The thyroid, hormones, iodine and cancer
anaplastic thyroid carcinoma and medullary thyroid carcinomas are rare. The overall incidence for a relationship between iodine and cancer is poor and. In nature, iodine is a relatively rare element. . Compelling data are emerging that link iodine deficiency to breast cancers and high rates of fibrocystic breast. However, the overall incidence for a relationship between iodine and cancer is poor. It has known that iodine deficiency is associated with fibrocystic breast In , the median urinary iodine concentration was less than μg/L, but since .
Where an association between thyroid disease and breast cancer was shown to exist, hypothyroidism was the most frequently observed finding. In fact, many reports considered hyperthyroidism to be protective against breast cancer because progression of such cancers was more frequently observed when the hyperthyroidism was treated [ 5 ].
The increased frequency of thyroid autoantibodies, TPO antibodies and thyroglobulin antibodies described by Turken and coworkers [ 1 ] in breast cancer patients as compared with control individuals supports earlier findings [ 8 - 11 ]. Such differences were not observed for other autoimmune antibodies [ 9 ]. The use of specific immunoassays for TPO antibodies and thyroglobulin antibodies [ 12 ] revealed an increased prevalence of TPO antibodies in breast cancer.
Although the presence of circulating TPO antibodies in asymptomatic individuals has been implicated as conferring an increased risk for future hypothyroidism [ 13 ], there is no agreement on the significance of its association with breast cancer [ 14 ].
However, no significant association between breast cancer and Hashimoto's thyroiditis was reported in a study from the Mayo Clinic in the USA [ 15 ]. Thus, like other reported associations, the relationship between AITD, iodine intake and breast cancer is far from clear. Equally, there is little agreement on the significance of any published association between a range of thyroid disorders and breast cancer [ 56 ].
The possibility that hypothyroidism might in itself have been beneficial in terms of outcome of breast cancer has been suggested [ 16 ]. Recent reports from our laboratory [ 11 ] have shown that the presence of TPO antibodies is associated with a significant improvement in both disease-free and overall outcome in breast cancer patients, and that the magnitude of this prognostic effect was of a similar order of magnitude to well established prognostic indices for breast cancer such as axillary nodal status or tumour size.
Thus, we have the anomalous situation in which the presence of TPO antibodies, while being associated with breast cancer, also appears to confer prognostic benefits.
A recent review that contained a meta-analysis of published work on breast—thyroid associations [ 14 ] found no significant association between the two disorders and attributed any positive findings of such an association to 'selection or institutional referral bias'.
Iodine and cancer.
This negative finding was immediately followed by communications [ 117 ] reaffirming the association of breast cancer with hypothyroidism and AITD. It is therefore apparent that the argument about breast—thyroid associations is far from resolved. Thyroid antibody related hypothyroidism has been suggested as being associated with a favourable tumour response to such therapies. In a recent report [ 19 ] it was shown in metastatic renal cell carcinoma that the presence of a positive thyroid antibody titre, either pre-existing or cytokine induced, was a highly significant independent prognostic factor.
In the case of thyroid autoantibodies being associated with better disease outcome in breast cancer, renal carcinoma or melanoma, it is possible that the immune response to thyroid and tumour tissue might be similarly regulated in that it might be directed against both tumour and thyroid antigens.
Another possibility is that both tumour and thyroid share the same antigens because expression of the sodium—iodide symporter has been demonstrated in both thyroid and breast tissues [ 20 - 22 ]. One area in which thyroid and breast functions overlap is in the uptake and utilization of iodide. In the thyroid, I- is required for thyroid hormonogenesis whereas in the breast I- is needed in breast milk as a source of neonatal nutrition.
Both organs require a method of oxidizing I- to I2 organification in order to produce iodoproteins [ 2324 ].
The thyroid, iodine and breast cancer
This involves the presence of H2O2 as an oxidizing agent catalyzed by TPO in the thyroid and by lactoperoxidases in the breast.
Apart from the requirement for iodide as a nutrient in breast milk, there is no known role for iodine in the normal or diseased breast. However, a breast requirement for I2 rather than I- has been suggested [ 25 ]. It has been postulated that formation of iodolipids such as iodolactones or iodoaldehydes represents a form of thyroidal autoregulation [ 26 ], which may be the mode of action of iodide inhibition of thyroid function in the Wolff—Chaikoff effect [ 27 - 29 ].
In addition to their role in inhibiting thyroid function, these compounds may act as antiproliferative agents in the thyroid [ 26 ]. This effect seems to require oxidation of I- to I2 because inhibitors of TPO or I- trapping can reverse the inhibitory effect [ 29 ]. It has also been suggested that such inhibitory actions of iodo-compounds on cell proliferation might play a role in the breast [ 3031 ]. Some support for a role for iodine in the human breast is provided by our own findings [ 20 ], which showed that tissue iodine levels were relatively low in patients with breast cancer as compared with normal tissues or benign breast tumours fibroadenomata.
The ability of the breast to express sodium—iodide symporter [ 20 - 22 ] and, at least in lactation, to take up significant amounts of iodide has led to studies of the potential for use of I ablative therapy in breast cancer, analogous to that employed in the treatment of hyperthyroidism or thyroid cancer.
An anticarcinogenic role for iodine in experimental animals was suggested by the work of Funahashi and coworkers [ 33 ], who found that administration of Lugol's iodine or iodine-rich Wakame seaweed to rats treated with the carcinogen dimethyl benzanthracene suppressed the development of mammary tumours. In further studies [ 34 ], the same group demonstrated that seaweed induced apoptosis in human breast cancer cells with greater potency than that of fluorouracil, a chemotherapeutic agent used to treat breast cancer.
This finding led the authors to speculate that 'seaweed may be applicable for prevention of breast cancer'.
Observed association between improved iodine supply and decrease of incidence of stomach cancer could indicate the protective role against stomach cancer of iodine prophylaxis in iodine deficient areas. In the stomach, iodine protects against abnormal growth of bacteria, in which Helicobacter pylori is the most clinically significant. Iodine in the stomach can also deactivate all biological and most chemical poisons Stadel Failure to trigger the apoptosis in gastric cancer cells resulting from decreased iodine might be harmful Gulaboglu et al, Zhang et al have shown that increased intracellular levels of iodine is associated with enhance tumor apoptosis in most of the modified non-small cell lung cancer.
They assessed a nonradioactive approach in the non-small cell lung cancer with retroviral vectors containing NIS and thyroperoxidase TPO genes. They for first time demonstrated that a therapeutic dose of nonradioactive iodide has potent efficacy and high selectivity against lung cancer Zhuang et al, An increased risk of thyroid cancer has been reported in humans with goiter and those living in some iodine-deficient areas of the world Ohshima et al, Studies suggest that a major role of iodine is to prevent the formation of thyroid tumors in humans Ward et al.
Iodine deficiency is also associated with increased risk for thyroid carcinoma in animal models. Mutaku JF and et al have shown anti-proliferative effects of excess iodine on thyroid cells Mutaku et al, To the best of our knowledge this was the first study evaluated the iodine status in Iranian patients diagnosed with a malignancy. However, results of the present study showed severe iodine deficiency in the patients. Therefore, check the status of iodine in normal populations and cancer patients may be crucial.
In addition, we suggest that daily consumption of salt fortified with iodine or other approaches might be an effective strategy for prevention or reduction of malignancies. The Extrathyronine actions of Iodine as antioxidant, apoptotic, and differentiation factor in various tissues. East Mediterr Health J. Medical Alternative Press; Sodium Iodide symporter and the radioiodine treatment of thyroid carcinoma.
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Eighteen years of continuously sustained elimination of iodine deficiency in the Islamic Republic of Iran: Asian Pac J Cancer Prev. Iodine replacement in fibrocystic disease of the breast.
Iodine prophylaxis-the protective factor against stomach cancer in iodine deficient areas. Comparison of iodine contents in gastric cancer and surrounding normal tissues.
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The effect of supraphysiologic levels of iodine on patients with cyclic mastalgia. Ovarian endometriosis cyst with iodine uptake: