الملخص
Background: Africans have breast cancer expressions different from Caucasians. Interactions between oestradiol (E2 ), adiposity and thyroid hormones in breast cancer development have been reported but controversial. The study was designed to investigate the relationships among thyroid hormones, E2 and adiposity in Nigerian pre and postmenopausal women with breast cancer (pre cases and post cases respectively).
Methods: One hundred and sixty nine non-pregnant women aged 48.3±1.3 years were recruited for this study. They comprised of 85 histologically confirmed breast cancer patients (pre-therapy) matched with 84 apparently healthy women without breast cancer (controls) according to age and menstrual phase. Anthropometry was obtained by standard methods. Blood (10ml) was obtained from participants for determination of free thyroxine (fT4 ), free triiodothyronine and thyroid stimulating hormone (TSH) by enzyme immunoassay (EIA). Data analysed by chi-square, student’s t-test and multiple regression were significant at p <0.05.
Results: 16 (29.63%), 18 (33.96%); 12 (22.22%), 4 (7.55%) pre cases and controls were overweight and obese respectively. 12 (38.71%), 15(48.39%); 8 (25.81%), 4 (12.90%) post cases and controls were
overweight and obese respectively. The fT4 was significantly higher in pre and postmenopausal cases than controls (p<0.05). Only waist circumference had inverse relationships with TSH in both pre cases and post cases (â=-8.790, p=0.005). E2 was elevated in post cases only (p<0.05) but had no relationship with any of the thyroid hormones in all groups.
Conclusion: Altered adiposity and subclinical hyperthyroidism may be associated with breast cancer. Weight control and thyroid hormone testing may improve associated morbidity and mortality.
Keywords: Thyroid hormones, oestrogen, adiposity, breast cancer, anthropometry, menstrual status.
Résumé
Contexte: Les Africains ont des expressions de cancer du sein différentes des Caucasiens. Des interactions entre l’œstradiol (E2 ), l’adiposité et les hormones thyroïdiennes dans le développement du cancer du sein ont été rapportées mais controversées. L’étude a été conçue pour étudier les relations entre les hormones thyroïdiennes, l’E2 et l’adiposité chez les femmes nigérianes pré et post-ménopausées atteintes d’un cancer du sein (pré-cas et post-cas respectivement).
Méthodes: Cent soixante-neuf femmes non enceintes âgées de 48,3 ± 1,3 ans ont été recrutés pour cette étude. Ils comprenaient 85 patientes atteintes d’un cancer du sein confirmées histologiquement (préthérapie) assorties avec 84 femmes apparemment en bonne santé sans cancer du sein (témoins) en fonction de l’âge et de la phase menstruelle. L’anthropométrie a été obtenue par des méthodes standard. Du sang (10 ml) a été prélevé sur les participants pour la détermination de la thyroxine libre (fT4 ), de la triodothyronine libre et de la thyréostimuline (TSH) par immunodosage enzymatique (EIA). Les données analysées par le chi-carré, le test t d’élève et la régression multiple étaient significatives à p <0,05.
Résultats: 16 (29,63%), 18 (33,96%); 12 (22,22%), 4 (7,55%) pré -cas et les contrôles étaient en surpoids et obèses respectivement. 12 (38,71%), 15 (48,39%); 8 (25,81%), 4 (12,90%) post-cas et les contrôles étaient en surpoids et obès es respectivement. Le fT4 était significativement plus élevé dans les cas pré et post ménopausiques que chez les témoins (p <0,05). Seul la circonférence de la taille avait des relations inverses avec la TSH dans les deux cas pré-cas et post-cas (β = -8,790, p = 0,005). L’E2 était élevée dans les post-cas seulement (p <0,05) mais n’avait aucun lien avec les hormones thyroïdiennes dans tous les groupes.
Conclusion: Une altération de l’adiposité et une hyperthyroïdie sub -clinique peuvent être associées au cancer du sein. Le contrôle du poids et le test des hormones thyroïdiennes peuvent améliorer la morbidité et la mortalité associées.
Mots-clés: Hormones thyroïdiennes, œstrogène, adiposité, cancer du sein, anthropométrie, état menstruel.
Correspondence: Dr. O.O. Ajayi, Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria. E-mail:olufemal01@yahoo.co.uk
المراجع
Wang B, Mi M, Wang J et al. Does the increase of endogenous steroid hormone levels also affect breast cancer risk in Chinese women? A case-control study in Chongqing, China. Intl J Cancer. 2009; 124: 1892-1899.
Ajayi OO, Charles-Davies MA, Anetor JI and Ademola Y. 2017. Endocrine Disruptors-Arsenic, cadmium and lead in pre and postmenopausal black women with breast cancer Afr J Med Med Sci (in press).
Lai LC. Role of steroid hormones and growth factors in breast cancer. Clin Chem Lab Med. 2002; 10: 969-974
Ajayi OO, Charles-Davies MA, Anetor JI and Ademola AF. Sex Hormones, Oestrogen Receptor, Progesterone Receptor and Human Epithelial Receptor 2 Expressions in Pre and Postmenopausal Sub-Saharan African Women with Breast Cancer. J Cancer Tumor Int’l. 2016; 3(4): 1-11
Neville MC, McFadden TB and Forsyth I. Hormonal regulation of mammary differentiation and milk secretion. J Mam Gland Biol Neoplas. 2002; 1: 49-66
Turken O, NarIn Y, DemIrbas S, Onde ME, Sayan O and Kandemir EG. Breast cancer in association with thyroid disorders. Breast Cancer Res. 2003; 5: R110-R113.
Ali A, Mir MR, Bashir S and Hassan T. Impact of Serum Thyroid Hormones and Estrogen Status on the Risk of Breast Cancer in Kashmiri Women. J Cell Sci and Therap. 2011; 2(4): 113-115
Bello F and Bakari AG. Hypothyroidism in adults: A review and recent advances in management. J Diabetes and Endocrinol. 2012; 3(5): 57-69.
Krassas GE, Poppe K and Glinoer D. Thyroid Function and Human Reproductive Health. Endocriol Rev. 2010; 31: 702-755.
Saraiva PP, Figueiredo NB, Padovani CR, Brentani MM and Nogueir CR. Profile of thyroid hormones in breast cancer patients. Brazil J Med and Biol Res. 2005; 38: 761-765.
Gogas J, Kouskos E, Tseleni-Balafouta S et al. Autoimmune thyroid disease in women with breast carcinoma. Europ J Surg Oncol. 2001; 27: 626-630.
Takatani O, Okumoto T, Kosano H, Nishida M, Hiraide H and Tamakuma S. Relationship between the levels of serum thyroid hormones or estrogen status and the risk of breast cancer genesis in Japanese woman. Cancer Res. 1989; 49: 3109-3112.
Goldman MB. Thyroid diseases and breast cancer. Epidemiol Revs. 1990; 12: 16-28.
Cengiz O, Bozkurt B, Unal B et al. The relationship between prognostic factors of breast cancer and thyroid disorders in Turkish women. J Surg Oncol. 2004; 870: 19-25.
Martinez L, Castilla JA, Gil T et al. Thyroid hormones in fibrocystic breast disease. Europ J Endocrinol. 1995; 6: 673-676.
Shao Z, Sheikh MS, Rishi AH et al. Thyroid hormone enhancement of estradiol stimulation of breast carcinoma proliferation. Exp Cell Res. 1995; 218: 1-8.
Dinda S, Sanchez A and Moudgil V. Estrogen-like effects of thyroid hormone on the regulation of tumor suppressor proteins, p53 and retinoblastoma, in breast cancer cells. Oncogene. 2002; 21: 761-768.
Nogueira CR and Brentani MM. Triiodothyronine mimics the effects of estrogen in breast cancer cell lines. J Steroid Biochem and Mol Biol. 1996; 59: 271-279.
Golden SH, Robinson KA, Saldanha I, Anton B and Ladenson PW. Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab. 2009; 94: 1853–1878
Kokkoris P and Pi-Sunyer FX. Obesity and endocrine disease. Endocrinol Metab Clin North Am. 2003; 32: 895–914
Biondi B. Thyroid and Obesity; An intriguing relationship. JCEM. 2010; 95(8) doi: http://dx.doi.org/10.1210/jc.2010-1245
Menendez C, Baldelli R, Camina JP et al. TSH stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol. 2003; 176: 7-12.
Dalamaga M, Chou SH, Shields K et al. Leptin at the intersection of neuroendocrinology and metabolism: current evidence and therapeutic perspectives. Cell Metab. 2013; 18: 29-42
Hoogwerf BJ and Nuttall FQ. Long-term weight regulation in treated hyperthyroid and hypothyroid subjects. Am J Med. 1984; 76: 963–970
Asvold BO, Bjoro T and Vatten LJ. Association of serum TSH with high body mass differs between smokers and never-smokers. J Clin Endocrinol Metab. 2009; 94: 5023–5027 jc.2009-1180
Knudsen N, Laurberg P, Rasmussen LB et al. Small difference in thyroid function may be important for BMI and the occurrence of obesity in the population. J Clin Endocrinol Metab. 2005; 90(7): 4019-4024
Fox CS, Pencina MJ, D’Agostino RB et al. Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample. Arch Intern Med. 2008; 168: 587–592
Ajayi OO, Charles-Davies MA, Anetor JI and Ademola Y. Serum polychlorinated biphenyls and bisphenol-A levels in Nigerian women with breast cancer. Arch Basic Appl Med. 2014; 2: 71-75.
Mourouzis I, Politi E and Pantos C. Thyroid hormone and tissue repair: new tricks for an old hormone. J Thyroid Res. 2013; doi; 10.1155/2013/312104.312104.
Mourouzis I, Tzovaras A, Armonis B et al. Are thyroid hormones and tumour cell proliferation in human breast cancer positive for HER2 associated? Int’l J Endocrinol. 2015; doi: 10.1155/2015/765406
Pallud S, Ramauge M and Gavaret J-M. Regulation of type 3 iodothyronine deiodinase expression in cultured rat astrocyte: role of Erk cascade. Endocrinol. 1999; 140(6): 2917-2923
Casula S and Bianco AC. Thyroid hormone deiodinases and cancer. Frontiers in Endocrinol. 2012; 74(3). doi; 10.3389/fendo.2012.00074
Smyth PP. The thyroid and breast cancer: a significant association? Annals of Med. 1997; 29: 189-191.
Sarlis NJ, Gourgiotis L, Pucino F and Tolis GJ. Lack of association between Hashimoto thyroiditis and breast cancer: a quantitative research hypothesis. Hormones. 2002; 1:35-41.
Tosovic A, Becker C, Bondeson A-G, Ericsson U-B, Malm J and Manjer J. Prospectively measured thyroid hormone and thyroid peroxidase antibodies in relation to breast cancer risk. Int’l J Cancer. 2012; 131(9): 2126-2133.
Guigon CJ, Kim DW, Willingham MC and Cheng SY. Mutation of thyroid receptor-beta in mice predisposes to the development of mammary tumours. Oncogene. 2011; 30(30):3381-3390
Milionis A and Milionis C. Correlation between body mass index and thyroid function in euthyroid individuals in Greece. ISRN Biomarkers. 2013; Article ID: 651494, 7 pages
Fabian UA, Charles-Davies MA, Fasanmade AA et al. Sex hormones and their relationship with leptin and cardiovascular risk factors in pre and post menopausal Nigerian women with metabolic syndrome. Cardiol Angiol: An Int’l Journal. 2015; 3(3):149-156
Tworoger SS, Eliassen AH and Kelesidis T. Plasma adiponectin concentration and risk of incident breast cancer. J Clin Endocrinol and Metab. 2007; 92:1510-1516.
Mantovani A. Cancer: inflaming metastasis. Nature. 2009; 457: 36-37
Hanahan D and Weinberg RA. The hallmarks of cancer. Cell. 2000; 100: 57-70.
Rutkowski JM, Davis KE and Scherer E. Mechanisms of obesity and related pathologies. The macro and microcirculation of adipose tissue. FEBS. 2009; 276(20):5738-5746
Mullur R, Liu Y-Y and Bren G A. Thyroid Hormone Regulation of Metabolism. Physiol Rev. 2014; 94(2): 355–382
Al-Adsani H, Hoffer LJ and Silva JE. Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement. J Clin Endocrinol Metab. 1997; 82: 1118–1125
Makepeace AE, Bremner AP, O’Leary P et al. Significant inverse relationship between serum free T4 concentration and body mass index in euthyroid subjects: differences between smokers and non smokers. Clin Endocrinol (Oxf). 2008; 69: 648–652
Alevizaki M, Saltiki K, Voidonikola P, Mantzou E, Papamichael C and Stamatelopoulos K. Free thyroxine is an independent predictor of subcutaneous fat in euthyroid individuals. Eur J Endocrinol. 2009; 161: 459–465
Mehran L, Amouzegar A, Tohidi M, Moayedi M and Azizi F. Serum free thyroxine concentration is associated with metabolic syndrome in euthyroid subjects. Thyroid. 2014 24(11):1566-1574.