PROSTATE CANCER

Prostate cancer: epidemiology and aetiology
Hormonal influence
Growth of prostate cancer (PC), like benign prostatic epithelium, is under the promotional influence of testosterone and its potent metabolite, dihydrotestosterone. Removal of these androgens by castration largely results in programmed cell death (apoptosis) and involution of the prostate. PC is not seen in eunuchs or people with congenital deficiency of 5αreductase, which converts testosterone to dihydrotestosterone.
Oestrogens, including phyto-oestrogens found in foodstuffs used in Asian and Oriental cuisine, have a similar negative growth effect on PC. This helps explain why these races rarely develop the clinical disease (or die) of prostate cancer, as discussed below.
Other dietary inhibitors of PC growth include vitamins E and D, and the antioxidants lycopene (present in tomatoes) and trace element selenium.

Risk factors
Age is an important risk factor for development of histological PC, the disease being rare below 40 years and becoming increasingly common with rising age, according to postmortem studies. Prevalence of PC rises from 29% in the 6th decade to 67% in the 9th decade. This rise is paralleled several years earlier by an identified premalignant lesion prostatic intraepithelial neoplasia (PIN). However, most prostate cancer does not achieve a clinically recognizable and aggressive state. 75% of prostate cancers are diagnosed in men >65 years, though the incidence amongst men aged 50 - 59 has trebled since the 1970s.

Geographic variation: the disease is more common in Western nations, particularly Scandinavian countries and the United States. The disease is rare in Asia and the Far East, but US migrants from Asia and Japan have a 20-fold increased risk. This suggests an environmental aetiology, such as the Western diet, may be important.

Race: Black men are at greater risk than Caucasians; Asians and Oriental races rarely develop prostate cancer unless they migrate to the West. The world's highest incidence is among US and Jamaican Blacks, although there is little data available regarding African and European Blacks. Jamaica has the highest mortality rate in the world.

Family history: 5 - 10% of prostate cancers are believed to be inherited. Hereditary prostate cancer tends to occur in younger (<60 years) men who have a family history; genetic abnormalities on chromosomes 1q, 8p, Xp and mutations of the BRCA2 gene are reported. The risk of a man developing prostate cancer is doubled if there is one affected first-degree relative, and is 4-fold if there are two.
Some controversy surrounds the possible increased risk of developing PC conferred by sexual overactivity, viral infections, and vasectomy. The balance of data and opinion go against these putative risk factors at present. Exposure to cadmium has been suggested to raise the risk of PC, but no new data have been forthcoming since the 1960s.

Prostate cancer: incidence, prevalence, and mortality
Incidence
The diagnosis of prostate cancer is on the increase, probably as a result of increasing use of serum prostatic specific antigen (PSA) testing for both symptomatic and asymptomatic men, and the use of more extensive prostatic biopsy protocols. In 1999, 24,714 men were diagnosed with prostate cancer in the UK, mean age 72 years. This exceeds the number of men diagnosed with lung cancer, placing prostate cancer as the most commonly diagnosed male cancer (excluding skin).

Prevalence
Currently, it is estimated that a man has a 1 in 12 lifetime risk of being diagnosed with prostate cancer as a result of clinical symptoms, signs, or PSA testing. However, the true prevalence of the disease is hinted at by postmortem studies carried out on men who have died of other causes. These have demonstrated histological evidence of prostate cancer in 10% of men in their 3rd decade, 34% in their 5th decade, to 67% in their 9th. This leads to the concept of ‘latent  prostate cancer a biologically non-aggressive and slow-growing form of the disease, which may be unnecessarily detected by PSA screening.

Mortality
It is estimated that 3% of men die of prostate cancer. Mortality increased slowly in the UK and USA during the 1970s and 80s, peaking in 1990 at 3% per yr. However, in 1991, mortality started to decrease in the USA by 2% per yr. In the UK, there are also signs of reduction in mortality, though smaller. In 2001, 9887 deaths were attributed to prostate cancer in the UK, the second most common form of male cancer death (12% of all). This compares with 8524 deaths due to colorectal cancer and 20,384 due to lung cancer. This recent trend toward a reduction in prostate cancer mortality appears to be due to treatment, perhaps early use of hormone therapy for advanced disease, and increased aggressive treatment of localized disease. It is perhaps too early to hail this reduction as a triumph of PSA screening programmes, as some in the USA have suggested.