Chemoprevention of Ovarian Cancer

  • Anna HoekstraEmail author
  • Gustavo C. Rodriguez
Part of the Cancer Treatment and Research book series (CTAR, volume 149)


Epithelial ovarian cancer remains a highly lethal malignancy. It is the fourth to fifth leading cause of cancer deaths among women in the United States and causes more than 140,000 deaths annually in women worldwide.1 Despite intensive research efforts over the past decade directed toward improved detection and treatment of ovarian cancer, the long-term survival of women with ovarian cancer has only improved modestly. Progress in the fight against ovarian cancer has been hampered by a number of factors, including late diagnosis, the absence of highly curative chemotherapy, and a high degree of molecular heterogeneity in ovarian tumors, a finding that is a direct consequence of the large tumor burden typical in most patients at the time of presentation.

The unusually large tumor burden that characterizes most advanced ovarian cancers at diagnosis makes ovarian cancer uniquely different than other solid tumors. Most women (75%) diagnosed with ovarian cancer have disseminated...


  1. 1.
    Jemal A, Siegel R, Ward E, et al. Cancer Statistics. CA Cancer J Clin. 2008;58:71–96.PubMedCrossRefGoogle Scholar
  2. 2.
    Goldie J, Coldman A. A mathematical model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep. 1979;63:1727–1733.PubMedGoogle Scholar
  3. 3.
    Hoskins W. Prospective on ovarian cancer: why prevent? J Cell Biochem. 1995;23:189–199.CrossRefGoogle Scholar
  4. 4.
    Fathalla MF. Incessant ovulation: a factor in ovarian neoplasia? Lancet. 1971;2:163.PubMedCrossRefGoogle Scholar
  5. 5.
    Whittemore AS, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk: collarborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Am J Epidemiol. 1992;136:1184–1203.PubMedGoogle Scholar
  6. 6.
    Risch HA, Marrett LD, Howe GR. Parity, contraception, infertility, and the risk of epithelial ovarian cancer. Am J Epidemiol. 1994;140:585–597.PubMedGoogle Scholar
  7. 7.
    Riman T, Dickman PW, Nilsson S, Nordlinder H, Magnusson C, Persson I. Risk factors for invasive epithelial ovarian cancer: results from a Swedish case-control study. Am J Epidemiol. 2002;156:363–373.PubMedCrossRefGoogle Scholar
  8. 8.
    Gwinn M, Lee N, Rhodes P, Layde P, Rubin G. Pregnancy, breast feeding, and oral contraceptives and the risk of epithelial ovarian cancer. J Clin Epidemiol. 1990;43:559–568.PubMedCrossRefGoogle Scholar
  9. 9.
    Nasca P, Greenwald P, Chorost S, Richart R, Caputo T. An epidemiologic case-control study of ovarian cancer and reproductive factors. Am J Epidemiol. 1984;119:705–713.PubMedGoogle Scholar
  10. 10.
    Fredrickson T. Ovarian tumors of the hen. Environ Health Perspect. 1987;73:35–51.PubMedCrossRefGoogle Scholar
  11. 11.
    Tsao AS, Kim ES, Hong WK. Chemoprevention of cancer. CA Cancer J Clin. 2004;54:150–180.PubMedCrossRefGoogle Scholar
  12. 12.
    Baer-Dubowska. Cancer chemopreventitive agents—drugs for the 21st century? Acta Pol Pharm. 2006;63(5):369–373.PubMedGoogle Scholar
  13. 13.
    Sporn MB. Approaches to prevention of epithelial cancer during the preneoplastic period. Cancer Res. 1976;36:2699–2702.PubMedGoogle Scholar
  14. 14.
    Anonymous. Prevention of cancer in the next millennium: report of the chemoprevention working group to the American Association for Cancer Research. Cancer Res. 1999;59:4743–4758.Google Scholar
  15. 15.
    The Alpha Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994;330:1029–1035.Google Scholar
  16. 16.
    BJelakovic G, Nikolava D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis JAMA. 2007;297:842–857.PubMedCrossRefGoogle Scholar
  17. 17.
    Leary J, Edwards B, Houghton C, Kefford R, Friedlander M. Amplification of HER-2/neu oncogene in human ovarian cancer. Int J Gyncol Cancer. 1992;2:291–94.CrossRefGoogle Scholar
  18. 18.
    Bartlett J, Langdon S, Simpson B, et al. The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer. Br J Cancer. 1996;73:301–306.PubMedGoogle Scholar
  19. 19.
    Sporn M, Liby K. Cancer chemoprevention: scientific promise, clinical uncertainty. Nat Clin Pract Oncol. 2005;2(10):518–525.PubMedCrossRefGoogle Scholar
  20. 20.
    Finkler NJ, Gordon A, Crozier M. Phase 2 evaluation of OSI-774, a potent oral antagonist of the EGFR-TK in patients with advanced ovarian cancer. Program and abstracts of the 37th Annual Meeting of the American Society of Clinical Oncology; May 12–15, 2001; San Francisco, CA. Abstract 831.Google Scholar
  21. 21.
    Dudek H, Datta S, Franke T, et al. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science. 1997;275:661–665.PubMedCrossRefGoogle Scholar
  22. 22.
    Di Cristofano A, Pandolfi P. The multiple roles of PTEN in tumor suppression. Cell. 2000;100:387–390.PubMedCrossRefGoogle Scholar
  23. 23.
    Tsao A, McDonnell T, Lam S, et al. Increased phospho-AKT (Ser(473)) expression in bronchial dysplasia: implications for lung cancer prevention studies. Cancer Epidemiol Biomarkers Prev. 2003;12:660–664.PubMedGoogle Scholar
  24. 24.
    Ward EC, Hoekstra AV, Blok LJ, et al. The regulation and function of the forkhead transcription factor, Forkhead box O1, is dependent on the progesterone receptor in endometrial carcinoma. Endocrinology. 2008;149:1942–1950.PubMedCrossRefGoogle Scholar
  25. 25.
    Hill M, Hemmings B. Inhibition of protein kinase B/Akt: implications for cancer therapy. Pharmacol Ther. 2002;93:243–251.PubMedCrossRefGoogle Scholar
  26. 26.
    Cheng J, Godwin A, Bellacosa A, et al. AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc Natl Acad Sci USA. 1992;89:9267–9271.PubMedCrossRefGoogle Scholar
  27. 27.
    Aggarwal B, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharma. 2006;71:1397–1421.CrossRefGoogle Scholar
  28. 28.
    Schildkraut JM, Bastos E, Berchuck A. Relationship between lifetime ovulatory cycles and overexpression of mutant p53 in epithelial ovarian cancer. J Natl Cancer Inst. 1997;89(13):932–938.PubMedCrossRefGoogle Scholar
  29. 29.
    Michalovitz D, Halevy O, Oren M. p53 gene mutations: gains or losses? J Cell Biochem. 1991;45:22–29.PubMedCrossRefGoogle Scholar
  30. 30.
    Marks J, Davidoff A, Kerns B, et al. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res. 1991;51:2979–2984.PubMedGoogle Scholar
  31. 31.
    Landen C, Birrer M, Sood A. Early events in the pathogenesis of epithelial ovarian cancer. J Clin Oncol. 2008;26:995–1005.PubMedCrossRefGoogle Scholar
  32. 32.
    Kohler M, Marks J, Wiseman R. Spectrum of mutation and frequency of allelic deletion of the p53 gene in ovarian cancer. J Natl Cancer Inst. 1993;85:1513–1519.PubMedCrossRefGoogle Scholar
  33. 33.
    Kupryjanczyk J, Thor A, Beauchamp R, et al. p53 gene mutations and protein accumulation in human ovarian cancer. Proc Natl Acad Sci USA. 1993;90:4961–4965.PubMedCrossRefGoogle Scholar
  34. 34.
    Skilling J, Sood A, Niemann T, Lager D, Buller R. An abundance of p53 null mutations in ovarian carcinoma. Oncogene. 1996;13:117–123.PubMedGoogle Scholar
  35. 35.
    Aggarwal BB. Nuclear factor-kappaB: the enemy within. Cancer Cell. 2004;6(3):203–208.PubMedCrossRefGoogle Scholar
  36. 36.
    Deregowski V, Delhalle S, Benoit V, Bours V, Merville MP. Identification of cytokine-induced nuclear factor-kappaB target genes in ovarian and breast cancer cells. Biochem Pharmacol. 2002;64:873–881.PubMedCrossRefGoogle Scholar
  37. 37.
    Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem. 1995;270(42):24995–25000.PubMedCrossRefGoogle Scholar
  38. 38.
    Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol. 2000;164(12):6509–6519.PubMedGoogle Scholar
  39. 39.
    Yang F, Oz HS, Bve S, de Villiers WJ, McClain CJ, Varilek GW. The green tea polyphenol (-)-epigallocatechin-3-gallate blocks nuclear factor-kappa B activation by inhibiting I kappa B kinase activity in the intestinal epithelial cell line IEC-6. Mol Pharmacol. 2001;60(3):528–533.PubMedGoogle Scholar
  40. 40.
    Huang S, Robinson J, Deguzman A, Bucana C, Fidler I. Blockade of nuclear factor-kappaB signaling inhibits angiogenesis and tumorigenicity of human ovarian cancer cells by suppressing expression of vascular endothelial growth factor and interleukin B. Cancer Res. 2000;60:5334–5339.PubMedGoogle Scholar
  41. 41.
    Matthews C, Colburn N, Young M. AP-1 a target for cancer prevention. Curr Cancer Drug Tar. 2007;7:317–324.CrossRefGoogle Scholar
  42. 42.
    Young M, Yang H, Colburn N. Promising molecular targets for cancer prevention: AP-1, NF-kappa B and Pdcd4. Trends Mol Med. 2003;9:36–41.PubMedCrossRefGoogle Scholar
  43. 43.
    Canman CE, Chen C-Y, Lee MH, Castan MB. DNA damage responses: p53 induction, cell cycle pertubations, and apoptosis. Cold Spring Harbor Symposia on Quantitative Biology, LIX. Woodbury NY: Cold Spring Harbor Press; 1994:277–286.Google Scholar
  44. 44.
    Ponzoni M, Bocca P, Chiesa V, et al. Differential effects of N-(4-hydroxyphenyl) retinamide and retinoic acid on neuroblastoma cells: apoptosis versus differentiation. Cancer Res. 1995;55(4):853–861.PubMedGoogle Scholar
  45. 45.
    Delia D, Aiello A, Lombardi L, et al. N-(4-hydroxyphenyl) retinamide induces apoptosis of malignant hemopoietic cell lines including those unresponsive to retinoic acid. Cancer Res. 1993;53(24):6036–6041.PubMedGoogle Scholar
  46. 46.
    Lotan R. Retinoids in cancer chemoprevention. FASEB J. 1996;10(9):1031–1039.PubMedGoogle Scholar
  47. 47.
    Kuo SM. Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells. Cancer Lett. 1996;110(1–2):41–48.PubMedCrossRefGoogle Scholar
  48. 48.
    Thompson HJ, Jiang C, Lu J, et al. Sulfone metabolite of sulindac inhibits mammary carcinogenesis. Cancer Res. 1997;57(3):420–425.Google Scholar
  49. 49.
    Gould MN. Cancer chemoprevention and therapy by monoterpenes. Environ Health Perspect. 1997;105(Suppl 4):977–979.PubMedCrossRefGoogle Scholar
  50. 50.
    Pascale RM, Simile MM, De Miglio MR, et al. Chemoprevention by S-adenosyl-L-methionine of rat liver carcinogenesis initiated by 1,2-dimethylhydrazine and promoted by orotic acid. Carcinogenesis. 1995;16(2):427–430.PubMedCrossRefGoogle Scholar
  51. 51.
    el-Bayoumy K, Upadhyaya P, Chae YH, et al. Chemoprevention of cancer by organoselenium compounds. J Cell Biochem Suppl. 1995;22:92–100.PubMedCrossRefGoogle Scholar
  52. 52.
    Sun SY, Hail N, Lotan R. Apoptosis as a novel target for cancer prevention. J Natl Cancer Inst. 2004;96:662–672.PubMedCrossRefGoogle Scholar
  53. 53.
    Ouyang N, Williams JL, Rigas B. NO-donating aspirin isomers downregulate peroxisome proliferator-activated receptor (PPAR)delta expression in APC(min/+) mice proportionally to their tumor inhibitory effect: implications for the role of PPARdelta in carcinogenesis. Carcinogenesis. 2006;27(2):232–239.PubMedCrossRefGoogle Scholar
  54. 54.
    Sinicrope FA, Half E, Morris JS, et al. Cell proliferation and apoptotic indices predict adenoma regression in a placebo-controlled trial of celecoxib in familial adenomatous polyposis patients. Cancer Epidemiol Biomarkers Prev. 2004;13(6):920–927.PubMedGoogle Scholar
  55. 55.
    Vereide AB, Kaino T, Sager G, Orbo A. Scottish Gynaecological Clinical Trials Group. Bcl-2, BAX, and apoptosis in endometrial hyperplasia after high dose gestagen therapy: a comparison of responses in patients treated with intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol. 2005;97(3):740–750.PubMedCrossRefGoogle Scholar
  56. 56.
    Reed JC. Mechanisms of apoptosis avoidance in cancer. Curr Opin Oncol. 1999;11:68–75.PubMedCrossRefGoogle Scholar
  57. 57.
    Rodriguez GC, Walmer DK, Cline M, et al. Effect of progestin on the ovarian epithelium of macaques: cancer prevention through apoptosis? J Soc Gynecol Invest. 1998;5:271–276.CrossRefGoogle Scholar
  58. 58.
    Rodriguez GC, Nagarsheth NP, Lee KL, et al. Progestin-induced apoptosis in the macaque ovarian epithelium: differential regulation of transforming growth factor-β. J Natl Cancer Inst. 2002;94(1):50–60.PubMedGoogle Scholar
  59. 59.
    Sun SY, Yue P, Chen X, Hong WK, Lotan R. The synthetic retinoid CD437 selectively induces apoptosis in human lung cancer cells while sparing normal human lung epithelial cells. Cancer Res. 2002;62(8):2430–2436.PubMedGoogle Scholar
  60. 60.
    Sporn MB, Suh N. Chemoprevention of cancer. Carcinogenesis. 2000;21(3):525–530.PubMedCrossRefGoogle Scholar
  61. 61.
    Rosenberg L, Palmer JR, Zauber AG, et al. A case-control study of oral contraceptive use and invasive epithelial ovarian cancer. Am J Epidemiol. 1994;139:654–661.PubMedGoogle Scholar
  62. 62.
    Stanford JL, Thomas DB, Ray RM, et al. Epithelial ovarian cancer and combined oral contraceptives: the WHO collaborative study of neoplasia and steroid contraceptives. Int J Epidemiol. 1989;18:538–545.CrossRefGoogle Scholar
  63. 63.
    Lee NC, Wingo PA, Gwynn ML, et al. The reduction in risk of ovarian cancer associated with oral-contraceptive use. N Engl J Med. 1987;316:650–655.CrossRefGoogle Scholar
  64. 64.
    Gross TP, Schlesselmann JJ. The estimated effect of oral contraceptive use on the cumulative risk of epithelial ovarian cancer. Obstet Gynecol. 1994;83:419–424.PubMedGoogle Scholar
  65. 65.
    Franceschi S, Parazzini F, Negri E, et al. Pooled analysis of three European case-control studies of epithelial ovarian cancer: III. Oral contraceptive use. Int J Cancer. 1991;49:61–65.PubMedCrossRefGoogle Scholar
  66. 66.
    Reiss M. Transforming growth factor-beta and cancer: a love-hate relationship? Oncol Res. 1997;9:447–457.PubMedGoogle Scholar
  67. 67.
    Schildkraut JM, Calingaert B, Marchbanks PA, Moorman PG, Rodriguez GC. Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk. J Natl Cancer Inst. 2002;94(1):32–38.PubMedGoogle Scholar
  68. 68.
    Risch HA. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst. 1998;90:1774–1786.PubMedCrossRefGoogle Scholar
  69. 69.
    Whiteman DC, Siskind V, Purdie DM, Green AC. Timing of pregnancy and the risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2003;12:42–46.PubMedGoogle Scholar
  70. 70.
    Rostgaard K, Wohlfahrt J, Andersen PK, et al. Does pregnancy induce the shedding of premalignant ovarian cells? Epidemiology. 2003;14:168–173.PubMedCrossRefGoogle Scholar
  71. 71.
    Studzinski G, Moore D. Sunlight: can it prevent as well as cause cancer? Cancer Res. 1995;55:4012–4022.Google Scholar
  72. 72.
    Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79(3):362–371.PubMedGoogle Scholar
  73. 73.
    Gross MD. Vitamin D and calcium in the prevention of prostate and colon cancer: new approaches for the identification of needs. J Nutr. 2005;135(2):326–331.PubMedGoogle Scholar
  74. 74.
    Hanley DA, Davison KS. Vitamin D insufficiency in North America. J Nutr. 2005;135(2):332–337.PubMedGoogle Scholar
  75. 75.
    Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–281.PubMedCrossRefGoogle Scholar
  76. 76.
    Nesby-O'Dell S, Scanlon KS, Cogswell ME, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr. 2002;76(1):187–192.PubMedGoogle Scholar
  77. 77.
    Richardson JP. Vitamin D deficiency – the once and present epidemic. Am Fam Phys. 2005;71(2):241–242.Google Scholar
  78. 78.
    Vieth R. The pharmacology of vitamin D, including fortification strategies. In: Feldman P, Glorieux F, Pike JW, eds. Vitamin D. Amsterdam: Elsevier Inc.; 2005.Google Scholar
  79. 79.
    Bland R, Walker EA, Hughes SV, Stewart PM, Hewison M. Constitutive expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in a transformed human proximal tubule cell line: evidence for direct regulation of vitamin D metabolism by calcium. Endocrinology. 1999;140(5):2027–2034.PubMedCrossRefGoogle Scholar
  80. 80.
    Chen TC, Schwartz GG, Burnstein KL, Lokeshwar BL, Holick MF. The in vitro evaluation of 25-hydroxyvitamin D3 and 19-nor-1alpha,25-dihydroxyvitamin D2 as therapeutic agents for prostate cancer. Clin Cancer Res. 2000;6(3):901–908.PubMedGoogle Scholar
  81. 81.
    Correa P, Segersten U, Hellman P, Akerstrom G, Westin G. Increased 25-hydroxyvitamin D3 1alpha-hydroxylase and reduced 25-hydroxyvitamin D3 24-hydroxylase expression in parathyroid tumors – new prospects for treatment of hyperparathyroidism with vitamin d. J Clin Endocrinol Metab. 2002;87(12):5826–5829.PubMedCrossRefGoogle Scholar
  82. 82.
    Henry HL. The 25-hydroxyvitamin D 1-alpha hydroxylase. In: Feldman P, Pike JW, Glorieux F, eds. Vitamin D. Amsterdam: Elsevier Inc.; 2005.Google Scholar
  83. 83.
    Howard GA, Turner RT, Sherrard DJ, Baylink DJ. Human bone cells in culture metabolize 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3. J Biol Chem. 1981;256(15):7738–7740.PubMedGoogle Scholar
  84. 84.
    Hsu JY, Feldman D, McNeal JE, Peehl DM. Reduced 1alpha-hydroxylase activity in human prostate cancer cells correlates with decreased susceptibility to 25-hydroxyvitamin D3-induced growth inhibition. Cancer Res. 2001;61(7):2852–2856.PubMedGoogle Scholar
  85. 85.
    Huang DC, Papavasiliou V, Rhim JS, Horst RL, Kremer R. Targeted disruption of the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in ras-transformed keratinocytes demonstrates that locally produced 1alpha,25-dihydroxyvitamin D3 suppresses growth and induces differentiation in an autocrine fashion. Mol Cancer Res. 2002;1(1):56–67.PubMedGoogle Scholar
  86. 86.
    Schwartz GG, Whitlatch LW, Chen TC, Lokeshwar BL, Holick MF. Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. Cancer Epidemiol Biomarkers Prev. 1998;7(5):391–395.PubMedGoogle Scholar
  87. 87.
    Segersten U, Holm PK, Björklund P, et al. 25-Hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of non-1alpha-hydroxylated vitamin D analogue. Breast Cancer Res. 2005;7(6):R980–R986.PubMedCrossRefGoogle Scholar
  88. 88.
    Tangpricha V, Flanagan JN, Whitlatch LW, et al. 25-hydroxyvitamin D-1alpha-hydroxylase in normal and malignant colon tissue. Lancet. 2001;357(9269):1673–1674.PubMedCrossRefGoogle Scholar
  89. 89.
    Young MV, Schwartz GG, Wang L, et al. The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D. Carcinogenesis. 2004;25(6):967–971.PubMedCrossRefGoogle Scholar
  90. 90.
    Zehnder D, Bland R, Walker EA, et al. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in the human kidney. J Am Soc Nephrol. 1999;10(12):2465–2473.PubMedGoogle Scholar
  91. 91.
    Zehnder D, Bland R, Williams MC, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001;86(2):888–894.PubMedCrossRefGoogle Scholar
  92. 92.
    Bouillon R. Vitamin D: from photosynthesis, metabolism, and action to clinical applications. In: DeGroot LJ, Jameson JL, eds. Endocrinology. Philadelphia: W.B. Saunders; 2001:1009–1028.Google Scholar
  93. 93.
    Dusso AS, Brown AJ, Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol. 2005;289(1):F8–28.PubMedCrossRefGoogle Scholar
  94. 94.
    Holick MF, Garabedian M. Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Washington, DC: American Society for Bone and Mineral Research; 2006:129–137.Google Scholar
  95. 95.
    Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev. 2005;26(5):662–687.PubMedCrossRefGoogle Scholar
  96. 96.
    Bailey R, Cooper JD, Zeitels L, et al. Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes. 2007;56(10):2616–2621.PubMedCrossRefGoogle Scholar
  97. 97.
    Gezen-Ak D, Dursun E, Ertan T, et al. Association between vitamin D receptor gene polymorphism and Alzheimer's disease. Tohoku J Exp Med. 2007;212(3):275–282.PubMedCrossRefGoogle Scholar
  98. 98.
    Horst-Sikorska W, Kalak R, Wawrzyniak A, Marcinkowska M, Celczynska-Bajew L, Slomski R. Association analysis of the polymorphisms of the VDR gene with bone mineral density and the occurrence of fractures. J Bone Miner Metab. 2007;25(5):310–319.PubMedCrossRefGoogle Scholar
  99. 99.
    Kuningas M, Mooijaart SP, Jolles J, Slagboom PE, Westendorp RG, van Heemst D. VDR gene variants associate with cognitive function and depressive symptoms in old age. Neurobiol Aging. 2009;30(3):466–73.Google Scholar
  100. 100.
    Li H, Stampfer MJ, Hollis JBW, et al. A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med. 2007;4(3):e103.PubMedCrossRefGoogle Scholar
  101. 101.
    Obara W, Suzuki Y, Kato K, Tanji S, Konda R, Fujioka T. Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese population. Int J Urol. 2007;14(6):483–487.PubMedCrossRefGoogle Scholar
  102. 102.
    Patiño-García B, Arroyo C, Rangel-Villalobos H, et al. Association between polymorphisms of the androgen and vitamin D receptor genes with prostate cancer risk in a Mexican population. Rev Invest Clin. 2007;59(1):25–31.PubMedGoogle Scholar
  103. 103.
    Purdue MP, Hartge P, Davis S, et al. Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma. Cancer Causes Control. 2007;18(9):989–999.PubMedCrossRefGoogle Scholar
  104. 104.
    Purdue MP, Lan Q, Kricker A, Vajdic CM, Rothman N, Armstrong BK. Vitamin D receptor gene polymorphisms and risk of non-Hodgkin's lymphoma. Haematologica. 2007;92(8):1145–1146.PubMedCrossRefGoogle Scholar
  105. 105.
    Ramos-Lopez E, Bruck P, Jansen T, Herwig J, Badenhoop K. CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans. Diabetes Metab Res Rev. 2007;23(8):631–636.PubMedCrossRefGoogle Scholar
  106. 106.
    Grant WB, Garland CF, Holick MF. Comparisons of estimated economic burdens due to insufficient solar ultraviolet irradiance and vitamin D and excess solar UV irradiance for the United States. Photochem Photobiol. 2005;81(6):1276–1286.PubMedCrossRefGoogle Scholar
  107. 107.
    Berube S, Diorio C, Verhoek-Oftedahl W, Brisson J. Vitamin D, calcium, and mammographic breast densities. Cancer Epidemiol Biomarkers Prev. 2004;13(9):1466–1472.PubMedGoogle Scholar
  108. 108.
    Feskanich D, Ma J, Fuchs CS, et al. Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev. 2004;13(9):1502–1508.PubMedGoogle Scholar
  109. 109.
    Garland CF, Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96(2):252–261.PubMedCrossRefGoogle Scholar
  110. 110.
    Giovannucci E, Liu-Y, Rimm-E-B, et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006;98(7):451–459.PubMedCrossRefGoogle Scholar
  111. 111.
    Welsh J, Wietzke JA, Zinser GM, Byrne B, Smith K, Narvaez CJ. Vitamin D-3 receptor as a target for breast cancer prevention. J Nutr. 2003;133(7 Suppl):2425S–2433S.PubMedGoogle Scholar
  112. 112.
    Lefkowitz ES, Garland CF. Sunlight, vitamin D, and ovarian cancer mortality rates in US women. Int J Epidemiol. 1994;23(6):1133–1136.PubMedCrossRefGoogle Scholar
  113. 113.
    Choi KC, Kang SK, Tai CJ, Auersperg N, Leung PCK. The regulation of apoptosis by activin and transforming growth factor-beta in early neoplastic and tumorigenic ovarian surface epithelium. J Clin Endocrinol Metab. 2001;86(5):2125–2135.PubMedCrossRefGoogle Scholar
  114. 114.
    Feng J, Junying B, Pengfei L, Santo VN, Wenlong B. Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase. J Biol Chem. 2004;279(51):53213–53221.CrossRefGoogle Scholar
  115. 115.
    Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez Lira-Lira G, Escudero-De los Rios P, Hernandez-Avila M. Nutritional determinants of epithelial ovarian cancer risk: a case-control study in Mexico. Oncology. 2002;63(2):151–157.PubMedCrossRefGoogle Scholar
  116. 116.
    Kashfi K, Rigas B. Non-Cox-2 targets and cancer: expanding the molecular target repertoire of chemoprevention. Biochem Pharm. 2005;70;969–986PubMedCrossRefGoogle Scholar
  117. 117.
    Cramer D, Harlow B, Titus-Ernstoff L, Bohlke K, Welch W, Greenberg E. Over-the-counter analgesics and risk of ovarian cancer. Lancet. 1998;351:104–107.PubMedCrossRefGoogle Scholar
  118. 118.
    Moyisch K, Mettlllin C, Piver M, Natarajan N, Menezes R, Swede H. Regular use of analgesic drugs and ovarian cancer risk. Cancer Epidemiol Biomarkers Prev. 2001;10:903–906.Google Scholar
  119. 119.
    Rosenberg L, Palmer J, Rao R, et al. A case-control study of analgesic use and ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2000;9:933–937.PubMedGoogle Scholar
  120. 120.
    Tavani A, Gallus S, La Vecchia C, Conti E, Montella M, Franceschi S. Aspirin and ovarian cancer: an Italian case-control study. Ann Oncol. 2001;11:1171–1173.CrossRefGoogle Scholar
  121. 121.
    Hannibal CG, Rossing MA, Wicklund KG, Cushing-Haugen KL. Analgesic use and risk of epithelial ovarian cancer. Am J Epidemiol. 2008;167:1430–1437PubMedCrossRefGoogle Scholar
  122. 122.
    Schildkraut JM, Moorman PG, Halabi S, Calingert B, Marks JR, Berchuck A. Analgesic use and risk of ovarian cancer. Epidemiology. 2006;17:104–107.PubMedCrossRefGoogle Scholar
  123. 123.
    Earnest D, Hixson I, Alberts D. Piroxicam and other cyclooxygenase inhibitors: potential for cancer prevention. J Cell Biochem Suppl. 1992;161:156.CrossRefGoogle Scholar
  124. 124.
    Goodwin J. Prostaglandins and host defense in cancer. Med Clin North Am. 1981;65:829–844.PubMedGoogle Scholar
  125. 125.
    Marnett L. Aspirin and related nonsteroidal anti-inflammatory drugs as chemopreventive agents against colon cancer. Prev Med. 2001;33:682–687.CrossRefGoogle Scholar
  126. 126.
    Rodriguez-Buford C, Barnes M, Oelschlager D, et al. Effects of nonsteroidal anti-inflammatory agents (NSAIDs) on ovarian carcinoma cell lines: preclinical evaluation of NSAIDs as chemopreventive agents. Clin Cancer Res. 2001;8:202–209.Google Scholar
  127. 127.
    Vital-Reyes V, Rodriguez-Buford C, Chhieng DC, et al. Celecoxib inhibits cellular growth, decreases Ki67 expression and modifies apoptosis in ovarian cancer cell lines. Arch Med Res. 2006;37(6):689–695.PubMedCrossRefGoogle Scholar
  128. 128.
    Kim J-S, Baek SJ, Sali T, Eling TE. The conventional nonsteroidal anti-inflammatory drug sulindac sulfide arrests ovarian cancer cell growth via the expression of NAG-1/MIC-1/GDF-15. Mol Cancer Ther. 2005;4(3):487–493.PubMedGoogle Scholar
  129. 129.
    Niles R. Signaling pathways in retinoid chemoprevention and treatment of cancer. Mutat Res. 2004;555:81–86.PubMedGoogle Scholar
  130. 130.
    Brewer MA, Mitchell MF, Bast RC. Prevention of ovarian cancer. In Vivo 1999;13:99–106.PubMedGoogle Scholar
  131. 131.
    Um S-J, Lee S-Y, Kim E-J, et al. Anti-proliferative mechanism of retinoid derivatives in ovarian cancer cells. Cancer Lett. 2001;174:127–134.PubMedCrossRefGoogle Scholar
  132. 132.
    Zhang D, Holmes WF, Wu S, Soprano DR, Soprano KJ. Retinoids and ovarian cancer. J Cell Physiol. 2000;185:1–20.PubMedCrossRefGoogle Scholar
  133. 133.
    Formelli F, Cleris L. Synthetic retinoid fenretinamide is effective against a human ovarian carcinoma xenograft and potentiates cisplatin activity. Cancer Res. 1993;53:5374–5376.PubMedGoogle Scholar
  134. 134.
    Guruswamy S, Lightfoot S, Gold MA, et al. Effects of retinoids on cancerous phenotype and apoptosis in organotypic cultures of ovarian carcinoma. J Natl Cancer Inst (Bethesda). 2001;93:516–525.CrossRefGoogle Scholar
  135. 135.
    Wu S, Zhang D, Donigan A, Dawson MI, Soprano DR, Soprano KJ. Effects of conformationally restricted synthetic retinoids on ovarian tumor cell growth. J Cell Biochem. 1998;68:378–388.PubMedCrossRefGoogle Scholar
  136. 136.
    Dabal R, Boyer CM, Berchuck A, et al. Synergistic inhibition of ovarian cancer cell proliferation by TGFß and retinoic acid (RA) derivatives. Proc Am Assoc Cancer Res. 1995;36:635.Google Scholar
  137. 137.
    Oridate N, Suzuki S, Higuchi M, Mitchell M, Hong W, Lotan R. Involvement of reactive oxygen species in N-(4-hydroxyphenyl) retinamide-induced apoptosis in cervical carcinoma cells. J Natl Cancer Inst (Bethesda). 1997;89:1191–1198.CrossRefGoogle Scholar
  138. 138.
    Brewer M, Utzinger U, Satterfield W, et al. Biomarker modulation in a nonhuman rhesus primate model for ovarian cancer prevention. Cancer Epidemiol Biomarkers Prev. 2001;10:889–893.PubMedGoogle Scholar
  139. 139.
    De Palo G, Veronesi U, Camerini T, et al. Can fenretinide protect women against ovarian cancer. J Natl Cancer Inst. 1995;87:146–147.PubMedCrossRefGoogle Scholar
  140. 140.
    De Palo G, Mariani L, Camerini T, et al. Effect of fenretinide on ovarian carcinoma occurrence. Gynecol Oncol. 2002;86:24–27.PubMedCrossRefGoogle Scholar
  141. 141.
    Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275:218–220.PubMedCrossRefGoogle Scholar
  142. 142.
    Kundu J, Surh Y. Molecular basis of chemoprevention by resveratrol: NF-κB and AP-1 as potential targets. Mutat Res. 2004;555:65–80.PubMedGoogle Scholar
  143. 143.
    Webb PM, Purdie DM, Bain CJ, Green AC. Alcohol, wine, and risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2004;13:592–599.PubMedGoogle Scholar
  144. 144.
    Larsson SC, Giovannucci E, Wolk A. Dietary folate intake and incidence of ovarian cancer: the Swedish Mammography Cohort. J Natl Cancer Inst. 2004;96:396–402.PubMedCrossRefGoogle Scholar
  145. 145.
    Cornwell T, Cohick W, Raskin I. Dietary phytoestrogens and health. Phytochemistry. 2004;65:995–1016.PubMedCrossRefGoogle Scholar
  146. 146.
    Lampe JW, Peterson S. Brassica, biotransformation and cancer risk: genetic polymorphisms alter the preventive effects of cruciferous vegetables. J Nutr. 2002;132:2991–2994.PubMedGoogle Scholar
  147. 147.
    Bradlow HL, Sepkovic DW, Telang NT, et al. Multifunctional aspects of the action of indole-3-carbinol as an antitumor agent. Ann NY Acad Sci. 1999;889:204–213.PubMedCrossRefGoogle Scholar
  148. 148.
    Auborn KJ, Fan S, Rosen EM, et al. Indole-3-carbinol is a negative regulator of estrogen. J Nutr. 2003;133(Suppl):2470S–2475S.PubMedGoogle Scholar
  149. 149.
    Block G, Patterson B, Subar A. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer. 1992;18:1–29.PubMedCrossRefGoogle Scholar
  150. 150.
    Syed D, Afaq F, Mukhtar H. Pomegranate derived products for cancer chemoprevention. Sem Cancer Biol. 2007;17:377–385.CrossRefGoogle Scholar
  151. 151.
    Ding H, Chin Y, Kinghorn D, Ambrosio S. Chemopreventive characteristics of avocado fruit. Semin Cancer Biol. 2007;17:386–394.PubMedCrossRefGoogle Scholar
  152. 152.
    Piver M. Epidemiologic perspective of ovarian cancer. In: Sciarra, J.J. (2008). The Global library of women's medicine. London: Sapiens Global Library Limited.
  153. 153.
    Hou Z, Lambert J, Chin K, Yang C. Effect of tea polyphenols on signal transduction pathways related to cancer chemoprevention. Mutat Res. 2004;555:3–19.PubMedGoogle Scholar
  154. 154.
    Sarkar F, Li Y. Cell signaling pathways altered by natural chemopreventive agents. Mutat Res. 2004;555:53–64.PubMedGoogle Scholar
  155. 155.
    Nichenametla S, Taruscio T, Barney D, Exon J. A review of the effects and mechanisms of polyphenolics in cancer. Crit Rev Food Sci Nutr. 2006;46:161–183.PubMedCrossRefGoogle Scholar
  156. 156.
    Chen X, Anderson JJ. Isoflavones inhibit proliferation of ovarian cancer cells in vitro via an estrogen receptordependent pathway. Nutr Cancer. 2001;41:165–171.PubMedCrossRefGoogle Scholar
  157. 157.
    Chang ET, Lee VS, Canchola AJ, et al. Diet and risk of ovarian cancer in the California Teachers Study Cohort. Am J Epidemiol. 2007;165(7):802–813.Google Scholar
  158. 158.
    Simopoulos A. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr. 1991;54:438–463.PubMedGoogle Scholar
  159. 159.
    Burns CP, Halabi S, Clamon G, et al. Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia. Cancer. 2004;101(2):370–378.PubMedCrossRefGoogle Scholar
  160. 160.
    La Vecchia C, Decarli A, Negri E, et al. Dietary factors and the risk of epithelial ovarian cancer. J Natl Cancer Inst. 1987;79(4):663–669.PubMedGoogle Scholar
  161. 161.
    Bosetti C, Negri E, Franceschi S, et al. Diet and ovarian cancer risk: a case-control study in Italy. Int J Cancer. 2001;93(6):911–915.PubMedCrossRefGoogle Scholar
  162. 162.
    Hunter JE. n-3 fatty acids from vegetable oils. Am J Clin Nutr. 1990;51:809–814.PubMedGoogle Scholar
  163. 163.
    World Cancer Research Fund, American Institute for Cancer Research. Food, Nutrition and the Prevention of Cancer: A Global Perspective. Washington, DC: American Institute for Cancer Research; 1997:452–459.Google Scholar
  164. 164.
    Fernandez E, Chatenoud L, La Vecchia C, Negri E, Franceschi S. Fish consumption and cancer risk. Am J Clin Nutr. 1999;70(1):85–90.PubMedGoogle Scholar
  165. 165.
    Sharma A, Belna J, Logan J, Espat J, Hurteau JA. The effects of omega-3 fatty acids on growth regulation of epithelial ovarian cancer cell lines. Gynecol Oncol. 2005;99(1):58–64.PubMedCrossRefGoogle Scholar
  166. 166.
    Sharma A, Belna J, Espat J, Cannon V, Hurteau JA. Omega-3 fatty acids augment components of the TGF-β1 pathway in ovarian cancer cells; implication for dietary modification and prevention. Am J Obstet Gynecol. 2009;200(5):516.e1–516.e6.Google Scholar
  167. 167.
    Sporn MB. Hobson's choice and the need for combinations of new agents for the prevention and treatment of breast cancer. J Natl Cancer Inst. 2002;94:242–243.PubMedGoogle Scholar
  168. 168.
    Lieberman R. Chemoprevention of prostate cancer: current status and future directions. Cancer Metastasis Rev. 2002;21:297–309.PubMedCrossRefGoogle Scholar
  169. 169.
    Barnes MN, Berry WD, Straughn JM, et al. A pilot study of ovarian cancer chemoprevention using medroxyprogesterone acetate in an avian model of spontaneous ovarian carcinogenesis. Gynecol Oncol. 2002;87:57–63.PubMedCrossRefGoogle Scholar
  170. 170.
    Nishida T, Sugiyama T, Katabuchi H, Yakushiji M, Kato T. Histologic origin of rat ovarian cancer induced by direct application of 7,12-dimethylbenz(a)anthracene. Nippon Sanka Fujinka Gakkai Zasshi. 1986;38:570–574.PubMedGoogle Scholar
  171. 171.
    Silva EG, Tornos C, Deavers M, Kaisman K, Gray K, Gershenson D. Induction of epithelial neoplasms in the ovaries of guinea pigs by estrogenic stimulation. Gynecol Oncol. 1998;71:240–246.PubMedCrossRefGoogle Scholar
  172. 172.
    Silva EG, Tornos C, Fritsche HA Jr, et al. The induction of benign epithelial neoplasms of the ovaries of guinea pigs by testosterone stimulation: a potential animal model. Mod Pathol. 1997;10:879–883.PubMedGoogle Scholar
  173. 173.
    Testa JR, Getts LA, Salazar H, et al. Spontaneous transformation of rat ovarian surface epithelial cells results in well to poorly differentiated tumors with a parallel range of cytogenetic complexity. Cancer Res. 1994;54:2778–2784.PubMedGoogle Scholar
  174. 174.
    Boyd J. Mouse models of gynecologic pathology. N Engl J Med. 2005;352:2240–2242.PubMedCrossRefGoogle Scholar
  175. 175.
    Connolly DC, Bao R, Nikitin AY, et al. Female mice chimeric for expression of the simian virus 40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Res. 2003;63:1389–1397.PubMedGoogle Scholar
  176. 176.
    Dinulescu DM, Ince TA, Quade BJ, Shafer SA, Crowley D, Jacks T. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med. 2005;11:63–70.PubMedCrossRefGoogle Scholar
  177. 177.
    Flesken-Nikitin A, Choi KC, Eng JP, Shmidt EN, Nikitin AY. Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium. Cancer Res. 2003;63:3459–3463.PubMedGoogle Scholar
  178. 178.
    Kiguchi K, Kubota T, Aoki D, et al. A patient-like orthotopic implantation nude mouse model of highly metastatic human ovarian cancer. Clin Exp Metastasis. 1998;16:751–756.PubMedCrossRefGoogle Scholar
  179. 179.
    Fredrickson TN. Ovarian tumors of the hen. Environ Health Perspect. 1987;73:35–51.PubMedCrossRefGoogle Scholar
  180. 180.
    Wilson JE. Adeno-carcinomata in hens kept in a constant environment. Poult Sci. 1958;37:1253.Google Scholar
  181. 181.
    Crist KA, Zhang Z, You M, et al. Characterization of rat ovarian adenocarcinomas developed in response to direct instillation of 7,12-dimethylbenz[a]anthracene (DMBA) coated suture. Carcinogenesis. 2005;26:951.PubMedCrossRefGoogle Scholar
  182. 182.
    Fu X, Hoffman RM. Human ovarian carcinoma metastatic models constructed in nude mice by orthotopic transplantation of histologically-intact patient specimens. Anticancer Res. 1993;13:283–286.PubMedGoogle Scholar
  183. 183.
    Hamilton TC, Young RC, Louie KG, et al. Characterization of a xenograft model of human ovarian carcinoma which produces ascites and intraabdominal carcinomatosis in mice. Cancer Res. 1984;44:5286–5290.PubMedGoogle Scholar
  184. 184.
    Liu J, Yang G, Thompson-Lanza JA, et al. A genetically defined model for human ovarian cancer. Cancer Res. 2004;64:1655–1663.PubMedCrossRefGoogle Scholar
  185. 185.
    Repasky EA, Tims E, Pritchard M, Burd R. Characterization of mild whole-body hyperthermia protocols using human breast, ovarian, and colon tumors grown in severe combined immunodeficient mice. Infect Dis Obstet Gynecol. 1999;7:91–97.PubMedCrossRefGoogle Scholar
  186. 186.
    Rose GS, Tocco LM, Granger GA, et al. Development and characterization of a clinically useful animal model of epithelial ovarian cancer in the Fischer 344 rat. Am J Obstet Gynecol. 1996;175:593–599.PubMedCrossRefGoogle Scholar
  187. 187.
    Sallinen H, Anttila M, Narvainen J, et al. A highly reproducible xenograft model for human ovarian carcinoma and application of MRI and ultrasound in longitudinal follow-up. Gynecol Oncol. 2006;103:315–320.PubMedCrossRefGoogle Scholar
  188. 188.
    Shaw TJ, Senterman MK, Dawson K, Crane CA, Vanderhyden BC. Characterization of intraperitoneal, orthotopic, and metastatic xenograft models of human ovarian cancer. Mol Ther. 2004;10:1032–1042.PubMedCrossRefGoogle Scholar
  189. 189.
    Stakleff KD, Von Gruenigen VE. Rodent models for ovarian cancer research. Int J Gynecol Cancer. 2003;13:405–412.PubMedCrossRefGoogle Scholar
  190. 190.
    Stewart SL, Querec TD, Ochman AR, et al. Characterization of a carcinogenesis rat model of ovarian preneoplasia and neoplasia. Cancer Res. 2004;64:8177–8183.PubMedCrossRefGoogle Scholar
  191. 191.
    Vanderhyden BC, Shaw TJ, Ethier JF. Animal models of ovarian cancer. Reprod Biol Endocrinol. 2003;1:67.PubMedCrossRefGoogle Scholar
  192. 192.
    Xu Y, Silver DF, Yang NP, et al. Characterization of human ovarian carcinomas in a SCID mouse model. Gynecol Oncol. 1999;72:161–170.PubMedCrossRefGoogle Scholar
  193. 193.
    Yoshida Y, Kamitani N, Sasaki H, Kusumi K, Tominaga T, Kotsuji F. Establishment of a liver metastatic model of human ovarian cancer. Anticancer Res. 1998;18:327–331.PubMedGoogle Scholar
  194. 194.
    Rodriguez GC, Carver D, Anderson K. Evaluation of ovarian cancer preventive agents in the chicken. Gynecol Oncol. 2001;80:317.CrossRefGoogle Scholar
  195. 195.
    Hakim AA, Barry CP, Barnes HJ, et al. Ovarian adenocarcinomas in the laying hen & women have similar alterations in p53, ras, & HER-2/neu. Cancer Prev Res. 2009;2(2):114–121.Google Scholar
  196. 196.
    Hogdall EV, Christensen L, Kjaer SK, et al. Distribution of HER-2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma: from the Danish MALOVA Ovarian Cancer Study. Cancer 2003;98:66–73.PubMedCrossRefGoogle Scholar
  197. 197.
    Nielsen JS, Jakobsen E, Holund B, Bertelsen K, Jakobsen A. Prognostic significance of p53, Her-2, and EGFR overexpression in borderline and epithelial ovarian cancer. Int J Gynecol Cancer. 2004;14:1086–1096.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Division of Gynecologic OncologyNorthShore University HealthSystemEvanstonUSA

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