Abstract
Background: In this paper we examine some of the evidence linking iodine and selenium to breast cancer development. Seaweed is a popular dietary component in Japan and a rich source of both of these essential elements. We hypothesize that this dietary preference may be associated with the low incidence of benign and malignant breast disease in Japanese women. In animal and human studies, iodine administration has been shown to cause regression of both iodine-deficient goiter and benign pathological breast tissue. Iodine, in addition to its incorporation into thyroid hormones, is organified into anti-proliferative iodolipids in the thyroid; such compounds may also play a role in the proliferative control of extrathyroidal tissues. Selenium acts synergistically with iodine. All three mono-deiodinase enzymes are selenium-dependent and are involved in thyroid hormone regulation. In this way selenium status may affect both thyroid hormone homeostasis and iodine availability.
Conclusion: Although there is suggestive evidence for a preventive role for iodine and selenium in breast cancer, rigorous retrospective and prospective studies are needed to confirm this hypothesis.
Similar content being viewed by others
References
Bailar JC, Gornik HL (1997) Cancer undefeated. N Engl J Med 336: 1569–1571.
Loeser AA (1956) Hormones and breast cancer. Lancet ii: 961–962.
Eskin BA (1970) Iodine metabolism and breast cancer. Trans NY Acad Sci 32: 911–947.
Mittra I, Hayward JL (1974) Hypothalamic-pituitary-thyroid axis in breast cancer. Lancet ii: 885–888.
Stadel BV (1976) Dietary iodine and risk of breast, endometrial, and ovarian cancer. Lancet i: 890–891.
Lee SM, Lewis J, Buss DH (1994) Iodine in British foods and diets. Br J Nutr 72: 435–446.
Pennington JAT, Schoen SA (1996) Total Diet Study: estimated dietary intakes of nutritional elements, 1982-1991. Int J Vitam Nutr Res 66: 350–362.
Konno N, Yuri K, Miura K, Kumagai M, Murakami S (1993) Clinical evaluation of the iodide/creatinine ratio of casual urine samples as an index of daily iodide excretion in a population study. Endocr J 40: 163–169.
Cann SA, van Netten C, van Netten JP (1998) Implementation of a study combining progestin treatment with iodine and selenium supplements in advanced breast cancer [Abstract # C-57] AACR/ JCA Fourth Joint Conference.
Hirai K, Noda K, Danbara H (1996) Selenium intake based on representative diets in Japan, 1957 to 1989. Nutr Res 16: 1471–1477.
Rayman MP (1997) Dietary selenium: time to act. Br Med J 314: 387–388.
Plu-Bureau G, Thalabard JC, Sitruk-Ware R, Asselain B, Mauvais-Jarvis P (1992) Cyclical mastalgia as a marker of breast cancer susceptibility: results of a case-control study among French women. Br J Cancer 65: 945–949.
Bruzzi P, Dogliotti L, Naldoni C, et al. (1997) Cohort study of association of risk of breast cancer with cyst type in women with gross cystic disease of the breast. Br Med J 314: 925–928.
Love SM, Gelman RS, Silen W (1982) Fibrocystic “disease” of the breast-a nondisease? N Engl J Med 307: 1010–1014.
Devitt JE (1986) Abandoning fibrocystic disease of the breast: timely end of an era. Can Med Assoc J 134: 217–218.
Wang DY, Fentimen IS (1985) Epidemiology and endocrinology of benign breast disease. Breast Cancer Res Treat 6: 5–36.
Gravelle IH, Bulbrook RD, Wang DY, et al. (1991) A comparison of mammographic parenchymal patterns in premenopausal Japanese and British women. Breast Cancer Res Treat 18 (suppl.): 93–95.
Sasano N, Tateno H, Stemmermann GN (1978) Volume and hyperplastic lesions of breasts of Japanese women in Hawaii and Japan. Prev Med 7: 196–204.
Strum JM (1979) Effect of iodide-deficiency on rat mammary gland. Virchows Arch [B] 30: 209–220.
Eskin BA, Grotkowski CE, Connolly CP, Ghent WR (1995) Different tissue responses for iodine and iodide in rat thyroid and mammary glands. Biol Trace Elem Res 49: 9–19.
Daro AF, Collin HA, Samos FH (1964) The effect of thyroid on cystic mastitis. J Int Coll Surg 41: 58–59.
Estes NC (1981) Mastodynia due to fibrocystic disease of the breast controlled with thyroid hormone. Am J Surg 142: 764–766.
Peters F, Pickardt CR, Breckwoldt M (1985) Thyroid hormones in benign breast disease. Normalization of exaggerated prolactin responsiveness to thyrotropin-releasing hormone. Cancer 56: 1082–1085.
Vishnyakova VV, Muravieva NI (1966) On the treatment of dyshormonal hyperplasia of mammary glands. Vestn Akad Med Nauk SSSR 21: 19–22.
Ghent WR, Eskin BA, Low DA, Hill LP (1993) Iodine replacement in fibrocystic disease of the breast. Can J Surg 36: 453–460.
Parker SL, Tong T, Bolden S, Wingo PA (1997) Cancer statistics, 1997. CA Cancer J Clin 47: 5–27.
Tominaga S, Kuroishi T (1997) An ecological study on diet/ nutrition and cancer in Japan. Int J Cancer 10 (suppl.): 2–6.
Ziegler RG, Hoover RN, Pike MC, et al. (1993) Migration patterns and breast cancer risk in Asian-American women. J Natl Cancer Inst 85: 1819–1827.
Serra Majem LL, Tresserras R, Canela J, Salleras L (1988) Dietary iodine deficiency and breast cancer mortality: an ecological study. Int J Epidemiol 17: 686–687.
Kun J (1989) Prevention and Treatment of Cancer in Traditional Chinese Medicine. Quarry Bay, Hong Kong: Commercial Press, pp. 211–212.
Zhang D-Z (1989) The Treatment of Cancer by Integrated Chinese-Western Medicine. Boulder, CO: Blue Poppy Press, pp. 21–43.
Kato N, Funahashi H, Ando K, Takagi H (1994) Suppressive effect of iodine preparations on proliferation of DMBA-induced breast cancer in rat. J Jpn Soc Cancer Ther 29: 582–588.
Funahashi H, Imai T, Tanaka Y, et al. (1996) Suppressive effect of iodine on DMBA-induced breast tumour growth in the rat. J Surg Oncol 61: 209–213.
Brown-Grant K, Rogers AW (1972) The sites of iodide concentration in the oviduct and the uterus of the rat. J Endocrinol 53: 355–362.
Markopoulos C, Berger U, Wilson P, Gazet J-C, Coombes RC (1988) Oestrogen receptor content of normal breast cells and breast carcinomas throughout the menstrual cycle. Br Med J 296: 1349–1351.
Strum JM, Phelps PC, McAtee MM (1983) Resting human female breast tissue produces iodinated proteins. J Ultrastruct Res 84: 130–139.
Eskin BA, Parker JA, Bassett JG, George DL (1974) Human breast uptake of radioactive iodine. Obstet Gynecol 44: 398–402.
Shah NM, Eskin BA, Krouse TB, Sparks CE (1986) Iodoprotein formation by rat mammary glands during pregnancy and early postpartum period. Proc Soc Exp Biol Med 181: 443–449.
Russo J, Russo IH (1997) Role of differentiation in the pathogenesis and prevention of breast cancer. Endo-Rel Cancer 4: 7–21.
Haagensen CD (1971) Diseases of the Breast. Philadelphia, PA: WB Saunders, pp. 62.
Kelsey JL, Gammon MD, John EM (1993) Reproductive factors and breast cancer. Epidemiol Rev 15: 36–47.
Yoo KY, Tajima K, Kuroishi T, et al. (1992) Independent protective effect of lactation against breast cancer: a case-control study. Am J Epidemiol 135: 726–733.
Ross RK, Yu MC (1994) Breast-feeding and breast cancer. N Engl J Med 330: 1683.
Yang P-S, Yang T-L, Liu C-L, Wu C-W, Shen C-Y (1997) A case-control study of breast cancer in Taiwan-a low-incidence area. Br J Cancer 75: 752–756.
Newcomb PA, Storer BE, Longnecker MP, et al. (1994) Lactation and a reduced risk of premenopausal breast cancer. N Engl J Med 330: 81–87.
Katsouyanni K, Lipworth L, Trichopoulou A, Samoli E, Struver S, Trichopoulous D (1996) A case-control study of lactation and cancer of the breast. Br J Cancer 73: 814–818.
Thomas DB, Noonan EA (1993) Breast cancer and prolonged lactation. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. Int J Epidemiol 22: 619–626.
Michels KB, Willett WC, Rosner BA, et al. (1996) Prospective assessment of breastfeeding and breast cancer incidence among 89 887 women. Lancet 347: 431–436.
London SJ (1994) Breast-feeding and breast cancer. N Engl J Med 330: 1682.
Brown-Grant K (1961) Extrathyroidal iodide concentrating mechanisms. Physiol Rev 41: 189–213.
Taurog A (1996) Hormone synthesis: thyroid iodine metabolism. In: Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text, 7th edn. Philadelphia, PA: Lippincott-Raven, pp. 47–81.
Hintze G, Kobberling J (1992) Treatment of iodine deficient goiter with iodine, levothyroxine or a combination of both. Thyroidology 4: 37–40.
Dugrillon A (1996) Iodolactones and iodoaldehydes-mediators of iodine in thyroid autoregulation. Exp Clin Endocrinol Diabetes 104 (suppl.): 41–45.
Boeynaems JM, Watson JT, Oates JA, Hubbard WC (1981) Iodination of docosahexaenoic acid by lactoperoxidase and thyroid gland in vitro: formation of an iodolactone. Lipids 16: 323–327.
Dugrillon A, Uedelhoven WM, Pisarev MA, Bechter G, Gartner R (1994) Identification of delta-iodolactone in iodide treated human goiter and its inhibitory effect on proliferation of human thyroid follicles. Horm Metab Res 26: 465–469.
Pisarev MA, Krawiec L, Juvenal GJ, et al. (1994) Studies on the goiter inhibiting action of iodolactones. Eur J Pharmacol 258: 33–37.
Takatani O, Okumoto T, Kosano H, Nishida M, Hiraide H, Tamakuma S (1989) Relationship between the levels of serum thyroid hormones or estrogen status and the risk of breast cancer genesis in Japanese women. Cancer Res 49: 3109–3112.
Giani C, Fierabracci P, Bonacci R (1996) Relationship between breast cancer and thyroid disease: relevance of autoimmune thyroid disorders in breast malignancy. J Clin Endocrinol Metab 81: 990–994.
Yokoe T, Iino Y, Takei H, et al. (1996) Relationship between thyroid-pituitary function and response to therapy in patients with recurrent breast cancer. Anticancer Res 16: 2069–2072.
Strain JJ, Bokje E, van't Veer P, et al. (1997) Thyroid hormones and selenium status in breast cancer. Nutr Cancer 27: 48–52.
Goldman MB (1990) Thyroid diseases and breast cancer. Epidemiol Rev 12: 16–28.
Smyth PPA (1993) Thyroid disease and breast cancer. J Endocrinol Invest 16: 396–401.
Smyth PPA, Hertherton AM, O'Carroll D, Smith DF, O'Halloran MJ, O'Donovan DK (1988) Iodine intake in Ireland-an update. Ir J Med Sci 157: 377–379.
Beckett GJ, Nicol F, Rae PWH, Beech S, Guo Y, Arthur VR (1993) Effects of combined iodine and selenium deficiency on thyroid metabolism in rats. Am J Clin Nutr 57 (suppl.): 240–243.
Diplock AT (1993) Indexes of selenium status in human populations. Am J Clin Nutr 57 (suppl.): 256–258.
Olivieri O, Girelli D, Azzini M, et al. (1995) Low selenium status in the elderly influences thyroid hormones. Clin Sci 89: 637–642.
Salvatore D, Bartha T, Harney JW, Larsen PR (1996) Molecular biological and biochemical characterization of the human type 2 selenodeiodinase. Endocrinology 137: 3308–3315.
Contempre B, Dumont JE, Denef J-F, Many M-C (1995) Effects of selenium deficiency on thyroid necrosis, fibrosis and proliferation: a possible role in myxoedematous cretinism. Eur J Endocrinol 133: 99–109.
Hotz CS, Fitzpatrick DW, Trick KD, L'Abbe MR (1997) Dietary iodine and selenium interact to affect thyroid hormone metabolism in rats. J Nutr 127: 1214–1218.
Contempre B, Dumont JE, Ngo B, et al. (1991) Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium. J Clin Endocrinol Metab 73: 213–215.
Contempre B, Duale NL, Dumont JE, et al. (1992) Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population. Clin Endocrinol 36: 579–583.
Hofbauer LC, Spitzweg C, Magerstadt RA, Heufelder AE (1997) Selenium-induced thyroid dysfunction. Postgrad Med J 73: 103–104.
Vernie LN (1984) Selenium in carcinogenesis. Biochim Biophys Acta 738: 203–217.
El-Bayoumy K (1994) Evaluation of chemopreventative agents against breast cancer and proposed strategies for future clinical intervention trials. Carcinogenesis 15: 2395–2420.
Shamberger RJ, Tytko SA, Willis CE (1976) Antioxidants and cancer. Part IV. Selenium and age-adjusted human cancer mortality. Arch Environ Health 31: 231–235.
Schrauzer GN, White DA, Schneider CJ (1977) Cancer mortality correlation studies-III: statistical associations with dietary selenium intakes. Bioinorg Chem 7: 23–34.
Meyer F, Verreault R (1987) Erythrocyte selenium and breast cancer risk. Am J Epidemiol 125: 917–919.
van't Veer P, van der Wielen PJ, Kok FJ, Hermus RJJ, Sturmans F (1990) Selenium in diet, blood, and toenails in relation to breast cancer: a case-control study. Am J Epidemiol 131: 987–994.
Overvad K, Gron P, Langho. O, Tarp U, Foldspang A, Thorling EB (1991) Selenium in human mammary carcinogenesis: a case-referent study. Eur J Cancer Prev 1: 27–30.
Hardell L, Danell M, Angqvist C-A, et al. (1993) Levels of selenium in plasma and glutathione peroxidase in erythrocytes and the risk of breast cancer. Biol Trace Elem Res 36: 99–108.
Qi X-Y, Zhang A-Y, Wu G-L, Pang W-Z (1994) The association between breast cancer and diet and other factors. Asia Pac J Public Health 7: 98–104.
van't Veer P, Strain JJ, Fernandez-Crehuet J, et al. (1996) Tissue antioxidants and postmenopausal breast cancer: the European Community Multicentre Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast (EURAMIC). Cancer Epidemiol Biomarkers Prev 5: 441–447.
van Noord PAH, Collette HJA, Maas MJ, de Waard F (1987) Selenium levels in nails of premenopausal breast cancer patients assessed prediagnostically in a cohort-nested case-referent study among women screened in the DOM project. Int J Epidemiol 16: 318–322.
Coates RJ, Weiss NS, Daling JR, Morris JS, Labbe RF (1988) Serum levels of selenium and retinol and the subsequent risk of cancer. Am J Epidemiol 128: 515–523.
Hunter DJ, Morris JS, Stampfer MJ, Colditz GA, Speizer FE, Willett WC (1990) A prospective study of selenium status and breast cancer risk. JAMA 264: 1128–1131.
Knekt P, Aromaa A, Alfthan G, et al. (1990) Serum selenium and subsequent risk of cancer among Finnish men and women. J Natl Cancer Inst 82: 864–868.
Overvad K, Wang DY, Olsen J, et al. (1991) Selenium in human mammary carcinogenesis: a case-cohort study. Eur J Cancer 27: 900–902.
van den Brandt PA, Goldbohm RA, van't Veer P, et al. (1994) Toenail selenium levels and the risk of breast cancer. Am J Epidemiol 140: 20–26.
Dorgan JF, Sowell A, Swanson CA, et al. (1998) Relationships of serum carotenoids, retinol, a-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control 9: 89–97.
Hintze G, Burghardt U, Baumert J, Windeler J, Kobberling J (1991) Prevalence of thyroid dysfunction in elderly subjects from the general population in an iodine deficiency area. Aging 3: 325–331.
Weaver DK, Nishiyama RH, Batsakis JG (1976) Iodine induced thyroid disease. Ann Clin Lab Sci 6: 545–550.
Ishizuki Y, Yamauchi K, Miura Y (1989) Transient thyrotoxicosis induced by Japanese kombu. Nippon Naibunpi Gakkai Zasshi 65: 91–98.
Konno N, Makita H, Yuri K, Iizuka N, Kawasaki K (1994) Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab 78: 393–397.
Katamine S, Mamiya Y, Sekimoto K, et al. (1987) Differences in bioavailability of iodine among iodine-rich foods and food colors. Nutr Rep Int 35: 289–297.
Valeix P, Zarebska M, Preziosi P, Galan P, Pelletier B, Hercberg S (1999) Iodine deficiency in France. Lancet 353: 1766–1767.
Longnecker MP, Stram DO, Taylor PR, et al. (1996) Use of selenium concentration in whole blood, serum, toenails, or urine as a surrogate measure of selenium intake. Epidemiology 7: 384–390.
Sundstrom H, Ylikorkala O, Kappila A (1986) Serum selenium and thromboxane in patients with gynaecological cancer. Carcinogenesis 7: 1051–1052.
Goodman MT, Wilkens LR, Hankin JH, Li-Ching L, Wu AH, Kolonel LN (1997) Association of soy and fiber consumption with the rise of endometrial cancer. Am J Epidemiol 146: 294–306.
Key TJA, Silcocks PB, Davey GK, Appleby PN, Bishop DT (1997) A case-control study of diet and prostate cancer. Br J Cancer 76: 678–687.
Clark LC, Dalkin B, Krongrad A, et al. (1998) Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol 81: 730–734.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cann, S.A., van Netten, J.P. & van Netten, C. Hypothesis: Iodine, selenium and the development of breast cancer. Cancer Causes Control 11, 121–127 (2000). https://doi.org/10.1023/A:1008925301459
Issue Date:
DOI: https://doi.org/10.1023/A:1008925301459