Zinc is high in the healthy prostate. And a low levels of AZGP1 in the prostate at time of surgery predicts increased risk of developing metastatic cancer.
Yet high dietary zinc intake, a recent study has found, raises the risk of prostate cancer about one and a half times. In fact, according to this study, high intake of dietary zinc doubles the risk of advanced and aggressive prostate cancer--with a high Gleason-- or indeed pushes the risk to a factor of 3.59. The study authors conclude:
In this large study we found a direct association between high zinc intake and prostate cancer risk, particularly for advanced cancers. Our findings allowed us to exclude a favourable effect of zinc on prostate carcinogenesis. Dietary Zinc and Prostate Cancer Risk: A Case-Control Study from Italy. Eur Urol. 2007 Feb 5
If the above sounds confusing, it is. Studies of the effects of dietary zinc on prostate cancer "have been conflicting and confusing," according to Professor Leslie Costello, who has studied the topic for several years. But Costello is pro-zinc.
In a recent study he writes:
The most consistent and persistent biochemical characteristic of prostate cancer (PCa) is the marked decrease in zinc and citrate levels in the malignant cells. This relationship provides compelling evidence that the lost ability of the malignant cells to accumulate zinc is an important factor in the development and progression of prostate malignancy. In addition, this relationship provides a rational basis for the concept that restoration of high zinc levels in malignant cells could be efficacious in the treatment and prevention of PCa. Role of zinc in the pathogenesis and treatment of prostate cancer: critical issues to resolve (2004)
Costello says his team hopes to bring "more attention to the medical and research community of the critical need for concerted clinical and basic research regarding zinc and PCa, for the development of appropriate human prostate models to investigate these relationships, for further appropriately designed epidemiologic studies, and for future well-controlled clinical trials."
Pacific Islands men have one of the highest rates of prostate cancer in the world. One study looked for links between prostate cancer exposure to zinc (Zn) and two other trace minerals -- cadmium (Cd) and selenium (Se). Out of a larger community prostate study group of 1405 men they tested blood samples of 176 men for these minerals and for elevated Prostate Specific Antigen (PSA), a marker of prostate cancer. The researchers looked for possible effect of ethnic differences also:
Maori and Pacific Islands men were found likely to have higher Cd exposure than New Zealand Europeans through diet, occupation and smoking. However, there was no significant difference between ethnic groups in mean blood Cd levels.
Pacific Islands men had significantly higher levels of blood Se than both New Zealand European men and Maori men.
Maori men had significantly higher levels of blood Zn than both New Zealand European men and Pacific Islands men.
A positive association was found between blood Cd and total serum PSA.
Se and Zn levels were not associated with elevated PSA.
Maori and Pacific Islands men have higher prostate cancer mortality rates than New Zealand European men. Ethnic differences in mortality could be contributed to by differences in rates of disease progression, influenced by exposure and/or deficiency to trace elements. However, results did not reflect a consistent ethnic trend and highlight the complexity of the risk/protective mechanisms conferred by exposure factors. Further research is needed to ascertain whether the associations found between Cd and PSA levels are biologically important or are merely factors to be considered when interpreting PSA results clinically. (Environmental Exposure to Trace Elements and Prostate Cancer in Three New Zealand Ethnic Groups 2005)
Zinc finger proteins "are thought to be involved in both normal and abnormal cellular proliferation and differentiation."(OMIM: ZINC FINGER PROTEIN 143; ZNF143) Many transcription factors can activate the initiation of DNA replication, a process which crucial in the embryo but can go awry as the body ages.
Researchers at the Linus Pauling Institute at Oregon State University acknowledge the mixed, inconclusive evidence on zinc and prostate cancer. They say:
The role of zinc in cancer has received increasing attention for several reasons. The link between zinc deficiency and cancer has now been established by human, animal, and cell culture studies. We also know that zinc status is compromised in cancer patients compared to healthy people. Oxidative DNA damage and chromosome breaks have been reported in animals fed a zinc-deficient diet. In rats, dietary zinc deficiency causes an increased susceptibility to tumor development when the rats are exposed to carcinogens.
Zinc also appears to play an important role in maintaining prostate health, but the precise function of zinc in the prostate is unknown. We are especially interested in how zinc deficiency or supplementation may influence the development of prostate cancer . . . . The normal human prostate accumulates the highest level of zinc of any soft tissue in the body, but we don’t know why. However, cancerous prostates have much less zinc than normal prostates, and several studies have implicated impaired zinc status in the development and progression of prostate malignancy. There is also some evidence that increased dietary zinc is associated with a decrease in the incidence of prostate cancer. We have shown in various cell types that changes in intracellular zinc dramatically affects DNA damage and repair, and, hence, the risk of cancer. It is possible that dietary zinc deficiency will increase a man’s risk for oxidative DNA damage in prostate cells. Zinc supplementation strategies may not only aid in the prevention of cancer, but could also play an important role in limiting its malignancy. As an antioxidant and a component of many DNA repair proteins, zinc plays an important role in protecting DNA from damage. Zinc also functions as an anti-inflammatory agent and can promote programmed cell death, or apoptosis. Thus, zinc supplementation has the potential to target multiple points of the carcinogenesis cascade.
The efficacy of zinc supplements in preventing prostate cancer is controversial. Although several studies have shown that high cellular zinc levels inhibit prostate cancer cell growth, a recent epidemiological study showed an increased risk for prostate cancer in men who took high-dose zinc supplements. Increased cancer risk was seen with very high dose (over 100 mg/day) or long-term (more than 10 years) zinc supplement use. The current tolerable upper intake level for zinc is 40 mg/day, established by the U.S. Institute of Medicine. Thus, it is possible that the subjects in the epidemiological study could have been in the toxic range of zinc intake. As with most therapeutics, higher doses do not always equate with an increase in efficacy. (Zinc and Prostate Cancer
Emily Ho, Ph.D., LPI Principal Investigator
Michelle Yan, OSU Graduate Student, 2005)