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Page 2 of 15                         Zaichick et al. J Cancer Metastasis Treat 2018;4:60  I  http://dx.doi.org/10.20517/2394-4722.2018.52

               INTRODUCTION
               Thyroid cancer (TC) is the most common endocrine malignancy. TC incidence has dramatically increased
                                 [1]
               in the recent decades . During the same period no other cancer has increased as much as TC. With the
                                                                                                    [2-4]
               worldwide increase in the incidence of TC, it has become the fifth most common cancer in women . In
               some countries, the incidence of TC has increased extremely fast, and it has been the most common cancer
                              [5]
               over the last years .
               Although the etiology of TC is unknown, several risk factors including deficiency or excess of such
               micronutrient as I have been well identified [6-17] . It was also reported that the incidence of TC and mortality
               from this disease increases progressively with advancing age [18,19] . For example, a 37-fold increase in hazard
               ratio from age < 40 years to age > 70 years was shown in the study of 3,664 TC patients that received surgery
                                                                                               [19]
               and adjuvant treatment at Memorial Sloan Kettering Cancer Center from the years 1985 to 2010 .
               Besides I involved in thyroid function, other trace elements have also 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
                                                                             [20]
               trace elements depend on tissue-specific need or tolerance, respectively . Excessive accumulation or an
               imbalance of the trace elements may disturb the cell functions and may result in cellular degeneration, death
               or malignant transformation [20-22] .

               In our previous study a significant positive correlation between age and some chemical element contents
               in the thyroid was observed [23-28] . It was concluded that an age-dependent excess of intra-thyroidal I and
               Zn concentration is probably one of the factors acting in both initiation and promotion stages of thyroid
               carcinogenesis [9,24,25] , as it was earlier shown by us for I in thyroid and for Zn in prostate gland [29-34] .
               Moreover, it seems fair to suppose that besides I and Zn,many other chemical elementsalso play arolein the
               pathophysiology of the thyroid.


               This work had two aims. The first was to assess the Al, B, Ba, Br, Ca, Cl, Cu, Fe, I, K, Li, Mg, Mn, Na, P, S,
               Si, Sr, V, and Zn mass fraction contents in TC tissue using a combination of non-destructive and destructive
               methods: instrumental neutron activation analysis with high resolution spectrometry of short-lived
               radionuclides (INAA-SLR) and inductively coupled plasma atomic emission spectrometry, respectively. The
               second aim was to compare the levels of chemical elements in the malignant thyroid with those in intact
               (normal) gland of apparently healthy persons.


               METHODS
               All patients suffering from TC (n = 41, mean age Mean ± SD was 46 ± 15 years, range 16-75) were hospitalized
               in the Head and Neck Department of the Medical Radiological Research Centre. Thick-needle puncture
               biopsy of suspicious nodules of the thyroid was performed for every patient, to permit morphological study
               of thyroid tissue at these sites and to estimate their chemical element contents. In cases of surgical operated
               patients with TC the specimens of resected materials were also used for morphological and chemical
               investigation. In all cases the diagnosis has been confirmed by clinical and morphological results obtained
               during studies of biopsy and resected materials. Histological conclusions for malignant tumors were: 25
               papillary adenocarcinomas, 8 follicular adenocarcinomas, 7 solid carcinomas, and 1 reticulosarcoma.

               Normal thyroids for the control group samples were removed at necropsy from 105 deceased (mean age 44 ±
               21 years, range 2-87), who had died suddenly. Samples were obtained within 48 h after a sudden death. The
               majority of deaths were due to trauma. A histological examination in the control group was used to control
               the age norm conformity, as well as to confirm the absence of micro-nodules and latent cancer.
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