group of US researchers found XMRV protein expression in human prostate tumors, while German scientists failed to find XMRV-specific antibodies or XMRV-specific nucleic acid sequences in prostate cancer samples.
