Cancer Causes & Control

, Volume 20, Issue 9, pp 1539–1550 | Cite as

Promoter methylation and the detection of breast cancer

  • Jennifer Brooks
  • Paul Cairns
  • Anne Zeleniuch-Jacquotte
Review article

Abstract

Mammographic screening has been shown to reduce breast cancer mortality in women over the age of 50 years, and to a lesser extent in younger women. The sensitivity of mammography, however, is reduced in some groups of women. There remains a need for a minimally invasive, cost-effective procedure that could be used along side mammography to improve screening sensitivity. Silencing of tumor suppressor genes through promoter hypermethylation is known to be a frequent and early event in carcinogenesis. Further, changes in methylation patterns observed in tumors are also detectable in the circulation of women with breast cancer. This makes these alterations candidate markers for early tumor detection. In this paper, we review the current literature on promoter hypermethylation changes and breast cancer and discuss issues that remain to be addressed in order for the potential of these markers to augment the sensitivity of screening mammography. In general, studies in well-defined populations, including appropriate controls and larger numbers are needed. Further, focus on the optimization of methods of methylation detection in small amounts of DNA is needed.

Keywords

Breast neoplasms Early detection of cancer DNA methylation 

References

  1. 1.
    Ries L, Melbert D, Krapcho M, Mariotto A, Miller B, Feuer E et al (2006) SEER cancer statistics review, 1975–2004. National Cancer Institute, BethesdaGoogle Scholar
  2. 2.
    Etzioni R, Urban N, Ramsey S, McIntosh M, Schwartz S, Reid B et al (2003) The case for early detection. Nat Rev Cancer 3(4):243–252CrossRefPubMedGoogle Scholar
  3. 3.
    Helme S, Pemy N, Mokbel K (2006) Screening mammography in women aged 40–49: is it time to change? Int Semin Surg Oncol 3(1):4CrossRefPubMedGoogle Scholar
  4. 4.
    Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L (2006) Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’ follow-up: a randomised controlled trial. Lancet 368(9552):2053–2060CrossRefPubMedGoogle Scholar
  5. 5.
    Norman S, Russell Localio A, Weber A, Coates R, Zhou L, Bernstein L et al (2007) Protection of mammography screening against death from breast cancer in women aged 40–64 years. Cancer Causes Control 18(9):909–918CrossRefPubMedGoogle Scholar
  6. 6.
    Cancer Trends Progress Report—2007 Update (2007) National Cancer Institute, NIH, DHHS, Bethesda, MD, December 2007, http://progresspreportcancergov
  7. 7.
    Weir HK, Thun MJ, Hankey BF, Ries LAG, Howe HL, Wingo PA et al (2003) Annual report to the nation on the status of cancer, 1975–2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst 95(17):1276–1299PubMedGoogle Scholar
  8. 8.
    Elmore JG, Armstrong K, Lehman CD, Fletcher SW (2005) Screening for breast cancer. JAMA 293(10):1245–1256CrossRefPubMedGoogle Scholar
  9. 9.
    Levenson VV (2007) Biomarkers for early detection of breast cancer: what, when, and where? Biochimica et Biophysica Acta (BBA) 1770(6):847–856Google Scholar
  10. 10.
    Berg WA, Gutierrez L, NessAiver MS, Carter WB, Bhargavan M, Lewis RS et al (2004) Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology 233(3):830–849CrossRefPubMedGoogle Scholar
  11. 11.
    Evans A (2002) Hormone replacement therapy and mammographic screening. Clin Radiol 57(7):563–564CrossRefPubMedGoogle Scholar
  12. 12.
    Zhi H, Ou B, Luo B-M, Feng X, Wen Y-L, Yang H-Y (2007) Comparison of ultrasound elastography, mammography, and sonography in the diagnosis of solid breast lesions. J Ultrasound Med 26(6):807–815PubMedGoogle Scholar
  13. 13.
    Maskarinec G, Meng L, Ursin G (2001) Ethnic differences in mammographic densities. Int J Epidemiol 30(5):959–965CrossRefPubMedGoogle Scholar
  14. 14.
    Krecke K, Gisvold J (1993) Invasive lobular carcinoma of the breast: mammographic findings and extent of disease at diagnosis in 184 patients. Am J Roentgenol 161:957–960Google Scholar
  15. 15.
    Boetes C, Veltman J, van Die L, Bult p, Wobbes T, Barentsz J (2004) The role of MRI in invasive lobular carcinoma. Breast Cancer Res Treat 86(1):31–37CrossRefPubMedGoogle Scholar
  16. 16.
    Elmore JG, Barton MB, Moceri VM, Polk S, Arena PJ, Fletcher SW (1998) Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med 338(16):1089–1096CrossRefPubMedGoogle Scholar
  17. 17.
    Ernster V, Barclay J (1997) Increases in ductal carcinoma in situ (DCIS) of the breast in relation to mammography: a dilemma. J Natl Cancer Inst Monogr 22:151–156PubMedGoogle Scholar
  18. 18.
    Ma H, Hill C, Bernstein L, Ursin G (2008) Low-dose medical radiation exposure and breast cancer risk in women under age 50 years overall and by estrogen and progesterone receptor status: results from a case–control and a case–case comparison. Breast Cancer Res Treat 109(1):77–90CrossRefPubMedGoogle Scholar
  19. 19.
    Esteller M (2008) Epigenetics in cancer. N Engl J Med 358(11):1148–1159CrossRefPubMedGoogle Scholar
  20. 20.
    Esteller M, Herman J (2002) Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol 196(1):1–7CrossRefPubMedGoogle Scholar
  21. 21.
    Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3(6):415PubMedGoogle Scholar
  22. 22.
    Takai D, Jones PA (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci 99(6):3740–3745CrossRefPubMedGoogle Scholar
  23. 23.
    Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128(4):683–692CrossRefPubMedGoogle Scholar
  24. 24.
    Fackler MJ, McVeigh M, Mehrotra J, Blum MA, Lange J, Lapides A et al (2004) Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res 64(13):4442–4452CrossRefPubMedGoogle Scholar
  25. 25.
    Widschwendter M, Jones PA (2002) DNA methylation and breast carcinogenesis. Oncogene 21:5462–5482CrossRefPubMedGoogle Scholar
  26. 26.
    Esteller M (2007) Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum Mol Genet 16(R1):R50–R59CrossRefPubMedGoogle Scholar
  27. 27.
    Mandel P, Metais P (1948) Les acides nucleiques du plasma sanguin chez l’homme. CR Acad Sci Paris 142:241–243Google Scholar
  28. 28.
    Tsang JCH, Lo YMD (2007) Circulating nucleic acids in plasma/serum. Pathology 39(2):197–207CrossRefPubMedGoogle Scholar
  29. 29.
    Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S et al (2005) Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci USA 102(45):16368–16373CrossRefPubMedGoogle Scholar
  30. 30.
    Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch R-D et al (2001) DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 61(4):1659–1665PubMedGoogle Scholar
  31. 31.
    Cairns P, Sidransky D (1999) Molecular methods for the diagnosis of cancer. Biochimica et Biophysica Acta (BBA) 1423(2):11–18CrossRefGoogle Scholar
  32. 32.
    Tokumaru Y, Harden SV, Sun D-I, Yamashita K, Epstein JI, Sidransky D (2004) Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma. Clin Cancer Res 10(16):5518–5522CrossRefPubMedGoogle Scholar
  33. 33.
    Hoque MO, Topaloglu O, Begum S, Henrique R, Rosenbaum E, Van Criekinge W et al (2005) Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects. J Clin Oncol 23(27):6569–6575CrossRefPubMedGoogle Scholar
  34. 34.
    Dulaimi E, Uzzo RG, Greenberg RE, Al-Saleem T, Cairns P (2004) Detection of bladder cancer in urine by a tumor suppressor gene hypermethylation panel. Clin Cancer Res 10(6):1887–1893CrossRefPubMedGoogle Scholar
  35. 35.
    Hoque MO, Begum S, Topaloglu O, Chatterjee A, Rosenbaum E, Van Criekinge W et al (2006) Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection. J Natl Cancer Inst 98(14):996–1004PubMedGoogle Scholar
  36. 36.
    Leung W, To K-F, Chu E, Chan M, Bai A, Ng E et al (2005) Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer. Br J Cancer 92:2190–2194CrossRefPubMedGoogle Scholar
  37. 37.
    Hoque MO, Begum S, Topaloglu O, Jeronimo C, Mambo E, Westra WH et al (2004) Quantitative detection of promoter hypermethylation of multiple genes in the tumor, urine, and serum DNA of patients with renal cancer. Cancer Res 64(15):5511–5517CrossRefPubMedGoogle Scholar
  38. 38.
    Ibanez de Caceres I, Battagli C, Esteller M, Herman JG, Dulaimi E, Edelson MI et al (2004) Tumor cell-specific BRCA1 and RASSF1A hypermethylation in serum, plasma, and peritoneal fluid from ovarian cancer patients. Cancer Res 64(18):6476–6481CrossRefPubMedGoogle Scholar
  39. 39.
    Zou H-Z, Yu B-M, Wang Z-W, Sun J-Y, Cang H, Gao F et al (2002) Detection of aberrant p16 methylation in the serum of colorectal cancer patients. Clin Cancer Res 8(1):188–191PubMedGoogle Scholar
  40. 40.
    Wisman GBA, Nijhuis ER, Hoque MO, Reesink-Peters N, Koning AJ, Volders HH et al (2006) Assessment of gene promoter hypermethylation for detection of cervical neoplasia. Int J Cancer 119(8):1908–1914CrossRefPubMedGoogle Scholar
  41. 41.
    Fujiwara K, Fujimoto N, Tabata M, Nishii K, Matsuo K, Hotta K et al (2005) Identification of epigenetic aberrant promoter methylation in serum DNA is useful for early detection of lung cancer. Clin Cancer Res 11(3):1219–1225PubMedGoogle Scholar
  42. 42.
    Palmisano WA, Divine KK, Saccomanno G, Gilliland FD, Baylin SB, Herman JG et al (2000) Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res 60(21):5954–5958PubMedGoogle Scholar
  43. 43.
    Schmiemann V, Bocking A, Kazimirek M, Onofre ASC, Gabbert HE, Kappes R et al (2005) Methylation assay for the diagnosis of lung cancer on bronchial aspirates: a cohort study. Clin Cancer Res 11(21):7728–7734CrossRefPubMedGoogle Scholar
  44. 44.
    Zhang Y-J, Wu H-C, Shen J, Ahsan H, Tsai WY, Yang H-I et al (2007) Predicting hepatocellular carcinoma by detection of aberrant promoter methylation in serum DNA. Clin Cancer Res 13(8):2378–2384CrossRefPubMedGoogle Scholar
  45. 45.
    Novak p, Jensen TJ, Garbe JC, Stampfer MR, Futscher BW (2009) Stepwise DNA methylation changes are linked to escape from defined proliferation barriers and mammary epithelial cell immortalization. Cancer Res 69(12):5251–5258CrossRefPubMedGoogle Scholar
  46. 46.
    Fackler M, McVeigh M, Evron E, Garrett E, Mehrotra J, Polyak K et al (2003) DNA methylation of RASSF1A, HIN-1, RAR-b, Cyclin D2 and TWIST in in situ and invasive lobular breast carcinoma. Int J Cancer 107(6):970–975CrossRefPubMedGoogle Scholar
  47. 47.
    Parrella p, Poeta ML, Gallo AP, Prencipe M, Scintu M, Apicella A et al (2004) Nonrandom distribution of aberrant promoter methylation of cancer-related genes in sporadic breast tumors. Clin Cancer Res 10(16):5349–5354CrossRefPubMedGoogle Scholar
  48. 48.
    Jeronimo C, Costa I, Martins MC, Monteiro P, Lisboa S, Palmeira C et al (2003) Detection of gene promoter hypermethylation in fine needle washings from breast lesions. Clin Cancer Res 9(9):3413–3417PubMedGoogle Scholar
  49. 49.
    Tao M, Shields p, Nie J, Millen A, Ambrosone C, Edge S, et al. (2009) DNA hypermethylation and clinicopathological features in breast cancer: the Western New York exposures and breast cancer (WEB) study. Breast Cancer Res Treat 114(3):559–568Google Scholar
  50. 50.
    Shinozaki M, Hoon DSB, Giuliano AE, Hansen NM, Wang H-J, Turner R et al (2005) Distinct hypermethylation profile of primary breast cancer is associated with sentinel lymph node metastasis. Clin Cancer Res 11(6):2156–2162CrossRefPubMedGoogle Scholar
  51. 51.
    Li S, Rong M, Iacopetta B (2006) DNA hypermethylation in breast cancer and its association with clinicopathological features. Cancer Lett 237(2):272–280CrossRefPubMedGoogle Scholar
  52. 52.
    Lehmann U, Langer F, Feist H, Glockner S, Hasemeier B, Kreipe H (2002) Quantitative assessment of promoter hypermethylation during breast cancer development. Am J Pathol 160(2):605–612PubMedGoogle Scholar
  53. 53.
    Dulaimi E, Hillinck J, de Caceres II, Al-Saleem T, Cairns P (2004) Tumor suppressor gene promoter hypermethylation in serum of breast cancer patients. Clin Cancer Res 10(18):6189–6193CrossRefPubMedGoogle Scholar
  54. 54.
    Jeronimo C, Monteiro P, Henrique R, Dinis-Ribeiro M, Costa I, Costa V et al (2008) Quantitative hypermethylation of a small panel of genes augments the diagnostic accuracy in fine-needle aspirate washings of breast lesions. Breast Cancer Res Treat 109(1):27–34CrossRefPubMedGoogle Scholar
  55. 55.
    Miltenburg DM, Speights VO Jr (2008) Benign breast disease. Obstet Gynecol Clin North Am 35(2):285–300CrossRefPubMedGoogle Scholar
  56. 56.
    Courtillot C, Plu-Bureau G, Binart N, Balleyguier C, Sigal-Zafrani B, Goffin V et al (2005) Benign breast diseases. J Mammary Gland Biol Neoplasia 10(4):325–335CrossRefPubMedGoogle Scholar
  57. 57.
    Di Vinci A, Perdelli L, Banelli B, Salvi S, Casciano I, Gelvi I et al (2005) p16 (INK4a) promoter methylation and protein expression in breast fibroadenoma and carcinoma. Int J Cancer 114(3):414–421CrossRefPubMedGoogle Scholar
  58. 58.
    Lewis CM, Cler LR, Bu D-W, Zochbauer-Muller S, Milchgrub S, Naftalis EZ et al (2005) Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk. Clin Cancer Res 11(1):166–172PubMedGoogle Scholar
  59. 59.
    Pu RT, Laitala LE, Alli PM, Fackler MJ, Sukumar S, Clark DP (2003) Methylation profiling of benign and malignant breast lesions and its application to cytopathology. Mod Pathol 16(11):1095–1101CrossRefPubMedGoogle Scholar
  60. 60.
    Cowin P, Rowlands TM, Hatsell SJ (2005) Cadherins and catenins in breast cancer. Curr Opin Cell Biol 17(5):499–508CrossRefPubMedGoogle Scholar
  61. 61.
    Euhus DM, Bu D, Milchgrub S, Xie X-J, Bian A, Leitch AM et al (2008) DNA methylation in benign breast epithelium in relation to age and breast cancer risk. Cancer Epidemiol Biomarkers Prev 17(5):1051–1059CrossRefPubMedGoogle Scholar
  62. 62.
    Singletary S, Patel-Parekh L, Bland K (2005) Treatment trends in early-stage invasive lobular carcinoma: a report from the National Cancer Data Base. Ann Surg 242:281–289CrossRefPubMedGoogle Scholar
  63. 63.
    Hanby AM, Hughes TA (2008) In situ and invasive lobular neoplasia of the breast. Histopathology 52(1):58–66PubMedGoogle Scholar
  64. 64.
    Cornford E, Wilson A, Athanassiou E, Galea M, Ellis I, Elston C et al (1995) Mammographic features of invasive lobular and invasive ductal carcinoma of the breast: a comparative analysis. Br J Radiol 68(809):450–453CrossRefPubMedGoogle Scholar
  65. 65.
    Bae YK, Brown A, Garrett E, Bornman D, Fackler MJ, Sukumar S et al (2004) Hypermethylation in histologically distinct classes of breast cancer. Clin Cancer Res 10(18):5998–6005CrossRefPubMedGoogle Scholar
  66. 66.
    Hoque MO, Feng Q, Toure P, Dem A, Critchlow CW, Hawes SE, et al. (2006) Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer. J Clin Oncol 24(26):4262–4269Google Scholar
  67. 67.
    Müller HM, Widschwendter A, Fiegl H, Ivarsson L, Goebel G, Perkmann E et al (2003) DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res 63(22):7641–7645PubMedGoogle Scholar
  68. 68.
    Papadopoulou E, Davilas E, Sotiriou V, Georgakopoulos E, Georgakopoulou S, Koliopanos A et al (2006) Cell-free DNA and RNA in plasma as a new molecular marker for prostate and breast cancer. Ann NY Acad Sci 1075(1):235–243CrossRefPubMedGoogle Scholar
  69. 69.
    Tan S-H, Ida H, Lau Q-C, Goh B-C, Chieng W-S, Loh M et al (2007) Detection of promoter hypermethylation in serum samples of cancer patients by methylation-specific polymerase chain reaction for tumour suppressor genes including RUNX3. Oncol Rep 18(5):1225–1230PubMedGoogle Scholar
  70. 70.
    Sharma G, Mirza S, Prasad CP, Srivastava A, Gupta SD, Ralhan R (2007) Promoter hypermethylation of p16INK4A, p14ARF, CyclinD2 and Slit2 in serum and tumor DNA from breast cancer patients. Life Sci 80(20):1873–1881CrossRefPubMedGoogle Scholar
  71. 71.
    Mirza S, Sharma G, Prasad CP, Parshad R, Srivastava A, Gupta SD et al (2007) Promoter hypermethylation of TMS1, BRCA1, ER[alpha] and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients. Life Sci 81(4):280–287CrossRefPubMedGoogle Scholar
  72. 72.
    Shukla S, Mirza S, Sharma G, Parshad R, Gupta SD, Ralhan R (2006) Detection of RASSF1A and RARbeta hypermethylation in serum DNA from breast cancer patients. Epigenetics 1(2):88–93PubMedCrossRefGoogle Scholar
  73. 73.
    Hu X-C, Wong I, Chow L (2003) Tumor-derived aberrant methylation in plasma of invasive ductal breast cancer patients: clinical implications. Oncology Rep 10:1811–1815Google Scholar
  74. 74.
    Pepe MS (2005) Evaluating technologies for classification and prediction in medicine. Stat Med 24(24):3687–3696CrossRefPubMedGoogle Scholar
  75. 75.
    Baker SG, Kramer BS, McIntosh M, Patterson BH, Shyr Y, Skates S (2006) Evaluating markers for the early detection of cancer: overview of study designs and methods. Clin Trials 3(1):43–56CrossRefPubMedGoogle Scholar
  76. 76.
    Vasilatos SN, Broadwater G, Barry WT, Baker JC Jr, Lem S, Dietze EC et al (2009) CpG Island tumor suppressor promoter methylation in non-BRCA-associated early mammary carcinogenesis. Cancer Epidemiol Biomarkers Prev 18(3):901–914CrossRefPubMedGoogle Scholar
  77. 77.
    Cottrell SE, Laird PW (2003) Sensitive detection of DNA methylation. Ann NY Acad Sci 983(1):120–130CrossRefPubMedGoogle Scholar
  78. 78.
    Ogino S, Kawasaki T, Brahmandam M, Cantor M, Kirkner GJ, Spiegelman D et al (2006) Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis. J Mol Diagn 8(2):209–217CrossRefPubMedGoogle Scholar
  79. 79.
    Esteller M, Corn P, Urena J, Gabrielson E, Baylin S, Herman J (1998) Inactivation of glutathione S-transferase P1 gene by promoter hypermethylation in human neoplasia. Cancer Res 58:4515–4518PubMedGoogle Scholar
  80. 80.
    Snell C, Krypuy M, Wong E, kConFab Investigators, Loughrey M, Dobrovic A (2008) BRCA1 promoter methylation in peripheral blood DNA of mutation negative familial breast cancer patients with a BRCA1 tumour phenotype. Breast Cancer Res 10(1):R12Google Scholar
  81. 81.
    Widschwendter M, Apostolidou S, Raum E, Rothenbacher D, Fiegl H, Menon U et al (2008) Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. PLoS ONE 3(7):e2656CrossRefPubMedGoogle Scholar
  82. 82.
    Sunami E, Vu A-T, Nguyen SL, Hoon DSB (2009) Analysis of methylated circulating DNA in cancer patients’ blood. DNA Methylation p. 349–356Google Scholar
  83. 83.
    Kagan J, Srivastava S, Barker PE, Belinsky SA, Cairns P (2007) Towards clinical application of methylated DNA sequences as cancer biomarkers: a joint NCI’s EDRN and NIST workshop on standards, methods, assays, reagents and tools. Cancer Res 67(10):4545–4549CrossRefPubMedGoogle Scholar
  84. 84.
    Cairns P (2007) Gene methylation and early detection of genitourinary cancer: the road ahead. Nat Rev Cancer 7(7):531–543CrossRefPubMedGoogle Scholar
  85. 85.
    Greendale GA, Palla SL, Ursin G, Laughlin GA, Crandall C, Pike MC et al (2005) 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 162(9):826–834CrossRefPubMedGoogle Scholar
  86. 86.
    Widschwendter M, Siegmund KD, Muller HM, Fiegl H, Marth C, Muller-Holzner E et al (2004) Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifen. Cancer Res 64(11):3807–3813CrossRefPubMedGoogle Scholar
  87. 87.
    Orlando F, Brown K (2009) Unraveling breast cancer heterogeneity through transcriptomic and epigenomic analysis. Ann Surg Oncol; Epub ahead of printGoogle Scholar
  88. 88.
    Locke I, Kote-Jarai Z, Jo Fackler M, Bancroft E, Osin p, Nerurkar A et al (2007) Gene promoter hypermethylation in ductal lavage fluid from healthy BRCA gene mutation carriers and mutation-negative controls. Breast Cancer Res 9(1):R20CrossRefPubMedGoogle Scholar
  89. 89.
    Butcher LM, Beck S (2008) Future impact of integrated high-throughput methylome analyses on human health and disease. J Genet Genomics 35(7):391–401CrossRefPubMedGoogle Scholar
  90. 90.
    Laird PW (2003) The power and the promise of DNA methylation markers. Nat Rev 3:253–266CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Jennifer Brooks
    • 1
    • 3
  • Paul Cairns
    • 2
  • Anne Zeleniuch-Jacquotte
    • 1
  1. 1.Division of Epidemiology, Department of Environmental MedicineNew York University School of MedicineNew YorkUSA
  2. 2.Department of Surgical OncologyFox Case Cancer CenterPhiladelphiaUSA
  3. 3.New YorkUSA

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