Interaction of environmental and genetic factors associated with the development of ovarian cancer
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Abstract
Ovarian cancer is the deadlist gynecological neoplasia due to its asymptomatology and its advanced stage of diagnosis. The incidence rate worldwide is at 6.3 for each 100,000 women, where the highest rates are found in the industrialized geographic areas, such as Europe (10.1), North America (8.7) and Oceania (7.6). Some of the risk factors that are mostly associated with the development of this type of cancer are: advanced age, uncontrolled levels of hormone loading, obesity, family history of cancer, exposure to carcinogenic agents, presence of pathogenic agents and genetic mutations. Regarding genetic profiling, the presence of mutations in different molecular biomarkers (tumor supressors, oncogenes, apoptotic genes and DNA repairs) increases the risk to develop ovarian cancer. Among the most representative genes are: BRCA1, BRCA2, TP53, RAD51 and VDR. On the other hand, the correct treatment carried out for this disease will depend on the tumor stage age, capacity to absorb medicine, histopathology, hormonal loading and genetic profiling. The most common treatments are: surgery, homeopathic medicaments, drugs, micro RNA’s and multikinase inhibitors application. In conclusion, the development of cancer (ovarian) will depend on four relevant variables: (1) time and (2) exposure dose to carcinogens, (3) advanced age, and (4) genetic predisposition. In other words, the association between the environmental factors and the genetic factors triggers the development of cancer
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Benítez Capistros F, Benítez Capistros R, Echeverría C, Oña Cisneros F, Paz y Miño C, López Cortés A. Interaction of environmental and genetic factors associated with the development of ovarian cancer. REMCB [Internet]. 2017Aug.14 [cited 2024Jul.3];35(1-2):9-20. Available from: https://remcb-puce.edu.ec/remcb/article/view/246
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Artículos Científicos
References
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Bankhead C, Collins C, Stokes-Lampard H, Rose P, Wilson S, Clements A, Mant D, Kehoe S, Austoken J. 2008. Identifying symptoms of ovarian cancer: a qualitative and quantitative study. BJOG: An Interna-tional Journal of Obstetrics and Gynaecology, 115(8): 1008–14.
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Bernstein L. 2006. The risk of breast, endometrial and ovarian cancer in users of hormonal preparations. Basic y Clinical Pharmacology y Toxicology, 98: 288–96.
Bradlow H, Sepkovic D, Telang N, Osborne M. 1999. Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Annals of the New York Academy of Sciences, 889:204–13.
Cabrera-Andrade A, López-Cortés A, Muñoz M. J, Jaramillo-Koupermann G, Rodríguez O, Leone P. E, Paz-y-Miño C. 2014. Asso-ciation of genetic variants of membrane receptors related to recognition and induction of immune response with Heli-cobacter pylori infection in Ecuadorian individuals. International Journal of Immu-nogenetics, DOI: 10.1111/iji.12118.
Chang E, Lee V, Canchola A, Clarke C, Purdie D, Reynolds P, Anton-Culver H, Bernstein L, Deapen D, Peel D, Pinder R, Ross R, Stram D, West D, Wright W, Ziogas A, Horn-Ross P. 2007. Diet and risk of ovarian cancer in the California Teachers Study cohort. American Journal of Epidemiology, 165(7):802–13.
Chen H, Hardy T y Tollefsbol T. 2011. Epigenomics of ovarian cancer and its chemopreven-tion. Frontiers in Genetics, 2:67.
Chen X y Anderson J. 2001. Isoflavones inhibit proliferation of ovarian cancer cells in vitro via an estrogen receptor-dependent pathway. Nutrition and cancer, 41:165–71
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Chuaire-Noack L, Sánchez-Corredor M, Ramírez-Clavijo S. 2008. P53 and its role in the ovarían surface epithelium. A review. Investigación Clínica, 49(4): 561–93.
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Cornwell T, Cohick W, Raskin I. 2004. Dietary phytoestrogens and health. Phytochemis-try, 65: 995–1016.
Cueva P y Yépez J. 2009. Epidemiología del cánc-er en Quito 2003-2005. Registro Nacional de Tumores (RNT). SOLCA. Quito, Ecua-dor. 200 pp.
Dahiya N y Morin P. 2010. MicroRNAs in ovarian carcinomas. Endocrine-Related Cancer, 17(1): 77–89.
Duarte F, Camesselle-Teijeiro J, Soares R, Seixas C, Cortizo-Torres M. 2002. Análisis de muta-ciones en los genes BRCA1 y BRCA2 en pacientes con cáncer de mama y ovario del norte de Portugal y Galicia. Revista Clínica Española, 202(5): 259–63.
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Harlow B, Cramer D, Bell D, Welch W. 1992. Perineal exposure to talc and ovarian cancer risk. Obstetrics and Gynecology, 80(1): 19–26.
Harrison M., Jameson C., Gore M. 2008. Muci-nous ovarian cancer. International Journal of Gynecological Cancer, 18(2): 209–14.
Hernández M y Ríos M. 1999. Oncogenes y Cáncer. Revista Cubana de Oncología, 15(2): 131–9.
Irigaray P, Newby J, Clapp R, Hardell L, Howard V, Montagnier L, Epstein S y Bel-pomme D. 2007. Lifestyle-related factors and environmental agents causing cancer: an overview. Biomedicine y Pharmaco-therapy, 61(10): 640–58.
Karst A y Drapkin R. 2010. Ovarian cancer patho-genesis: a model in evolution. Journal of Oncology, 1–13.
Kuiper G, Lemmen J, Carlsson B, Corton J, Safe S, van der Saag P, van der Burg y Gustafsson J. 1998. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology, 139(10): 4252–63.
Kurman R y Shih I. 2008. Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. International Journal of Gynecological Pathology, 27(2): 151–60.
Kwon M y Shin Y. 2011. Epigenetic regulation of cancer-associated genes in ovarian cancer. International Journal of Molecular Sciences, 12(2): 983–1008.
Lagos E y Soto T. 2007. Epigenética y cáncer. Revista Médica de Costa Rica y Centroamerica, 580: 177–182.
Lampe J y Peterson S. 2002. Brassica, biotrans-formation and cancer risk: genetic poly-morphisms alter the preventive effects of cruciferous vegetables. The Journal of Nutrition, 132(10): 2991–4.
Lee K y Young R. 2003. The distinction between primary and metastatic mucinous carci-nomas of the ovary: gross and histologic findings in 50 cases. The American Journal of Surgical Pathology. 27(3): 281–92.
Lengyel E. 2010. Ovarian cancer development and metastasis. The American Journal of Pathology, 177(3): 1053–64.
Mills P, Riordan D, Cress R y Young H. 2004. Perineal talc exposure and epithelial ovarian cancer risk in the Central Valley of California. International Journal of Cancer, 112(3): 458–64.
Modugno F, Ness R y Cottreau C. 2002. Cigarette smoking and the risk of mucinous and nonmucinous epithelial ovarian cancer. Epidemiology, 13:467–71.
Mohapatra S, Saxena A, Gandhi G, Koner B y Ray P. 2013. Vitamin D and VDR gene polymorphism (FokI) in epithelial ovarian cancer in Indian population. Journal of Ovarian Research, 6(1): 37.
Moore K. 2010. Clinically Oriented Anatomy. Sixth Edition. Lippincott Williams and Wilkins. USA.
Moorman P, Claingaert B, Palmieri R, Iversen E, Bentley R, Halabi S, Berchuck A y Schil-dkraut J. 2008. Hormonal risk factors for ovarian cancer in premenopausal and postmenopausal women. American Journal of Epidemiology, 167(9): 1059–69.
Muñoz MJ, López-Cortés A, Sarmiento I, Herrera C, Sánchez ME y Paz-y-Miño C. 2008. Bio-monitoreo genetico de individuos expuestos a radiación ionizante y su relación con el desarrollo de cancer. Oncología, 18(1-4): 75–82.
Nagle C, Olsen C, Webb P, Jordan S, Whiteman D, Green A, Australian Cancer Study Group y Australian Ovarian Cancer Study Group. 2008. Endometrioid and clear cell ovarian cancers: a comparative analysis of risk factors. European Journal of Cancer, 44(16): 2477–84.
National Cancer Institute. 2013. Cáncer epitelial de ovarios: Tratamiento. National Institute of Health. Página de Internet: http://www. cancer.gov/espanol/pdq/tratamiento/ epitelial-de-ovarios/HealthProfessional/ page5 Consultada 5-noviembre-2013.
Nicolopoulou-Stamati P, Hens L, Howard V y van Larebeke N. 2004. Cancer as an Envi-ronmental Disease. Environmental Science and Technology Library. Kluwer Academic Publishers. Holanda.
Organización Mundial de la Salud (OMS). 2009. Cancer: Fact sheet 292. Página de Internet: http://www.who.int/mediacen-tre/factsheets/fs297/en/ Consultada 30-mayo-2011.
Pasalich M, Su D, Binns C y Lee A. 2013. Reproductive factors for ovarian cancer in southern Chinese women. Journal of Gynecologic Oncology, 24(2): 135–40.
Patel A, Galaal K, Burnley C, Faulkner K, Mar-tin-Hirsch P, Bland M, Leeson S, Beer H, Paranjothy S, Sasieni P y Naik R. 2012. Cer-vical cancer incidence in young women: a historical and geographical controlled UK regional population study. British Journal of Cancer, 106(11): 1753–9.
Paz-y-Miño C, López-Cortés A, Muñoz MJ, Cabrera A, Castro Bernardo, Sánchez M E. 2010. Incidence of the L858R and G719S mutations of the epidermal growth factor receptor oncogene in an Ecuadorian popu-lation with lung cancer. Cancer Genetics and Cytogenetics, 196: 201–3.
Paz-y-Miño C, López-Cortés A, Arévalo M, Sánchez ME. 2008. Monitoring of DNA damage in exposed individuals to petro-leum hydrocarbons in Ecuador. Annals of the New York Academy of Sciences, 1140: 121–8.
Pearce C, Templeman C, Rossing M, Lee A, Near A, Webb P, Nagle C, Doherty J, Cushing-Hau-gen K, Wicklund K., et al. 2012. Associa-tion between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. The Lancet Oncology, 13(4): 385–94.
Pelissero C, Lenczowski MJ, Chinzi D, Davail-Cuisset B, Sumpter J, Fostier A. 1996. Effects of flavonoids on aromatase activity, an in vitro study. The Journal of Steroid Biochemistry and Molecular Biology, 57(3-4): 215–23.
Sánchez P y Gómez A. 2005. Cáncer de Ovario. Medicine, 1667–74.
Shulman L y Dungan J. 2010. Cancer genetics: risks and mechanisms of cancer in women with inherited susceptibility to epithelial ovarian cancer. Cancer Treatment and Research, 156: 69–85.
Singletary S, Allred C, Ashley P, Bassett L, Berry D, Borgen P, Clark G, Edge S, Hayes D, Hughes L, Hutter R, Morrow M, Page D, Recht A, Theriault R, Thor A, Weaver D, Wlieand H y Greene F. 2002. Revision of the American Joint Committee on Cancer staging system for breast cancer. Journal of Clinical Oncology, 20(17): 3628–36.
Smolle E, Taucher V, Pichler M, Petru E, Lax S, Haybaeck J. 2013. Targeting signaling pathways in epithelial ovarian cancer. International Journal of Molecular Sciences, 14(5): 9536–55.
Takai N, Kira N, Ishii T, Yoshida T, Nishida Y, Nasu K y Narahara H. 2012. Bufalin, a traditional oriental medicine, induces apoptosis in human cancer cells. Asian Pacific Journal of Cancer Prevention, 13(1): 399–402.
Tworoger S, Lee I, Buring J, Rosner B, Hollis B y Hankinson S. 2007. Plasma 25-hydroxyvi-tamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiological, Biomarkers & Prevention, 16(4): 783–8.
Vademecum. 2011. Vademecum International 2011. Editorial Medicom. Barcelona, España.
Wilhelm S, Adnane L, Newell Ph, Villanueva A, Llovet J, Lynch M. 2008. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase sig-naling. Molecular Cancer Therapeutics, 7: 3129–40.
Woodward W, Strom E, Tucker S, McNeese M, Perkins G, Schechter N, Singletary S, Theriault R, Hortobagyi G, Hunt K, Buchholz T. 2003. Changes in the 2003 American Joint Committee on Cancer staging for breast cancer dramatically affect stage-specific survival. Journal of Clinical Oncology, 21(17): 3244–8.
Wrzeszczynski K, Varadan V, Byrnes J, Lum E, Kamalakaran S, Levine A, Dimitrova N, Zhang M y Lucito R. 2011. Identifica-tion of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancer. PLOS One, 6(12): e28503.
Al Rawahi T, Lopes A, Bristow R, Brayant A, Elattar A, Chattopadhyay S, Galaal K. 2013. Surgical cytoreduction for recurrent epithelial ovarian cancer. John Wiley & Sons Ltd. USA. 45 pp.
American Cancer Society. 2013. Ovarian Cancer. Página de Internet: http://www.cancer. org/cancer/ovariancancer/detailedguide/ index Consultada 10-diciembre-2013.
Auborn K, Fan S, Rosen E, Goodwin L, Chan-draskaren A., William D., Chen D. y Carter T. 2003. Indole-3-carbinol is a negative regulator of estrogen. The Journal of Nutri-tion, 133(7 Suppl): 2470S–5S.
Baba A y Cătoi C. 2007. Comparative Oncology. The Publishing House of the Romanian Academy. Bucharest, Romania.
Bankhead C, Collins C, Stokes-Lampard H, Rose P, Wilson S, Clements A, Mant D, Kehoe S, Austoken J. 2008. Identifying symptoms of ovarian cancer: a qualitative and quantitative study. BJOG: An Interna-tional Journal of Obstetrics and Gynaecology, 115(8): 1008–14.
Bast R, Hennessy B y Mills G. 2009. The biology of ovarian cancer: new opportunities for translation. Nature Reviews Cancer, 9(6): 415–28.
Bernstein L. 2006. The risk of breast, endometrial and ovarian cancer in users of hormonal preparations. Basic y Clinical Pharmacology y Toxicology, 98: 288–96.
Bradlow H, Sepkovic D, Telang N, Osborne M. 1999. Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Annals of the New York Academy of Sciences, 889:204–13.
Cabrera-Andrade A, López-Cortés A, Muñoz M. J, Jaramillo-Koupermann G, Rodríguez O, Leone P. E, Paz-y-Miño C. 2014. Asso-ciation of genetic variants of membrane receptors related to recognition and induction of immune response with Heli-cobacter pylori infection in Ecuadorian individuals. International Journal of Immu-nogenetics, DOI: 10.1111/iji.12118.
Chang E, Lee V, Canchola A, Clarke C, Purdie D, Reynolds P, Anton-Culver H, Bernstein L, Deapen D, Peel D, Pinder R, Ross R, Stram D, West D, Wright W, Ziogas A, Horn-Ross P. 2007. Diet and risk of ovarian cancer in the California Teachers Study cohort. American Journal of Epidemiology, 165(7):802–13.
Chen H, Hardy T y Tollefsbol T. 2011. Epigenomics of ovarian cancer and its chemopreven-tion. Frontiers in Genetics, 2:67.
Chen X y Anderson J. 2001. Isoflavones inhibit proliferation of ovarian cancer cells in vitro via an estrogen receptor-dependent pathway. Nutrition and cancer, 41:165–71
Chobanian N y Dietrich Ch. 2008. Cáncer de ovario. Surgical Clinics of North America, 45:149–166.
Chuaire-Noack L, Sánchez-Corredor M, Ramírez-Clavijo S. 2008. P53 and its role in the ovarían surface epithelium. A review. Investigación Clínica, 49(4): 561–93.
Clavel J. 2007. Progress in the epidemiologi-cal understanding of gene-environment interactions in major diseases: cancer. Comptes Rendus Biologies, 330(4): 306–17.
Cornwell T, Cohick W, Raskin I. 2004. Dietary phytoestrogens and health. Phytochemis-try, 65: 995–1016.
Cueva P y Yépez J. 2009. Epidemiología del cánc-er en Quito 2003-2005. Registro Nacional de Tumores (RNT). SOLCA. Quito, Ecua-dor. 200 pp.
Dahiya N y Morin P. 2010. MicroRNAs in ovarian carcinomas. Endocrine-Related Cancer, 17(1): 77–89.
Duarte F, Camesselle-Teijeiro J, Soares R, Seixas C, Cortizo-Torres M. 2002. Análisis de muta-ciones en los genes BRCA1 y BRCA2 en pacientes con cáncer de mama y ovario del norte de Portugal y Galicia. Revista Clínica Española, 202(5): 259–63.
Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D. 2010. Estimates of world-wide burden of cancer in 2010: GLOBO-CAN 2008. International Journal of Cancer, 127(12): 2893–917.
Frank S A. 2007. Dynamics of cancer incidence, inheritance, and evolution. Princeton University Press. Princeton and Oxford. United Kingdom. 273 pp.
Grant W. 2006. Lower vitamin-D production from solar ultraviolet-B irradiance may explain some differences in cancer survival rates. Journal of the National Medical Association, 3(6): 357–64.
Harlow B, Cramer D, Bell D, Welch W. 1992. Perineal exposure to talc and ovarian cancer risk. Obstetrics and Gynecology, 80(1): 19–26.
Harrison M., Jameson C., Gore M. 2008. Muci-nous ovarian cancer. International Journal of Gynecological Cancer, 18(2): 209–14.
Hernández M y Ríos M. 1999. Oncogenes y Cáncer. Revista Cubana de Oncología, 15(2): 131–9.
Irigaray P, Newby J, Clapp R, Hardell L, Howard V, Montagnier L, Epstein S y Bel-pomme D. 2007. Lifestyle-related factors and environmental agents causing cancer: an overview. Biomedicine y Pharmaco-therapy, 61(10): 640–58.
Karst A y Drapkin R. 2010. Ovarian cancer patho-genesis: a model in evolution. Journal of Oncology, 1–13.
Kuiper G, Lemmen J, Carlsson B, Corton J, Safe S, van der Saag P, van der Burg y Gustafsson J. 1998. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology, 139(10): 4252–63.
Kurman R y Shih I. 2008. Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. International Journal of Gynecological Pathology, 27(2): 151–60.
Kwon M y Shin Y. 2011. Epigenetic regulation of cancer-associated genes in ovarian cancer. International Journal of Molecular Sciences, 12(2): 983–1008.
Lagos E y Soto T. 2007. Epigenética y cáncer. Revista Médica de Costa Rica y Centroamerica, 580: 177–182.
Lampe J y Peterson S. 2002. Brassica, biotrans-formation and cancer risk: genetic poly-morphisms alter the preventive effects of cruciferous vegetables. The Journal of Nutrition, 132(10): 2991–4.
Lee K y Young R. 2003. The distinction between primary and metastatic mucinous carci-nomas of the ovary: gross and histologic findings in 50 cases. The American Journal of Surgical Pathology. 27(3): 281–92.
Lengyel E. 2010. Ovarian cancer development and metastasis. The American Journal of Pathology, 177(3): 1053–64.
Mills P, Riordan D, Cress R y Young H. 2004. Perineal talc exposure and epithelial ovarian cancer risk in the Central Valley of California. International Journal of Cancer, 112(3): 458–64.
Modugno F, Ness R y Cottreau C. 2002. Cigarette smoking and the risk of mucinous and nonmucinous epithelial ovarian cancer. Epidemiology, 13:467–71.
Mohapatra S, Saxena A, Gandhi G, Koner B y Ray P. 2013. Vitamin D and VDR gene polymorphism (FokI) in epithelial ovarian cancer in Indian population. Journal of Ovarian Research, 6(1): 37.
Moore K. 2010. Clinically Oriented Anatomy. Sixth Edition. Lippincott Williams and Wilkins. USA.
Moorman P, Claingaert B, Palmieri R, Iversen E, Bentley R, Halabi S, Berchuck A y Schil-dkraut J. 2008. Hormonal risk factors for ovarian cancer in premenopausal and postmenopausal women. American Journal of Epidemiology, 167(9): 1059–69.
Muñoz MJ, López-Cortés A, Sarmiento I, Herrera C, Sánchez ME y Paz-y-Miño C. 2008. Bio-monitoreo genetico de individuos expuestos a radiación ionizante y su relación con el desarrollo de cancer. Oncología, 18(1-4): 75–82.
Nagle C, Olsen C, Webb P, Jordan S, Whiteman D, Green A, Australian Cancer Study Group y Australian Ovarian Cancer Study Group. 2008. Endometrioid and clear cell ovarian cancers: a comparative analysis of risk factors. European Journal of Cancer, 44(16): 2477–84.
National Cancer Institute. 2013. Cáncer epitelial de ovarios: Tratamiento. National Institute of Health. Página de Internet: http://www. cancer.gov/espanol/pdq/tratamiento/ epitelial-de-ovarios/HealthProfessional/ page5 Consultada 5-noviembre-2013.
Nicolopoulou-Stamati P, Hens L, Howard V y van Larebeke N. 2004. Cancer as an Envi-ronmental Disease. Environmental Science and Technology Library. Kluwer Academic Publishers. Holanda.
Organización Mundial de la Salud (OMS). 2009. Cancer: Fact sheet 292. Página de Internet: http://www.who.int/mediacen-tre/factsheets/fs297/en/ Consultada 30-mayo-2011.
Pasalich M, Su D, Binns C y Lee A. 2013. Reproductive factors for ovarian cancer in southern Chinese women. Journal of Gynecologic Oncology, 24(2): 135–40.
Patel A, Galaal K, Burnley C, Faulkner K, Mar-tin-Hirsch P, Bland M, Leeson S, Beer H, Paranjothy S, Sasieni P y Naik R. 2012. Cer-vical cancer incidence in young women: a historical and geographical controlled UK regional population study. British Journal of Cancer, 106(11): 1753–9.
Paz-y-Miño C, López-Cortés A, Muñoz MJ, Cabrera A, Castro Bernardo, Sánchez M E. 2010. Incidence of the L858R and G719S mutations of the epidermal growth factor receptor oncogene in an Ecuadorian popu-lation with lung cancer. Cancer Genetics and Cytogenetics, 196: 201–3.
Paz-y-Miño C, López-Cortés A, Arévalo M, Sánchez ME. 2008. Monitoring of DNA damage in exposed individuals to petro-leum hydrocarbons in Ecuador. Annals of the New York Academy of Sciences, 1140: 121–8.
Pearce C, Templeman C, Rossing M, Lee A, Near A, Webb P, Nagle C, Doherty J, Cushing-Hau-gen K, Wicklund K., et al. 2012. Associa-tion between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. The Lancet Oncology, 13(4): 385–94.
Pelissero C, Lenczowski MJ, Chinzi D, Davail-Cuisset B, Sumpter J, Fostier A. 1996. Effects of flavonoids on aromatase activity, an in vitro study. The Journal of Steroid Biochemistry and Molecular Biology, 57(3-4): 215–23.
Sánchez P y Gómez A. 2005. Cáncer de Ovario. Medicine, 1667–74.
Shulman L y Dungan J. 2010. Cancer genetics: risks and mechanisms of cancer in women with inherited susceptibility to epithelial ovarian cancer. Cancer Treatment and Research, 156: 69–85.
Singletary S, Allred C, Ashley P, Bassett L, Berry D, Borgen P, Clark G, Edge S, Hayes D, Hughes L, Hutter R, Morrow M, Page D, Recht A, Theriault R, Thor A, Weaver D, Wlieand H y Greene F. 2002. Revision of the American Joint Committee on Cancer staging system for breast cancer. Journal of Clinical Oncology, 20(17): 3628–36.
Smolle E, Taucher V, Pichler M, Petru E, Lax S, Haybaeck J. 2013. Targeting signaling pathways in epithelial ovarian cancer. International Journal of Molecular Sciences, 14(5): 9536–55.
Takai N, Kira N, Ishii T, Yoshida T, Nishida Y, Nasu K y Narahara H. 2012. Bufalin, a traditional oriental medicine, induces apoptosis in human cancer cells. Asian Pacific Journal of Cancer Prevention, 13(1): 399–402.
Tworoger S, Lee I, Buring J, Rosner B, Hollis B y Hankinson S. 2007. Plasma 25-hydroxyvi-tamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiological, Biomarkers & Prevention, 16(4): 783–8.
Vademecum. 2011. Vademecum International 2011. Editorial Medicom. Barcelona, España.
Wilhelm S, Adnane L, Newell Ph, Villanueva A, Llovet J, Lynch M. 2008. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase sig-naling. Molecular Cancer Therapeutics, 7: 3129–40.
Woodward W, Strom E, Tucker S, McNeese M, Perkins G, Schechter N, Singletary S, Theriault R, Hortobagyi G, Hunt K, Buchholz T. 2003. Changes in the 2003 American Joint Committee on Cancer staging for breast cancer dramatically affect stage-specific survival. Journal of Clinical Oncology, 21(17): 3244–8.
Wrzeszczynski K, Varadan V, Byrnes J, Lum E, Kamalakaran S, Levine A, Dimitrova N, Zhang M y Lucito R. 2011. Identifica-tion of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancer. PLOS One, 6(12): e28503.