The incidence and mortality rates for prostate cancer vary widely worldwide. Many believe that lifestyle and diet are the dominant causes for this variation and that sex hormones factor somewhere in between those and molecular and exogenous considerations. Because prostate cancer is considered as an androgen-dependent disease, the role of estrogen largely remains uninvestigated despite evidence suggesting that it plays a key role. In a review appearing in the Journal of Cellular Biochemistry, Carruba examines recent studies of the role of estrogen on human prostate cancer.
The author equates human prostate and breast cancers in a way that they share geographical distribution patterns, risk factors, biomolecular determinants and natural histories. He also maintains that dietary factors and estrogen play key roles in many biological and pathological processes. Epidemiologic evidence presented in the paper notes that migrants from countries with low incidence and mortality rates move to countries with higher incidence and mortality rates show, within a generation, a significant increase in prostate cancer incidence and mortality when compared with peers in their country of origin. The diet and lifestyle factors may effect such changes because of their influence, in particular, on estrogens. In examining the evidence from studies of circulating steroids, the author points out the inconsistent and inconclusive data regarding circulating androgen levels and prostate cancer and suggests that the obvious conclusion is that no cause-and-effect relationship exists. The author observes that hormone levels in target tissues may differ significantly from those in plasma and that, unlike in breast cancer research, only a few preliminary studies have assessed intraprostatic levels of sex hormones. In analyzing the evidence from animal studies, the author notes that only the dog demonstrates an incidence of prostate cancer similar to that of humans and the results of other animal studies, such as those in rats, must be interpreted with caution. Regarding estrogen receptors (ERs), some evidence suggests that variants of ERalpha and ERbeta may modulate estrogen in the target tissues such as prostate. The author concludes that estrogen is a ‘pointed example’ of how a key factor in prostate cancer has been eclipsed by the dominant interest in androgens.