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Page 2 of 9                            Zaichick et al. J Cancer Metastasis Treat 2019;5:48  I  http://dx.doi.org/10.20517/2394-4722.2019.07

               an involvement of these trace elements in etiology and pathogenesis of malignant prostate tumors. It was supposed
               that the differences in Rb and Zn levels in prostatic fluid can be used as tumor markers.


               Keywords: Benign prostatic hyperplasia, prostate cancer, prostatic fluid, trace elements, energy-dispersive X-ray
               fluorescent analysis





               INTRODUCTION
               Prostate cancer (PCa) is the most prevalent nonskin male cancer in many populations, including USA,
               Scandinavia, West European states, Australia, New Zealand, and others . Globally, PCa ranks second in
                                                                             [1,2]
               incidence and the fifth in mortality in men, and represents a substantial public health burden . Although
                                                                                               [1,2]
               the etiology of PCa is unknown, several risk factors including age and diet have been well identified. Thus,
               the risk of having PCa drastically increase with age, being three orders of magnitude higher for the age
               group 40-79 years than for those younger than 39 years . The odds of PCa diagnosis by age 79 years are one
                                                             [3,4]
               in six among countries with a high sociodemographic index.

               Benign prostatic hyperplasia (BPH) is an internationally important health problem of the man, particularly
               in developed countries, and represents the most common urologic disease among of men after the age of
               fifty . Incidence of histological BPH could be over 70% at 60 years old and over 90% at 70 years old . To
                                                                                                    [4,8]
                   [4-7]
               date, we still have no precise knowledge of the biochemical, cellular and molecular processes underlying the
               pathogenesis of BPH. Although the influence of androgens and estrogens has been demonstrated, hormonal
               factors alone may not fully explain BPH development [9,10] .


               Thus, the both PCa and BPH is the very common urologic disease in adult males. Moreover, use systematic
               review methods provide the statistical evidence that the association between PCa and BPH is significant [11,12] .
               BPH can be a cause of an elevated prostate specific antigen level in blood . In these cases it is difficult
                                                                               [13]
               to differentiate BPH from PCa because the findings of imaging modalities like TRUS and conventional
               MR Imaging can mimic those of PCa. Even biopsy doesn’t play promising role in the diagnosis of BPH.
               As a result of this, BPH may be misdiagnosed as a malignant condition and end up in aggressive surgical
               management resulting in increased morbidity. This warrants the need of reliable diagnostic tool which has
               ability not only to diagnose BPH reliably but also to differentiate it from the PCa.


               It was reported that the risk of having PCa and BPH depends on lifestyle and diet, including the intake
               of zinc (Zn) and some other trace elements (TE) [14-18] . TE have essential physiological functions such as
               maintenance and regulation of cell function, gene regulation, activation or inhibition of enzymatic reactions,
               and regulation of membrane function. Essential or toxic (mutagenic, carcinogenic) properties of TE depend
               on tissue-specific need or tolerance, respectively . Excessive accumulation or an imbalance of the TE may
                                                        [19]
               disturb the cell functions and may result in cellular degeneration or death [19-24] .

               In our previous studies a significant involvement of Zn and some other TE in the function of prostate was
               observed [25-39] . Moreover, it was found that intracellular Zn and calcium (Ca) excess is one of the main factors
               in the etiology of prostate cancer [16-18,24,25] . One of the main functions of prostate gland is a production of
               prostatic fluid  with extremely high concentration of Zn and some other chemical elements. The first finding
                           [40]
               of remarkable high level of Zn concentration in human expressed prostatic fluid (EPF) was reported in the
               beginning of 1960s . Analyzing EPF expressed from prostate of 8 apparently healthy men aged 25-55 years it was
                              [41]
               found that Zn concentration varied in range from 300 to 730 mg/L. After this finding several investigators have
               suggested that the measurement of Zn level in EPF may be useful as a marker of prostate secretory function [42,43] .
               It promoted a more detailed study of Zn concentration in EPF of healthy subjects and in those with different
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