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Studying Cancer Evolution in Barrett’s Esophagus and Esophageal Adenocarcinoma

  • Thomas G. PaulsonEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 908)

Abstract

Technological advances in genome sequencing and copy number analysis have allowed researchers to catalog the wide variety of genomic alterations that occur across diverse cancer types. For most cancer types, the lack of high-frequency alterations and the heterogeneity observed both within and between tumors suggest neoplastic progression proceeds through a branched evolutionary pathway as proposed by Nowell in 1976, as opposed to the linear pathway that has dominated medical science for the last century. To understand how cancer evolves over time and space in the body, new study designs are needed that can distinguish between alterations that develop in patients who progress to cancer from to those who don’t. Here we present approaches developed in the study of Barrett’s esophagus, a premalignant precursor of esophageal adenocarcinoma, and discuss strategies for applying the results from these analyses to address the critical clinical problems of overdiagnosis of benign disease, early detection of life-threatening cancer, and effective risk stratification.

Keywords

Barrett’s esophagus Esophageal adenocarcinoma Cancer evolution Branched evolution Cancer risk stratification 

References

  1. 1.
    Nowell PC. The clonal evolution of tumor cell populations. Science. 1976;194(4260):23–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977;74(12):5463–7.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Aktipis CA, Kwan VS, Johnson KA, et al. Overlooking evolution: a systematic analysis of cancer relapse and therapeutic resistance research. PLoS One. 2011;6(11):e26100. doi: 10.1371/journal.pone.0026100.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Croswell JM, Ransohoff DF, Kramer BS. Principles of cancer screening: lessons from history and study design issues. Semin Oncol. 2010;37(3):202–15. doi: 10.1053/j.seminoncol.2010.05.006.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319(9):525–32.PubMedCrossRefGoogle Scholar
  6. 6.
    Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes. Science. 2013;339(6127):1546–58. doi: 10.1126/science.1235122.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921. doi: 10.1038/35057062.PubMedCrossRefGoogle Scholar
  8. 8.
    Dulbecco R. A turning point in cancer research: sequencing the human genome. Science. 1986;231(4742):1055–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Leiserson MD, Vandin F, Wu HT, et al. Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes. Nat Genet. 2015;47(2):106–14. doi: 10.1038/ng.3168.PubMedCrossRefGoogle Scholar
  10. 10.
    Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366(10):883–92. doi: 10.1056/NEJMoa1113205.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    de Bruin EC, McGranahan N, Mitter R, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science. 2014;346(6206):251–6. doi: 10.1126/science.1253462.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Zhang J, Fujimoto J, Zhang J, et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science. 2014;346(6206):256–9. doi: 10.1126/science.1256930.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Sottoriva A, Kang H, Ma Z, et al. A Big Bang model of human colorectal tumor growth. Nat Genet. 2015;47(3):209–16. doi: 10.1038/ng.3214.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Navin N, Kendall J, Troge J, et al. Tumour evolution inferred by single-cell sequencing. Nature. 2011;472(7341):90–4. doi: 10.1038/nature09807.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Murugaesu N, Wilson GA, Birkbak NJ, et al. Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy. Cancer Discov. 2015. doi: 10.1158/2159-8290.CD-15-0412.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Li X, Galipeau PC, Paulson TG, et al. Temporal and spatial evolution of somatic chromosomal alterations: a case-cohort study of Barrett’s esophagus. Cancer Prev Res (Phila). 2014;7(1):114–27. doi: 10.1158/1940-6207.CAPR-13-0289.CrossRefGoogle Scholar
  17. 17.
    Agrawal N, Jiao Y, Bettegowda C, et al. Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma. Cancer Discov. 2012;2(10):899–905. doi: 10.1158/2159-8290.CD-12-0189.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Dulak AM, Stojanov P, Peng S, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013;45(5):478–86. doi: 10.1038/ng.2591.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Nones K, Waddell N, Wayte N, et al. Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun. 2014;5:5224. doi: 10.1038/ncomms6224.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Streppel MM, Lata S, DelaBastide M, et al. Next-generation sequencing of endoscopic biopsies identifies ARID1A as a tumor-suppressor gene in Barrett’s esophagus. Oncogene. 2014;33(3):347–57. doi: 10.1038/onc.2012.586.PubMedCrossRefGoogle Scholar
  21. 21.
    Weaver JM, Ross-Innes CS, Shannon N, et al. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat Genet. 2014;46(8):837–43. doi: 10.1038/ng.3013.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21. doi: 10.1038/nature12477.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9. doi: 10.1038/nature13480.CrossRefGoogle Scholar
  24. 24.
    Wang K, Yuen ST, Xu J, et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014;46(6):573–82. doi: 10.1038/ng.2983.PubMedCrossRefGoogle Scholar
  25. 25.
    Wang Y, Waters J, Leung ML, et al. Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature. 2014;512(7513):155–60. doi: 10.1038/nature13600.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Paulson TG, Reid BJ. Focus on Barrett’s esophagus and esophageal adenocarcinoma. Cancer Cell. 2004;6(1):11–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Reid BJ, Li X, Galipeau PC, et al. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer. 2010;10(2):87–101. doi: 10.1038/nrc2773.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Wang KK, Sampliner RE. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett’s esophagus. Am J Gastroenterol. 2008;103(3):788–97.PubMedCrossRefGoogle Scholar
  29. 29.
    Howlader N, Noone AM, Krapcho M, et al. (2014). SEER cancer statistics review, 1975-2011. from National Cancer Institute http://seer.cancer.gov/csr/1975_2011/.
  30. 30.
    Ostrowski J, Mikula M, Karczmarski J, et al. Molecular defense mechanisms of Barrett’s metaplasia estimated by an integrative genomics. J Mol Med. 2007;85(7):733–43.PubMedCrossRefGoogle Scholar
  31. 31.
    Dixon J, Strugala V, Griffin SM, et al. Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett’s esophagus. Am J Gastroenterol. 2001;96(9):2575–83.PubMedCrossRefGoogle Scholar
  32. 32.
    Tobey NA, Argote CM, Kav T, et al. Anion transport in human squamous and Barrett’s esophageal epithelium. Gastroenterology. 2005;128:A234.Google Scholar
  33. 33.
    Jovov B, Van Itallie CM, Shaheen NJ, et al. Claudin-18: a dominant tight junction protein in Barrett’s esophagus and likely contributor to its acid resistance. Am J Physiol Gastrointest Liver Physiol. 2007;293(6):G1106–13.PubMedCrossRefGoogle Scholar
  34. 34.
    Leedham SJ, Preston SL, McDonald SA, et al. Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett’s oesophagus. Gut. 2008;57(8):1041–8.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    McDonald SA, Lavery D, Wright NA, et al. Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol. 2015;12(1):50–60. doi: 10.1038/nrgastro.2014.181.PubMedCrossRefGoogle Scholar
  36. 36.
    Wang X, Ouyang H, Yamamoto Y, et al. Residual embryonic cells as precursors of a Barrett’s-like metaplasia. Cell. 2011;145(7):1023–35. doi: 10.1016/j.cell.2011.05.026.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Xian W, Ho KY, Crum CP, et al. Cellular origin of Barrett’s esophagus: controversy and therapeutic implications. Gastroenterology. 2012;142(7):1424–30. doi: 10.1053/j.gastro.2012.04.028.PubMedCrossRefGoogle Scholar
  38. 38.
    Vaughan TL, Fitzgerald RC. Precision prevention of oesophageal adenocarcinoma. Nat Rev Gastroenterol Hepatol. 2015;12(4):243–8. doi: 10.1038/nrgastro.2015.24.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Bhat S, Coleman HG, Yousef F, et al. Risk of malignant progression in Barrett’s esophagus patients: results from a large population-based study. J Natl Cancer Inst. 2011;103(13):1049–57. doi: 10.1093/jnci/djr203.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    de Jonge PJ, van Blankenstein M, Looman CW, et al. Risk of malignant progression in patients with Barrett’s oesophagus: a Dutch nationwide cohort study. Gut. 2010;59(8):1030–6. doi: 10.1136/gut.2009.176701.PubMedCrossRefGoogle Scholar
  41. 41.
    Hvid-Jensen F, Pedersen L, Drewes AM, et al. Incidence of adenocarcinoma among patients with Barrett’s esophagus. N Engl J Med. 2011;365(15):1375–83. doi: 10.1056/NEJMoa1103042.PubMedCrossRefGoogle Scholar
  42. 42.
    Welch HG, Black WC. Overdiagnosis in cancer. J Natl Cancer Inst. 2010;102(9):605–13. doi: 10.1093/jnci/djq099.PubMedCrossRefGoogle Scholar
  43. 43.
    Levine DS, Blount PL, Rudolph RE, et al. Safety of a systematic endoscopic biopsy protocol in patients with Barrett’s esophagus. Am J Gastroenterol. 2000;95(5):1152–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Varghese S, Lao-Sirieix P, Fitzgerald RC. Identification and clinical implementation of biomarkers for Barrett’s esophagus. Gastroenterology. 2012;142(3):435–41. doi: 10.1053/j.gastro.2012.01.013. e432.PubMedCrossRefGoogle Scholar
  45. 45.
    Carter SL, Cibulskis K, Helman E, et al. Absolute quantification of somatic DNA alterations in human cancer. Nat Biotechnol. 2012;30(5):413–21. doi: 10.1038/nbt.2203.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Rabinovitch PS, Reid BJ, Haggitt RC, et al. Progression to cancer in Barrett’s esophagus is associated with genomic instability. Lab Invest. 1988;60(1):65–71.Google Scholar
  47. 47.
    Barrett MT, Sanchez CA, Prevo LJ, et al. Evolution of neoplastic cell lineages in Barrett oesophagus. Nat Gen. 1999;22(1):106–9.CrossRefGoogle Scholar
  48. 48.
    Blount PL, Meltzer SJ, Yin J, et al. Clonal ordering of 17p and 5q allelic losses in Barrett dysplasia and adenocarcinoma. Proc Natl Acad Sci U S A. 1993;90(8):3221–5.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Neshat K, Sanchez CA, Galipeau PC, et al. Barrett’s esophagus: a model of human neoplastic progression. Cold Spring Harb Symp Quant Biol. 1994;59:577–83.PubMedCrossRefGoogle Scholar
  50. 50.
    Maley CC, Galipeau PC, Finley JC, et al. Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet. 2006;38(4):468–73.PubMedCrossRefGoogle Scholar
  51. 51.
    Galipeau PC, Li X, Blount PL, et al. NSAIDs modulate CDKN2A, TP53, and DNA content risk for future esophageal adenocarcinoma. PLoS Med. 2007;4:e67.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Kostadinov RL, Kuhner MK, Li X, et al. NSAIDs modulate clonal evolution in Barrett’s esophagus. PLoS Genet. 2013;9(6):e1003553. doi: 10.1371/journal.pgen.1003553.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012;481(7381):306–13. doi: 10.1038/nature10762.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Lagergren J, Bergstrom R, Lindgren A, et al. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999;340(11):825–31.PubMedCrossRefGoogle Scholar
  55. 55.
    Whiteman DC, Sadeghi S, Pandeya N, et al. Combined effects of obesity, acid reflux and smoking on the risk of adenocarcinomas of the oesophagus. Gut. 2008;57(2):173–80.PubMedCrossRefGoogle Scholar
  56. 56.
    Wu AH, Tseng CC, Bernstein L. Hiatal hernia, reflux symptoms, body size, and risk of esophageal and gastric adenocarcinoma. Cancer. 2003;98(5):940–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Anderson AR, Weaver AM, Cummings PT, et al. Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment. Cell. 2006;127(5):905–15. doi: 10.1016/j.cell.2006.09.042.PubMedCrossRefGoogle Scholar
  58. 58.
    Jenkins GJ, Cronin J, Alhamdani A, et al. The bile acid deoxycholic acid has a non-linear dose response for DNA damage and possibly NF-kappaB activation in oesophageal cells, with a mechanism of action involving ROS. Mutagenesis. 2008;23(5):399–405.PubMedCrossRefGoogle Scholar
  59. 59.
    Grisham MB, Jourd’heuil D, Wink DA. Review article: chronic inflammation and reactive oxygen and nitrogen metabolism--implications in DNA damage and mutagenesis. Aliment Pharmacol Ther. 2000;14 Suppl 1:3–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Sihvo EI, Ruohtula T, Auvinen MI, et al. Simultaneous progression of oxidative stress and angiogenesis in malignant transformation of Barrett esophagus. J Thorac Cardiovasc Surg. 2003;126(6):1952–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Foster JM, Oumie A, Togneri FS, et al. Cross-laboratory validation of the OncoScan(R) FFPE assay, a multiplex tool for whole genome tumour profiling. BMC Med Genomics. 2015;8(1):5. doi: 10.1186/s12920-015-0079-z.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Prentice RL. A case-cohort design for epidemiologic cohort studies and disease prevention trials. Biometrika. 1986;73:1–11.CrossRefGoogle Scholar
  63. 63.
    Cheng H, Bjerknes M, Amar J. Methods for the determination of epithelial cell kinetic parameters of human colonic epithelium isolated from surgical and biopsy specimens. Gastroenterology. 1984;86(1):78–85.PubMedGoogle Scholar
  64. 64.
    Yatabe Y, Tavare S, Shibata D. Investigating stem cells in human colon by using methylation patterns. Proc Natl Acad Sci U S A. 2001;98(19):10839–44.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Beroukhim R, Mermel CH, Porter D, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010;463(7283):899–905. doi: 10.1038/nature08822.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Li X, Galipeau PC, Sanchez CA, et al. Single nucleotide polymorphism-based genome-wide chromosome copy change, loss of heterozygosity, and aneuploidy in Barrett’s esophagus neoplastic progression. Cancer Prev Res (Phila). 2008;1(6):413–23. doi: 10.1158/1940-6207.CAPR-08-0121.CrossRefGoogle Scholar
  67. 67.
    Fleming TR, Powers JH. Biomarkers and surrogate endpoints in clinical trials. Stat Med. 2012;31(25):2973–84. doi: 10.1002/sim.5403.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Prentice RL. Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med. 1989;8(4):431–40.PubMedCrossRefGoogle Scholar
  69. 69.
    Montgomery E, Bronner MP, Goldblum JR, et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol. 2001;32(4):368–78.PubMedCrossRefGoogle Scholar
  70. 70.
    Odze RD. What the gastroenterologist needs to know about the histology of Barrett’s esophagus. Curr Opin Gastroenterol. 2011;27(4):389–96. doi: 10.1097/MOG.0b013e328346f551.PubMedCrossRefGoogle Scholar
  71. 71.
    Reid BJ, Haggitt RC, Rubin CE, et al. Observer variation in the diagnosis of dysplasia in Barrett’s esophagus. Hum Pathol. 1988;19(2):166–78.PubMedCrossRefGoogle Scholar
  72. 72.
    Reid BJ, Levine DS, Longton G, et al. Predictors of progression to cancer in Barrett’s esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets. Am J Gastroenterol. 2000;95(7):1669–76.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Schnell TG, Sontag SJ, Chejfec G, et al. Long-term nonsurgical management of Barrett’s esophagus with high-grade dysplasia. Gastroenterology. 2001;120(7):1607–19.PubMedCrossRefGoogle Scholar
  74. 74.
    Sharma P, Falk GW, Weston AP, et al. Dysplasia and cancer in a large multicenter cohort of patients with Barrett’s esophagus. Clin Gastroenterol Hepatol. 2006;4(5):566–72.PubMedCrossRefGoogle Scholar
  75. 75.
    Weston AP, Sharma P, Topalovski M, et al. Long-term follow-up of Barrett’s high-grade dysplasia. Am J Gastroenterol. 2000;95(8):1888–93.PubMedCrossRefGoogle Scholar
  76. 76.
    Orlando RC. Mucosal defense in Barrett’s esophagus. In S R, Sharma P, editors. Barrett’s esophagus and esophageal adenocarcinoma. 2nd ed. Oxford, UK: Blackwell Publishing, Ltd.; 2006. p. 60–72.Google Scholar
  77. 77.
    Bandla S, Pennathur A, Luketich JD, et al. Comparative genomics of esophageal adenocarcinoma and squamous cell carcinoma. Ann Thorac Surg. 2012;93(4):1101–6. doi: 10.1016/j.athoracsur.2012.01.064.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Gu J, Ajani JA, Hawk ET, et al. Genome-wide catalogue of chromosomal aberrations in barrett’s esophagus and esophageal adenocarcinoma: a high-density single nucleotide polymorphism array analysis. Cancer Prev Res (Phila). 2010;3(9):1176–86. doi: 10.1158/1940-6207.CAPR-09-0265.CrossRefGoogle Scholar
  79. 79.
    Nancarrow DJ, Handoko HY, Smithers BM, et al. Genome-wide copy number analysis in esophageal adenocarcinoma using high-density single-nucleotide polymorphism arrays. Cancer Res. 2008;68(11):4163–72.PubMedCrossRefGoogle Scholar
  80. 80.
    Maley CC, Galipeau PC, Li X, et al. Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett’s esophagus. Cancer Res. 2004;64(10):3414–27.PubMedCrossRefGoogle Scholar
  81. 81.
    Stephens PJ, Greenman CD, Fu B, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011;144(1):27–40. doi: 10.1016/j.cell.2010.11.055.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Li X, Paulson TG, Galipeau PC, et al. Assessment of esophageal adenocarcinoma risk using somatic chromosome alterations in longitudinal samples in Barrett’s esophagus. Cancer Prev Res (Phila). 2015. doi: 10.1158/1940-6207.capr-15-0130.Google Scholar
  83. 83.
    Kandoth C, McLellan MD, Vandin F, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9. doi: 10.1038/nature12634.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Levine DS, Haggitt RC, Blount PL, et al. An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus. Gastroenterology. 1993;105(1):40–50.PubMedCrossRefGoogle Scholar
  85. 85.
    Kadri SR, Lao-Sirieix P, O’Donovan M, et al. Acceptability and accuracy of a non-endoscopic screening test for Barrett’s oesophagus in primary care: cohort study. BMJ. 2010;341:c4372. doi: 10.1136/bmj.c4372.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Ross-Innes CS, Debiram-Beecham I, O’Donovan M, et al. Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett's esophagus: a multi-center case-control study. PLoS Med. 2015;12(1):e1001780. doi: 10.1371/journal.pmed.1001780.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Bridson EY, Gould GW. Quantal microbiology. Lett Appl Microbiol. 2000;30(2):95–8.PubMedCrossRefGoogle Scholar
  88. 88.
    Buks E, Schuster R, Heiblum M, et al. Dephasing in electron interference by a “which-path” detector. Nature. 1998;391(6670):871–4.CrossRefGoogle Scholar
  89. 89.
    Rothwell PM, Fowkes FG, Belch JF, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377(9759):31–41. doi: 10.1016/S0140-6736(10)62110-1.PubMedCrossRefGoogle Scholar
  90. 90.
    Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345(6274):458–60.PubMedCrossRefGoogle Scholar
  91. 91.
    Baca SC, Prandi D, Lawrence MS, et al. Punctuated evolution of prostate cancer genomes. Cell. 2013;153(3):666–77. doi: 10.1016/j.cell.2013.03.021.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Wang KK. Current Strategies in the management of Barrett’s esophagus. Curr Gastroenterol Rep. 2005;7(3):196–201.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Farrow DC, Vaughan TL, Sweeney C, et al. Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer. Cancer Causes Control. 2000;11(3):231–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Mueller KL. Cancer immunology and immunotherapy. Realizing the promise. Introduction. Science. 2015;348(6230):54–5. doi: 10.1126/science.348.6230.54.PubMedCrossRefGoogle Scholar
  95. 95.
    Flajnik MF, Kasahara M. Origin and evolution of the adaptive immune system: genetic events and selective pressures. Nat Rev Genet. 2010;11(1):47–59. doi: 10.1038/nrg2703.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Seattle Barrett’s Esophagus ProgramFred Hutchinson Cancer Research CenterSeattleUSA

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