Abstract
Background: The involvement of toxic metals in adiposity has been suggested to be contributory to the high incidence of breast cancer, particularly in sub-Saharan Africa. This study is aimed at evaluating serum arsenic, cadmium and lead in relation to adiposity and blood pressure in Nigerian women with breast cancer.
Methodology: The study comprised 85 women newly diagnosed with breast cancer pre-therapy (cases) matched with 84 apparently healthy women without breast cancer (controls) according to age and menstrual phase. Arsenic (As), cadmium (Cd) and Lead (Pb) levels were determined by atomic absorption spectrophotometry. Blood pressure and anthropometry were determined by standard methods. Data analysed by Student’s t-test and Pearson correlation coefficient were considered statistically significant at p<0.05.
Results: Cd and Pb levels were significantly higher in cases, compared with controls (p<0.05). Waist circumference (WC), hip circumference (HC), weight, height, waist hip ratio (WHR), waist height ratio (WHtR) were significantly higher in cases compared with controls (p<0.05). Cadmium positively correlated with diastolic blood pressure while FT4 inversely correlated with arsenic in the cases (p<0.05).
Conclusion: Observations in this study suggest the involvement of these toxic metals in adiposity which could be involved in breast carcinogenesis.
Keywords: Lead, cadmium, arsenic, breast cancer, blood pressure, adiposity.
Résumé
Contexte: L’implication des métaux toxiques dans l’adiposité a contribué à la forte incidence du cancer du sein, en particulier en Afrique subsaharienne. Cette étude avisée à évaluer l’arsenic sérique, le cadmium et le plomb par rapport à l’adiposité et à la tension artérielle chez des femmes nigérianes atteintes de cancer du sein.
Méthodologie: l’étude comprenait 85 femmes nouvellement diagnostiquées avec le cancer du sein, prétraitement (cas) égalée avec 84 femmes apparemment en bonne santé sans cancer du sein (témoins) selon l’âge et la phase menstruelle. Les niveaux d’arsenic (As), de cadmium (Cd) et de plomb (Pb) ont été déterminés par la spectrophotométrie d’absorption atomique. La pression artérielle et l’anthropométrie ont été déterminées par des méthodes standard. Les données analysées par le test t d’étudiant et le coefficient de corrélation de Pearson ont été jugées statistiquement significatives à p <0,05.
Résultats: Les niveaux de Cd et de Pb étaient significativement plus élevés dans les cas, par rapport aux témoins (p <0,05). La circonférence de la taille (CT), la circonférence de la hanche (CH), le poids, la hauteur, le rapport de la taille et de la hanche (RTH), le rapport de taille de la hauteur (RTHt) étaient significativement plus élevés dans les cas comparés aux témoins (p <0,05). Le cadmium s’est corrélé positivement avec la pression sanguine diastolique tandis que le FT4 était inversement corrélé avec l’arsenic dans les cas (p <0,05).
Conclusion: Les observations dans cette étude suggèrent l’implication de ces métaux toxiques dans l’adiposité qui pourraient être impliqués dans la carcinogenèse du sein.
Mots-clés: Plomb, cadmium, arsenic, cancer du sein, pression sanguine, adiposité.
Correspondence: Dr. Olulope A. Ajayi, Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria. Email: olufemi01@yahoo.co.uk
References
Ho CCK, Rohaizak M, Zulkifli SZ et al. Serum sex hormone levels in pre- and postmenopausal breast cancer patients. Singapore Medical Journal 2009; 50(5):513-518.
Adebamowo CA, Ogundiran TO, Adenipekun AA et al. Waist-hip ratio and breast cancer risk in urbanized Nigerian women. Breast Cancer Research. 2003; 5:18-24.
Ragab AR, Farouk O, Afify MM et al. The Role of Oxidative Stress in Carcinogenesis Induced By Metals in Breast Cancer Egyptian Females Sample at Dakahlia Governorate. Journal of Environmental Analysis and Toxicology. 2014; 4:207.
Anetor JI, Akingbola TS, Adeniyi FAA and Taylor GO. Decreased total and ionized calcium levels and haematological indices in occupational lead exposure as evidence of the endocrine disruptive effect of lead. Indian Journal of Occupational and Environmental Medicine. 2005; 9(1):15-21
Carpenter DO, DeCaprio AP, O’Hehir D et al. Polychlorinated biphenyls in the serum of the Siberian Yupik people from St Lawrence Island, Alaska. International Journal of Circumpolar Health. 2005. 64(4):322-335
Antila E, Mussalo-Rauhamaa H, Kantola M et al. Association of cadmium with human breast cancer. Science of the Total Environment. 1996; 186(3):251-256.
Kang JH, Kondo F and Katayama Y. Human exposure to bisphenol-A. Toxicology. 2006. 226 (2/3):79–89.
Rossner P Jr, Gammon MD, Terry MB et al. Relationship between urinary 15-F2t-Isoprostane and 8-Oxodeoxyguanosine levels and breast cancer risk. Cancer Epidemiology Biomarkers Previews. 2006; 15(4):639-644.
Charles-Davies MA, Arinola OG, Fasanmade AA et al. Indices of metabolic syndrome in 534 apparently healthy Nigerian traders. Journal of US-China Medical Science. 2012; 9(2):91-100.
Donohoe CL, Doyle SL and Reynolds JV. Visceral adiposity, insulin resistance and cancer risk. Diabetology and Metabolic Syndrome. 2011; 3(12). PMC 3145556
Bartolome B, Cordoba S, Nieto S et al. Acute arsenic poisoning, clinical and histopathologic features. British Journal of Dermatology. 1999; 141:1106-1109.
Tseng CH, Huang YK, Huang YL et al. Arsenic exposure, urinary arsenic speciation, and peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan. Toxicology and Applied Pharmacology. 2005; 206(3):299-308
Frumklin MC, Wang J and Stetz TA. Structure of the replicating complex of the pol alpha family DNA polymerase. Cell. 2001; 105(5): 657-667.
Davey JC, Bodwell JE, Gosse JA and Hamilton JW. Arsenic as an endocrine disruptor: effects of arsenic on oestrogen receptor-mediated gene expression in vivo and in cell culture. Toxicol Sci. 2007; 98:75-86
Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Arsenic- ATSDR. U.S. Department of Health and Human Services, Public Health Services, ATSDR, Atlanta, Georgia. 2005.
McLaughlin M J, Palmer L T, Tiller K G, et al. Increased soil salinity causes elevated cadmium concentration in field grown potato tubes. Journal of Environmental Quality. 1997; 26:1644 1699.
.Alissa EM and Ferns GA. Heavy metal poisoning and cardiovascular disease. Journal of Toxicology. Vol 2011 (2011). Article id 870125, 21 pages
Sivrikaya A, Menevse E, Altýntepe L and Tiftik AM. The Relations between Levels of Cadmium and Thyroid Parameters in Hemodialysis Patients. Journal of Clinical and Analytical Medicine. 2013; 4.1: 1-4.
Tekin D, Kayaalti Z, Aliyev V and Soylemezoglu T. The effects of metallothionein 2A polymorphism on placental cadmium accumulation: Is metallothionein a modifiying factor in transfer of micronutrients to the fetus? Journal of Applied Toxicology. 2012; 32: 270-275.
Reeves PG and Chaney RL. Bioavailability as an issue in risk assessment and management of food cadmium: A review. Science of the Total Environment. 2008; 398:13-19
Strumylaite L, Boqusevicius A, Abdrachmanovas O et al. Cadmium concentration in biological media of breast cancer patients. 2011;125(2): 511-517
Rothenberg SJ, Karchmer S, Schnaas L et al. Changes in serial blood lead levels during pregnancy. Environmental Health Perspectives. 1994; 102(10):876-880.
Kessler R. Lead-based decorative paints; where are they still sold and why? Environmental Health Perspectives. 2014; 122(4): 96-103.
Steenland K, Selevan S and Landrigan P. The mortality of lead smelter workers. An update. American Journal of Public Health. 1992; 82:1641-1644.
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. International Journal of Cancer. 2009; 124: 1892-1899.
Ajayi Olulope O, Charles-Davies Mabel A, Anetor John I and Ademola Yinka. Serum polychlorinated biphenyls and bisphenol-A levels in Nigerian women with breast cancer. Archive of Basic and Applied Medicine. 2014; 2:71-75.
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. Journal of Cancer and Tumor International. 2016; 3(4):1-11.
Umoh U, Charles-Davies MA and Adeleye J. Serum testosterone and lipids in relation to sexual dysfunction in males with metabolic syndrome and type 2 diabetes mellitus. Int’l J.Med Med Sci. 2010; 2(12): 402-412
Jarup L and Akesson A. Current status of cadmium as an environmental health problem. Toxicology and Applied Pharmacology. 2009; 238:201-208.
Siewt CL, Gengler B, Vegas E et al. Cadmium promotes breast cancer cell proliferation by potentiating the interaction between ER alpha and c-jun. Molecular Endocrinology. 2010; 24:981-992.
Stoica A, Katzenellenbogen BS and Martin MB. Activation of estrogen receptor-alpha by the heavy metal cadmium. Molecular Endocrinology. 2000b; 14:545–553.
Johnson MD, Kenney N, Stoica A et al. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. National Medicine. 2003; 9:1081-1084.
Zhou X, Sun H, Ellen TP, Chen H and Costa, M. Arsenite alters global histone H3 methylation. Carcinogenesis. 2008; 29:1831-1836
Florea AM and Busselberg D. Metals and breast cancer; risk factors or healing agents? Journal of Toxicology. 2011; 1-8
Wong O and Harris F. Cancer mortality study of employees at lead battery plants and lead smelters, 1947-1995. American Journal of Industrial Medicine. 2000; 38:255-270.
Martin MB, Reiter R, Pham T et al. Estrogen-like activity of metals in MCF-7 breast cancer cells. Endocrinology. 2003; 144(6):2425-2436.
Siddiqui MK, Jyoti- Singh S, Mehrotra PK et al. Comparison of some trace elements concentration in blood, tumour free breast and tumour tissues of women with benign and malignant breast lesions, an Indian study. Environmental Interactions. 2006; 32(5):630-637
Lutzen A, Liberti SE and Rasmussen LJ. Cadmium inhibits human DNA mismatch repair in vivo. Biochemical and Biophysical Research Communication. 2004; 321(1):21-25.
Ying S, Myers K, Bottomley S et al. BRCA2-dependent homologous recombination is required for repair of Arsenite-induced replication lesions in mammalian cells. Nucleic Acid Research. 2009; 37(15): 5103-5113.
Kaltreider RC, Pesce CA, Ihnat MA et al. Differential effects of arsenic (III) and chromium (VI) on nuclear transcription factor binding. Molecular Carcinogenesis. 1999; 25(3):219-229.
Zhao CQ, Young MR, Diwan BA, Coogan TP and Waalkes MP. Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proceedings of National Academy of Science USA.1997; 94: 10907-10912
Verma M and Srivastava S. Epigenetics in cancer: implications for early detection and prevention. Lancet Oncology. 2002; 3: 755-763
Vaissiere T, Sawan C and Herceg Z. Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutation Research. 2008; 659:40-48
Vo An. T. and Millis RM. Epigenetics and breast cancers. Obstetrics and Gynaecology International. 2012; Article ID;602720, 10 pages
Pogrinby IP and Rusyn I. Environmental toxicants, epigenetics and cancer. Advanced Experimental Medical Biology. 2013; 754: 215-232
Lahmann PH, Hoffmann K, Allen N et al. Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). International Journal of Cancer. 2004; 111(5):762-771.
Ogundiran TO, Huo D, Adenipekun A et al. Case-Control Study of Body Size and Breast Cancer Risk in Nigerian Women. American Journal of Epidemiology. 2010; 1-9
Trentham-Dietz A, Newcomb PA, Storer BE, et al. Body size and risk of breast cancer. American Journal of Epidemiology. 1997; 145(11):1011–1019.
Shu XO, Jin F, Dai Q, et al. Association of body size and fat distribution with risk of breast cancer among Chinese women. International Journal of Cancer. 2001; 94(3):449–455.
Lovegrove JA. Obesity, body fat distribution and breast cancer. Nutrition Research Review. 2002; 15.2: 389–412.
Gill T, Chittlebourough, C and Taylor A. Body mass index, waist hip ratio and waist circumference; which measure to classify obesity? Soz Preventivemed. 2003; 48:191-200.
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. Cardiology and Angiology: An International Journal. 2015; 3(3):149-156.
Fagherazzi G, Chabbert-Buffet N, Fabre A, et al. Hip circumference is associated with the risk of premenopausal ER-/PR- breast cancer. Int J Obes (Lond). 2012; 36(3):431-439
Tworoger SS, Eliassen AH and Kelesidis T. Plasma adiponectin concentration and risk of incident breast cancer. Journal of Clinical Endocrinology and Metabolism. 2007; 92:1510-1516.
Rutkowski JM, Davis KE and Scherer PE. Mechanisms of obesity and related pathologies: The macro and microcirculation of adipose tissue. FEBS Journal. 2009; 276(20):5738-5746
Schunkert H, Danser AH, Hense H-W, et al. Effects of estrogen replacement therapy on the rennin angiotensin system in postmeopausal women. Circulation 1997; 95:39-45
Jiang C, Sarrel PM, Poole-Wilson PA and Collins P. Acute effect of 17-beta oestradiol on rabbit coronary artery contractile response to endothelin-1. Am J Physiol 1992; 263: H 271-275
Sharma AM, Homuth V and Luft FC. Hormone replacement therapy and blood pressure in normotensive and hypertensive women. Nephrol Dial Transplant 2001; 16 (5): 888-890.
Gallagher CM and Meliker JR. Blood and Urine Cadmium, Blood Pressure, and Hypertension: A Systematic Review and Meta-analysis. Environ Health Perspect. 2010 Dec; 118(12): 1676–1684
Yoopan N, Watcharasit P, Wongsawatkul O, Piyachaturawat P and Satayavivad J. Attenuation of eNOS expression in cadmium-induced hypertensive rats. Toxicol Lett. 2008 Jan 30; 176(2):157-161.