Resumen
Introducción: en el desarrollo de cáncer de mama (CaMa), la exposición estrogénica y el aumento de la densidad mamaria (DM) son dos factores determinantes de riesgo.
Objetivo: identificar la asociación entre los polimorfismos XbaI y PvuII del receptor de estrógenos (ER-alfa) con la DM.
Material y métodos: estudio transversal que incluyó 225 pacientes de 40-65 años, sin datos evidentes de cáncer, que se realizaron mastografía de rutina en un departamento de radiología para diagnóstico precoz de CaMa. Se clasificaron en dos grupos: con presencia o ausencia de DM aumentada. Se les tomó muestra sanguínea para extraer DNA y determinar los polimorfismos XbaI y PvuII del gen ER-alfa.
Resultados: 19.1% tuvo peso normal, 37.7% sobrepeso y el 43.2% obesidad. En relación con la DM, 105 tuvieron mama densa (46.7%) y 120 mama no densa (53.3%). La frecuencia de mujeres con mama densa fue inferior en las mujeres posmenopáusicas. En cuanto al tipo de DM, no hubo diferencia significativa entre las frecuencias en los genotipos de PvuII y XbaI. La regresión logística mostró que solo la edad y el índice de masa corporal (IMC) fueron factores determinantes de la DM.
Conclusiones: los genotipos PvuII y XbaI del ER-alfa fueron similares entre las mujeres con mama densa y no densa; en contraste, otros factores se relacionaron con la DM (edad, IMC y estado menopáusico). Por ende, en la práctica clínica se debe enfatizar la relación del IMC con la DM, pues esta representa un factor de riesgo de CaMa.
Abstract
Background: In the development of breast cancer (BC), estrogen exposure and the increase in breast density (BD) are two determinant factors for BC risk.
Objective: To identify the relationship between the XbaI and PvuII polymorphisms in the estrogen receptor (ER-alpha) with BD.
Material and methods: Cross-sectional study which included 225 women, aged 40-65 years, without evident cancer data, who underwent routine mammography for early BC diagnosis in a radiology department. Two groups were formed: women with increased and with normal BD. Participants were genotyped for the XbaI and PvuII polymorphisms.
Results: 19.1% had normal weight, 37.7% overweight, and 43.2% were obese women. In relation to high-risk patterns, 105 women had increased BD and 120 had normal BD (53.3%). The frequency of women with increased BD was also lower in postmenopausal women. Regarding the type of BD, there was no statistically significant difference between frequencies of PvuII and XbaI genotypes. Logistic regressionge and body mass index (BMI) were associated with BD.
Conclusion: PvuII and XbaI ER-alpha genotypes were similar among women with dense and non-dense breasts; differently, other factors were associated with BD (age, BMI and menopausal status). Therefore, emphasis should be placed on clinical practice in the relationship between BMI and BD.
Bray G, Ferlay J. Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
Instituto Nacional de Cancerología. Registro de supervivientes de cáncer. México: INCan; 25 de agosto de 2016 [consultado el 5 de enero de 2017]. Disponible en https:// www.gob.mx/insalud/articulos/registro-de-supervivientes-de-cancer.
Tice J, Cummings S, Smith-Bindman R, Ichikawa L, Barlow W, Kerlikowske K. Using clinical factors and mammographic breast density to estimate breast cancer risk: Development and validation of a new predictive model. Ann Int Med. 2008;148(5):337.
Wolfe J. Breast patterns as an index of risk for developing breast cancer. American J Roentgenol. 1976;126(6):1130-7.
McCormack V. Breast density and parenchymal patterns as markers of breast cancer risk: A meta-analysis. Cancer Epidemiol Biomarkers and Prevention. 2006;15(6):1159-69.
Boyd N, Guo H, Martin L, Sun L, Stone J, Fishell E, et al. Mammographic Density and the Risk and Detection of Breast Cancer. N Engl J Med. 2007;356(3):227-36.
Martin L, Boyd N. Mammographic density. Potential mechanisms of breast cancer risk associated with mammographic density: hypotheses based on epidemiological evidence. Breast Cancer Research. 2008;10(S1).
Grove J, Goodman M, Gilbert F, Mi M. Factors associated with mammographic pattern. British J Radiol. 1985;58(685):21-5.
Clemons M, Goss P. Estrogen and the risk of breast cancer. N England J Med. 2001;344(4):276-85.
Enmark E, Gustafsson J. Oestrogen receptors – an overview. J Int Med. 1999;246(2):133-8.
Cahua-Pablo JÁ, Flores-Alfaro E, Cruz M. Receptor de estrógenos alfa en obesidad y diabetes. Rev Med Inst Mex Seguro Soc. 2016;54(4):521-30.
Anderson T, Heimdal K, Skrede M, Tveit K, Berg K, Barresen A. Oestrogen receptor (ESR) polymorphisms and breast cancer susceptibility. Hum Gen. 1994;94(6):665-70.
Onland-Moret N, van Gils C, Roest M, Grobbee D, Peeters P. The estrogen receptor α gene and breast cancer risk (The Netherlands). Cancer Causes Control. 2005;16(10):1195-202.
Li N, Dong J, Hu Z, Shen H, Dai M. Potentially functional polymorphisms in ESR1 and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2009;121(1):177-84.
Shin A, Kang D, Nishio H, Jin Lee M, Kyung Park S, Kim S, et al. Estrogen receptor alpha gene polymorphisms and breast cancer risk. Breast Cancer Res Treat. 2003;80(1):127-31.
Cai Q, Shu XO, Jin F, Dai Q, Wen W, Cheng JR, et al. Genetic polymorphisms in the estrogen receptor alpha gene and risk of breast cancer: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev. 2003;12(9):853-9.
Schuit S, Oei H, Witteman J, Geurts C, van Meurs J, Nijhuis R, et al. Estrogen Receptor a gene polymorphisms and risk of myocardial infarction. JAMA. 2004;291:2969-77.
Murillo-Ortiz B, PérezLuque EL, Malacara JM. Densidad mamaria y su asociación con el polimorfismo del gen del receptor de estrógenos alfa (ERα) Pvull y Xbal. Ginecol Obstet Mex. 2005;73:229-33.
Warren R. Associations among mammographic density, circulating sex hormones, and polymorphisms in sex hormone metabolism genes in postmenopausal women. Cancer Epidemiol Biomarker Prev. 2006;15(8):1502-8.
Crandall C, Sehl M, Crawford S, Gold E, Habel L, Butler L, et al. Sex steroid metabolism polymorphisms and mammographic density in pre- and early perimenopausal women. Breast Cancer Res. 2009;11(4)R51.
Van Duijnhoven F. Polymorphisms in the estrogen receptor gene and mammographic density. Cancer Epidemiol Biomarkers Prev. 2005;14(11):2655-60.
Carreira M, Estrada M. Mama densa, ¿qué debemos saber? Implicaciones en el cribado. Radiología. 2016;58(6):421-6.
Zuppan P, Hall JM, Lee MK, Ponglikitmongkol M, King MC. Possible linkage of the estrogen receptor gene to breast cancer in a family with late-onset disease. Am J Hum Genet. 1991;48(6):1065-8.
Gonzalez-Mancha R, Galan JJ, Crespo C, Iglesias-Perez L, Gonzalez-Perez A, Moron FJ, et al. Analysis of the ERalpha germline PvuII marker in breast cancer risk. Med Sci Monit. 2008;14:CR136-43.
Parl F, Cavener D, Dupont W. Genomic DNA analysis of the estrogen receptor gene in breast cancer. Breast Cancer Res Treat. 1989;14(1):57-64.
Hill SM, Fuqua SA, Chamness GC, Greene GL, McGuire WL. Estrogen receptor expression in human breast cancer associated with an estrogen receptor gene restriction fragment length polymorphism. Cancer Res. 1989;49:145-8.
Herrington D, Howard T, Brosnihan K, McDonnell D, Li X, Hawkins G, et al. Common estrogen receptor polymorphism augments effects of hormone replacement therapy on E-selectin but not C-Reactive Protein. Circulation. 2002;105(16):1879-82.
Schuit S. Estrogen receptor α gene polymorphisms and risk of myocardial infarction. JAMA. 2004;291(24):2969.
Maruyama H, Toji H, Harrington C, Sasaki K, Izumi Y, Ohnuma T, et al. Lack of an association of estrogen receptor α gene polymorphisms and transcriptional activity with Alzheimer disease. Arch Neurology. 2000;57(2):236.
Greendale G, Palla S, Ursin G, Laughlin G, Crandall C, Pike M, et al. The association of endogenous sex steroids and sex steroid binding proteins with mammographic density: Results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study. Am J Epidemiol. 2005;162(9):826-34.
Gram I, Bremnes Y, Ursin G, Maskarinec G, Bjurstam N, Lund E. Percentage density, Wolfe’s and Tabár’s mammographic patterns: agreement and association with risk factors for breast cancer. Breast Cancer Res. 2005;7(5) R854-61.