Clinical Oncology
Volume 19, Issue 6 , Pages 470-480 , August 2007

The Genomics Revolution and Radiotherapy

  • C.M.L. West

      Affiliations

    • Academic Radiation Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, UK
    • Corresponding Author InformationAuthor for correspondence: C. M. L. West, Academic Radiation Oncology, University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK. Tel: +44 161 446 8275.
    • ,
  • R.M. Elliott

      Affiliations

    • Academic Radiation Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, UK
    • ,
  • N.G. Burnet

      Affiliations

    • Academic Radiation Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, UK
    • University of Cambridge, Department of Oncology, Oncology Centre, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK

Received 9 February 2007 ,Accepted 28 February 2007.

References 

  1. Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921
  2. Collins FS, Green ED, Guttmacher AE, et al. A vision for the future of genomics research. Nature. 2003;422:835–847
  3. Collins FS. Finishing the euchromatic sequence of the human genome. Nature. 2004;431:931–945
  4. Burnet NG, Wurm R, Nyman J, et al. Normal tissue radiosensitivity—how important is it?. Clin Oncol (R Coll Radiol). 1996;8:25–34
  5. Mackay RI, Hendry JH. The modelled benefits of individualizing radiotherapy patients' dose using cellular radiosensitivity assays with inherent variability. Radiother Oncol. 1999;50:67–75
  6. Burnet NG, Nyman J, Turesson I, et al. The relationship between cellular radiation sensitivity and tissue response may provide the basis for individualising radiotherapy schedules. Radiother Oncol. 1994;33:228–238
  7. West CM, Davidson SE, Elyan SA, et al. Lymphocyte radiosensitivity is a significant prognostic factor for morbidity in carcinoma of the cervix. Int J Radiat Oncol Biol Phys. 2001;51:10–15
  8. Appleby JM, Barber JB, Levine E, et al. Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy. Br J Cancer. 1997;76:1546–1549
  9. Ramsay J, Birrell G, Lavin M. Testing for mutations of the ataxia telangiectasia gene in radiosensitive breast cancer patients. Radiother Oncol. 1998;47:125–128
  10. Clarke RA, Goozee GR, Birrell G, et al. Absence of ATM truncations in patients with severe acute radiation reactions. Int J Radiat Oncol Biol Phys. 1998;41:1021–1027
  11. Hall EJ, Schiff PB, Hanks GE, et al. A preliminary report: frequency of A-T heterozygotes among prostate cancer patients with severe late responses to radiation therapy. Cancer J Sci Am. 1998;4:385–389
  12. Shayeghi M, Seal S, Regan J, et al. Heterozygosity for mutations in the ataxia telangiectasia gene is not a major cause of radiotherapy complications in breast cancer patients. Br J Cancer. 1998;78:922–927
  13. Oppitz U, Bernthaler U, Schindler D, et al. Sequence analysis of the ATM gene in 20 patients with RTOG grade 3 or 4 acute and/or late tissue radiation side effects. Int J Radiat Oncol Biol Phys. 1999;44:981–988
  14. Iannuzzi CM, Atencio DP, Green S, et al. ATM mutations in female breast cancer patients predict for an increase in radiation-induced late effects. Int J Radiat Oncol Biol Phys. 2002;52:606–613
  15. Bremer M, Klopper K, Yamini P, et al. Clinical radiosensitivity in breast cancer patients carrying pathogenic ATM gene mutations: no observation of increased radiation-induced acute or late effects. Radiother Oncol. 2003;69:155–160
  16. Meyer A, John E, Dork T, et al. Breast cancer in female carriers of ATM gene alterations: outcome of adjuvant radiotherapy. Radiother Oncol. 2004;72:319–323
  17. Cesaretti JA, Stock RG, Lehrer S, et al. ATM sequence variants are predictive of adverse radiotherapy response among patients treated for prostate cancer. Int J Radiat Oncol Biol Phys. 2005;61:196–202
  18. Andreassen CN, Overgaard J, Alsner J, et al. ATM sequence variants and risk of radiation-induced subcutaneous fibrosis after postmastectomy radiotherapy. Int J Radiat Oncol Biol Phys. 2006;64:776–783
  19. Roberts SA, Spreadborough AR, Bulman B, et al. Heritability of cellular radiosensitivity: a marker of low-penetrance predisposition genes in breast cancer?. Am J Hum Genet. 1999;65:784–794
  20. Brem R, Cox DG, Chapot B, et al. The XRCC1 -77T->C variant: haplotypes, breast cancer risk, response to radiotherapy and the cellular response to DNA damage. Carcinogenesis. 2006;27:2469–2474
  21. Tan XL, Popanda O, Ambrosone CB, et al. Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients. Breast Cancer Res Treat. 2006;97:255–262
  22. Popanda O, Tan XL, Ambrosone CB, et al. Genetic polymorphisms in the DNA double-strand break repair genes XRCC3, XRCC2, and NBS1 are not associated with acute side effects of radiotherapy in breast cancer patients. Cancer Epidemiol Biomarkers Prev. 2006;15:1048–1050
  23. De Ruyck K, Van Eijkeren M, Claes K, et al. TGFbeta1 polymorphisms and late clinical radiosensitivity in patients treated for gynecologic tumors. Int J Radiat Oncol Biol Phys. 2006;65:1240–1248
  24. Damaraju S, Murray D, Dufour J, et al. Association of DNA repair and steroid metabolism gene polymorphisms with clinical late toxicity in patients treated with conformal radiotherapy for prostate cancer. Clin Cancer Res. 2006;12:2545–2554
  25. Andreassen CN, Alsner J, Overgaard M, et al. Risk of radiation-induced subcutaneous fibrosis in relation to single nucleotide polymorphisms in TGFB1, SOD2, XRCC1, XRCC3, APEX and ATM—a study based on DNA from formalin fixed paraffin embedded tissue samples. Int J Radiat Biol. 2006;82:577–586
  26. Kornguth DG, Garden AS, Zheng Y, et al. Gastrostomy in oropharyngeal cancer patients with ERCC4 (XPF) germline variants. Int J Radiat Oncol Biol Phys. 2005;62:665–671
  27. Chang-Claude J, Popanda O, Tan XL, et al. Association between polymorphisms in the DNA repair genes, XRCC1, APE1, and XPD and acute side effects of radiotherapy in breast cancer patients. Clin Cancer Res. 2005;11:4802–4809
  28. Andreassen CN, Alsner J, Overgaard J, et al. TGFB1 polymorphisms are associated with risk of late normal tissue complications in the breast after radiotherapy for early breast cancer. Radiother Oncol. 2005;75:18–21
  29. De Ruyck K, Van Eijkeren M, Claes K, et al. Radiation-induced damage to normal tissues after radiotherapy in patients treated for gynecologic tumors: association with single nucleotide polymorphisms in XRCC1, XRCC3, and OGG1 genes and in vitro chromosomal radiosensitivity in lymphocytes. Int J Radiat Oncol Biol Phys. 2005;62:1140–1149
  30. Moullan N, Cox DG, Angele S, et al. Polymorphisms in the DNA repair gene XRCC1, breast cancer risk, and response to radiotherapy. Cancer Epidemiol Biomarkers Prev. 2003;12:1168–1174
  31. Quarmby S, Fakhoury H, Levine E, et al. Association of transforming growth factor beta-1 single nucleotide polymorphisms with radiation-induced damage to normal tissues in breast cancer patients. Int J Radiat Biol. 2003;79:137–143
  32. Andreassen CN, Alsner J, Overgaard M, et al. Prediction of normal tissue radiosensitivity from polymorphisms in candidate genes. Radiother Oncol. 2003;69:127–135
  33. Angele S, Romestaing P, Moullan N, et al. ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity. Cancer Res. 2003;63:8717–8725
  34. Green H, Ross G, Peacock J, et al. Variation in the manganese superoxide dismutase gene (SOD2) is not a major cause of radiotherapy complications in breast cancer patients. Radiother Oncol. 2002;63:213–216
  35. Severin DM, Leong T, Cassidy B, et al. Novel DNA sequence variants in the hHR21 DNA repair gene in radiosensitive cancer patients. Int J Radiat Oncol Biol Phys. 2001;50:1323–1331
  36. Carlson CS, Eberle MA, Kruglyak L, et al. Mapping complex disease loci in whole-genome association studies. Nature. 2004;429:446–452
  37. Baumann M, Holscher T, Begg AC. Towards genetic prediction of radiation responses: ESTRO's GENEPI project. Radiother Oncol. 2003;69:121–125
  38. Burnet NG, Elliott RM, Dunning A, et al. Radiosensitivity, radiogenomics and RAPPER. Clin Oncol (R Coll Radiol). 2006;18:525–528
  39. West CM, McKay MJ, Holscher T, et al. Molecular markers predicting radiotherapy response: report and recommendations from an International Atomic Energy Agency technical meeting. Int J Radiat Oncol Biol Phys. 2005;62:1264–1273
  40. Iwakawa M, Imai T, Harada Y, et al. RadGenomics project. Nippon Igaku Hoshasen Gakkai Zasshi. 2002;62:484–489
  41. Iwakawa M, Noda S, Yamada S, et al. Analysis of non-genetic risk factors for adverse skin reactions to radiotherapy among 284 breast cancer patients. Breast Cancer. 2006;13:300–307
  42. Ho AY, Atencio DP, Peters S, et al. Genetic predictors of adverse radiotherapy effects: the Gene-PARE project. Int J Radiat Oncol Biol Phys. 2006;65:646–655
  43. Su D, Ma S, Liu P, et al. Genetic polymorphisms and treatment response in advanced non-small cell lung cancer. Lung Cancer (in press).
  44. Yoon SM, Hong YC, Park HJ, et al. The polymorphism and haplotypes of XRCC1 and survival of non-small-cell lung cancer after radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63:885–891
  45. Wu X, Gu J, Wu TT, et al. Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer. J Clin Oncol. 2006;24:3789–3798
  46. Saffari B, Bernstein L, Hong DC, et al. Association of p53 mutations and a codon 72 single nucleotide polymorphism with lower overall survival and responsiveness to adjuvant radiotherapy in endometrioid endometrial carcinomas. Int J Gynecol Cancer. 2005;15:952–963
  47. Li D, Frazier M, Evans DB, et al. Single nucleotide polymorphisms of RecQ1, RAD54L, and ATM genes are associated with reduced survival of pancreatic cancer. J Clin Oncol. 2006;24:1720–1728
  48. Li D, Liu H, Jiao L, et al. Significant effect of homologous recombination DNA repair gene polymorphisms on pancreatic cancer survival. Cancer Res. 2006;66:3323–3330
  49. Carles J, Monzo M, Amat M, et al. Single-nucleotide polymorphisms in base excision repair, nucleotide excision repair, and double strand break genes as markers for response to radiotherapy in patients with Stage I to II head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2006;66:1022–1030
  50. Sakano S, Wada T, Matsumoto H, et al. Single nucleotide polymorphisms in DNA repair genes might be prognostic factors in muscle-invasive bladder cancer patients treated with chemoradiotherapy. Br J Cancer. 2006;95:561–570
  51. Zhang W, Park DJ, Lu B, et al. Epidermal growth factor receptor gene polymorphisms predict pelvic recurrence in patients with rectal cancer treated with chemoradiation. Clin Cancer Res. 2005;11:600–605
  52. The International HapMap C. A haplotype map of the human genome. Nature. 2005;437:1299–1320
  53. Takabatake T, Fujikawa K, Tanaka S, et al. Array-CGH analyses of murine malignant lymphomas: genomic clues to understanding the effects of chronic exposure to low-dose-rate gamma rays on lymphomagenesis. Radiat Res. 2006;166:61–72
  54. Schena M, Shalon D, Davis RW, et al. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. 1995;270:467–470
  55. Hardiman G. Microarray platforms—comparisons and contrasts. Pharmacogenomics. 2004;5:487–502
  56. Amundson SA, Fornace AJ. Monitoring human radiation exposure by gene expression profiling: possibilities and pitfalls. Health Phys. 2003;85:36–42
  57. Park WY, Hwang CI, Im CN, et al. Identification of radiation-specific responses from gene expression profile. Oncogene. 2002;21:8521–8528
  58. Wang HP, Long XH, Sun ZZ, et al. Identification of differentially transcribed genes in human lymphoblastoid cells irradiated with 0.5 Gy of gamma-ray and the involvement of low dose radiation inducible CHD6 gene in cell proliferation and radiosensitivity. Int J Radiat Biol. 2006;82:181–190
  59. Dai JM, Sun DC, Lin RX, et al. Microarray analysis of differentially expressed genes in mouse bone marrow tissues after ionizing radiation. Int J Radiat Biol. 2006;82:511–521
  60. Kis E, Szatmari T, Keszei M, et al. Microarray analysis of radiation response genes in primary human fibroblasts. Int J Radiat Oncol Biol Phys. 2006;66:1506–1514
  61. Christiansen H, Batusic D, Saile B, et al. Identification of genes responsive to gamma radiation in rat hepatocytes and rat liver by cDNA array gene expression analysis. Radiat Res. 2006;165:318–325
  62. Rodningen OK, Overgaard J, Alsner J, et al. Microarray analysis of the transcriptional response to single or multiple doses of ionizing radiation in human subcutaneous fibroblasts. Radiother Oncol. 2005;77:231–240
  63. Kruse JJ, te Poele JA, Velds A, et al. Identification of differentially expressed genes in mouse kidney after irradiation using microarray analysis. Radiat Res. 2004;161:28–38
  64. Kruse JJ, te Poele JA, Russell NS, et al. Microarray analysis to identify molecular mechanisms of radiation-induced microvascular damage in normal tissues. Int J Radiat Oncol Biol Phys. 2004;58:420–426
  65. Vozenin-Brotons MC, Milliat F, Linard C, et al. Gene expression profile in human late radiation enteritis obtained by high-density cDNA array hybridization. Radiat Res. 2004;161:299–311
  66. Amundson SA, Grace MB, McLeland CB, et al. Human in vivo radiation-induced biomarkers: gene expression changes in radiotherapy patients. Cancer Res. 2004;64:6368–6371
  67. Jen KY, Cheung VG. Transcriptional response of lymphoblastoid cells to ionizing radiation. Genome Res. 2003;13:2092–2100
  68. Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA. 2001;98:5116–5121
  69. Ford BN, Wilkinson D, Thorleifson EM, et al. Gene expression responses in lymphoblastoid cells after radiation exposure. Radiat Res. 2001;156:668–671
  70. Snyder AR, Morgan WF. Gene expression profiling after irradiation: clues to understanding acute and persistent responses?. Cancer Metastasis Rev. 2004;23:259–268
  71. Gasch AP, Huang M, Metzner S, et al. Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p. Mol Biol Cell. 2001;12:2987–3003
  72. Fry RC, DeMott MS, Cosgrove JP, et al. The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA. BMC Genomics. 2006;7:313
  73. Bourgier C, Haydont V, Milliat F, et al. Inhibition of Rho kinase modulates radiation induced fibrogenic phenotype in intestinal smooth muscle cells through alteration of the cytoskeleton and connective tissue growth factor expression. Gut. 2005;54:336–343
  74. Guisasola MC, Calvo F, Marcos P, et al. Peripheral leukocyte response to oncological radiotherapy: expression of heat shock proteins. Int J Radiat Biol. 2006;82:171–179
  75. Kote-Jarai Z, Matthews L, Osorio A, et al. Accurate prediction of BRCA1 and BRCA2 heterozygous genotype using expression profiling after induced DNA damage. Clin Cancer Res. 2006;12:3896–3901
  76. Kote-Jarai Z, Williams RD, Cattini N, et al. Gene expression profiling after radiation-induced DNA damage is strongly predictive of BRCA1 mutation carrier status. Clin Cancer Res. 2004;10:958–963
  77. Quarmby S, West C, Magee B, et al. Differential expression of cytokine genes in fibroblasts derived from skin biopsies of patients who developed minimal or severe normal tissue damage after radiotherapy. Radiat Res. 2002;157:243–248
  78. Hummerich J, Werle-Schneider G, Popanda O, et al. Constitutive mRNA expression of DNA repair-related genes as a biomarker for clinical radio-resistance: a pilot study in prostate cancer patients receiving radiotherapy. Int J Radiat Biol. 2006;82:593–604
  79. van de Vijver MJ, He YD, van't Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009
  80. Ein-Dor L, Kela I, Getz G, et al. Outcome signature genes in breast cancer: is there a unique set?. Bioinformatics. 2005;21:171–178
  81. Shen R, Ghosh D, Chinnaiyan AM. Prognostic meta-signature of breast cancer developed by two-stage mixture modeling of microarray data. BMC Genomics. 2004;5:94
  82. Kitahara O, Katagiri T, Tsunoda T, et al. Classification of sensitivity or resistance of cervical cancers to ionizing radiation according to expression profiles of 62 genes selected by cDNA microarray analysis. Neoplasia. 2002;4:295–303
  83. Wong YF, Selvanayagam ZE, Wei N, et al. Expression genomics of cervical cancer: molecular classification and prediction of radiotherapy response by DNA microarray. Clin Cancer Res. 2003;9:5486–5492
  84. Harima Y, Togashi A, Horikoshi K, et al. Prediction of outcome of advanced cervical cancer to thermoradiotherapy according to expression profiles of 35 genes selected by cDNA microarray analysis. Int J Radiat Oncol Biol Phys. 2004;60:237–248
  85. Otomo T, Hishii M, Arai H, et al. Microarray analysis of temporal gene responses to ionizing radiation in two glioblastoma cell lines: up-regulation of DNA repair genes. J Radiat Res (Tokyo). 2004;45:53–60
  86. Tewari D, Monk BJ, Al-Ghazi MS, et al. Gene expression profiling of in vitro radiation resistance in cervical carcinoma: a feasibility study. Gynecol Oncol. 2005;99:84–91
  87. Torres-Roca JF, Eschrich S, Zhao H, et al. Prediction of radiation sensitivity using a gene expression classifier. Cancer Res. 2005;65:7169–7176
  88. Giri U, Ashorn CL, Ramdas L, et al. Molecular signatures associated with clinical outcome in patients with high-risk head-and-neck squamous cell carcinoma treated by surgery and radiation. Int J Radiat Oncol Biol Phys. 2006;64:670–677
  89. Winter SC, Buffa FM, Silva P, et al. Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers. Cancer Res. 2007;67(7):in press
  90. Alaiya A, Al-Mohanna M, Linder S. Clinical cancer proteomics: promises and pitfalls. J Proteome Res. 2005;4:1213–1222
  91. Sreekumar A, Nyati MK, Varambally S, et al. Profiling of cancer cells using protein microarrays: discovery of novel radiation-regulated proteins. Cancer Res. 2001;61:7585–7593
  92. Allal AS, Kahne T, Reverdin AK, et al. Radioresistance-related proteins in rectal cancer. Proteomics. 2004;4:2261–2269
  93. Anscher MS, Kong FM, Jirtle RL. The relevance of transforming growth factor beta 1 in pulmonary injury after radiation therapy. Lung Cancer. 1998;19:109–120
  94. Anscher MS, Kong FM, Marks LB, et al. Changes in plasma transforming growth factor beta during radiotherapy and the risk of symptomatic radiation-induced pneumonitis. Int J Radiat Oncol Biol Phys. 1997;37:253–258
  95. Chen HW, Chang YC, Lai YL, et al. Change of plasma transforming growth factor-beta1 levels in nasopharyngeal carcinoma patients treated with concurrent chemo-radiotherapy. Jpn J Clin Oncol. 2005;35:427–432
  96. Li C, Wilson PB, Levine E, et al. TGF-beta1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis. Int J Cancer. 1999;84:155–159
  97. Evans ES, Kocak Z, Zhou SM, et al. Does transforming growth factor-beta1 predict for radiation-induced pneumonitis in patients treated for lung cancer?. Cytokine. 2006;35:186–192
  98. Dickson J, Davidson SE, Hunter RD, et al. Pretreatment plasma TGF beta 1 levels are prognostic for survival but not morbidity following radiation therapy of carcinoma of the cervix. Int J Radiat Oncol Biol Phys. 2000;48:991–995
  99. Loncaster JA, Harris AL, Davidson SE, et al. Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. Cancer Res. 2001;61:6394–6399
  100. Wilson CR, Davidson SE, Margison GP, et al. Expression of Ku70 correlates with survival in carcinoma of the cervix. Br J Cancer. 2000;83:1702–1706
  101. Buffa FM, Bentzen SM, Daley FM, et al. Molecular marker profiles predict locoregional control of head and neck squamous cell carcinoma in a randomized trial of continuous hyperfractionated accelerated radiotherapy. Clin Cancer Res. 2004;10:3745–3754
  102. Eriksen JG, Buffa FM, Alsner J, et al. Molecular profiles as predictive marker for the effect of overall treatment time of radiotherapy in supraglottic larynx squamous cell carcinomas. Radiother Oncol. 2004;72:275–282
  103. Freier K, Pungs S, Sticht C, et al. High survivin expression is associated with favorable outcome in advanced primary oral squamous cell carcinoma after radiation therapy. Int J Cancer. 2007;120:942–946

PII: S0936-6555(07)00536-5

doi: 10.1016/j.clon.2007.02.016

Clinical Oncology
Volume 19, Issue 6 , Pages 470-480 , August 2007

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