Prostate Cancer - Etiology (part2)
Genetics
Alteration of genes on chromosome 1, 17, and the X chromosome have been found in some patients with a family history of prostate cancer. The hereditary prostate cancer 1 (HPC1) gene and the predisposing for cancer of the prostate (PCAP) gene are on chromosome 1, while the human prostate cancer gene is on the X chromosome. In addition, genetic studies suggest that a strong familial predisposition may be responsible for as many as 5-10% of prostate cancer cases. Recently, several reports have suggested a shared familial risk (inherited or environmental) for prostate and breast cancer. Men with a family history of prostate cancer have a higher risk of developing prostate cancer and are also likely to present 6-7 years earlier.
Race
African American men have a higher prevalence and more aggressive prostate cancer than white men, who, in turn, have a higher prevalence than men of Asian origin. Studies have found that young African American men have testosterone levels 15% higher than young white men. Furthermore, evidence indicates that 5-alpha reductase may be more active in African Americans than in whites, implying that hormonal differences may play a role. The independent contribution of race alone is difficult to qualify when the effects of health care access, income, education, and insurance status are also considered.
Diet
A high-fat diet may lead to increased risks, while a diet rich in soy may be protective. These observations have been proposed as reasons for the low prevalence of this cancer in Asia. Japanese American men have rates of prostate cancer much greater than those of native Japanese men, supporting the association of a high-fat diet with cancer. Cell culture studies have shown that omega-6 fatty acids are positive stimulants of prostate cancer cell growth, while omega-3 fatty acids are negative stimuli. These fats may exert their effects by alterations of sex hormones or growth factors or through effects on 5-alpha reductase.
Soy seems to decrease the growth of prostate cancer cells in mouse models; however, apart from epidemiologic factors, no direct evidence supports a beneficial effect for humans. Vitamin E may have some protective effects because it is an antioxidant. Decreased levels of vitamin A may be a risk factor because this can promote cell differentiation and stimulate the immune system. Vitamin D deficiency was suggested as a risk factor, and studies show an inverse relationship between ultraviolet exposure and mortality rates for prostate cancer. However, a specific correlation between 1,25-dihydroxyvitamin D levels and palpable disease, well-differentiated tumors, or mortality is inconclusive.
Selenium may have a protective effect based on epidemiologic studies, and it is also believed to extend its effect via its antioxidant properties. SELECT, the Selenium and Vitamin E Cancer Prevention Trial, is an ongoing intergroup, phase 3, randomized, controlled trial designed to test the efficacy of selenium and vitamin E alone and in combination in the prevention of prostate cancer.
Hormones
Hormonal causes have also been postulated because androgen ablation causes regression of prostate cancers, and eunuchs do not develop adenocarcinoma of the prostate. Data implicating hormonal causes are indirect evidence, such as that pertaining to eunuchs.
Hsing and Comstock performed a large study comparing patients with prostate cancer with controls and found no difference in testosterone, dihydrotestosterone, prolactin, follicle-stimulating hormone, or estrone.
The Prostate Cancer Prevention Trial studied the prevalence of prostate cancer between a control group and a group given a 5-alpha reductase inhibitor. While the 5-alpha reductase inhibitor appeared to decrease the prevalence of tumors, those that did arise appeared histologically more aggressive. Only long-term follow-up of these patients will determine whether this more aggressive histology accurately reflects the underlying biology of these tumors or whether it is an artifact of the treatment.
Tags: chromosome, Prostate Cancer, sex hormones, testosterone, Vitamin D, Vitamin E