Seminars in Radiation Oncology
Volume 18, Issue 2 , Pages 126-135 , April 2008

Genetic Markers for Prediction of Normal Tissue Toxicity After Radiotherapy

References 

  1. Andreassen CN, Alsner J, Overgaard J. Does variability in normal tissue reactions after radiotherapy have a genetic basis—Where and how to look for it?. Radiother Oncol. 2002;64:131–140
  2. Fernet M, Hall J. Genetic biomarkers of therapeutic radiation sensitivity. DNA Repair (Amst). 2004;3:1237–1243
  3. Andreassen CN. Can risk of radiotherapy-induced normal tissue complications be predicted from genetic profiles?. Acta Oncol. 2005;44:801–815
  4. West CM, Elliott RM, Burnet NG. The genomics revolution and radiotherapy. Clin Oncol (R Coll Radiol). 2007;19:470–480
  5. Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921
  6. Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science. 2001;291:1304–1351
  7. International HapMap Consortium. A haplotype map of the human genome. Nature. 2005;437:1299–1320
  8. Liu H, Prugnolle F, Manica A, et al. A geographically explicit genetic model of worldwide human-settlement history. Am J Hum Genet. 2006;79:230–237
  9. Manica A, Amos W, Balloux F, et al. The effect of ancient population bottlenecks on human phenotypic variation. Nature. 2007;448:346–348
  10. Hirschhorn JN, Daly MJ. Genome-wide association studies for common diseases and complex traits. Nat Rev Genet. 2005;6:95–108
  11. Li J, Zhou Y, Elston RC. Haplotype-based quantitative trait mapping using a clustering algorithm. BMC Bioinformatics. 2006;7:258
  12. Satagopan JM, Verbel DA, Venkatraman ES, et al. Two-stage designs for gene-disease association studies. Biometrics. 2002;58:163–170
  13. Easton DF, Pooley KA, Dunning AM, et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature. 2007;447:1087–1093
  14. Cox A, Dunning AM, Garcia-Closas M, et al. A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet. 2007;39:352–358
  15. The Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661–678
  16. Parkes M, Barrett JC, Prescott NJ, et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet. 2007;39:830–832
  17. Todd JA, Walker NM, Cooper JD, et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet. 2007;39:857–864
  18. Zeggini E, Weedon MN, Lindgren CM, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007;316:1336–1341
  19. Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316:889–894
  20. Saxena R, Voight BF, Lyssenko V, et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science. 2007;316:1331–1336
  21. Chanock SJ, Manolio T, Boehnke M, et al. Replicating genotype-phenotype associations. Nature. 2007;447:655–660
  22. Marchini J, Howie B, Myers S, et al. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet. 2007;39:906–913
  23. ENCODE Project Consortium. The ENCODE (ENCyclopedia Of DNA Elements) Project. Science. 2004;306:636–640
  24. ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447:799–816
  25. Rogers PB, Plowman PN, Harris SJ, et al. Four radiation hypersensitivity cases and their implications for clinical radiotherapy. Radiother Oncol. 2000;57:143–154
  26. Bentzen SM, Overgaard M. Relationship between early and late normal-tissue injury after postmastectomy radiotherapy. Radiother Oncol. 1991;20:159–165
  27. Bentzen SM, Overgaard M, Overgaard J. Clinical correlations between late normal tissue endpoints after radiotherapy: implications for predictive assays of radiosensitivity. Eur J Cancer. 1993;29A:1373–1376
  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. Andreassen CN, Alsner J, Overgaard M, et al. Prediction of normal tissue radiosensitivity from polymorphisms in candidate genes. Radiother Oncol. 2003;69:127–135
  30. Hölscher T, Bentzen SM, Baumann M. Influence of connective tissue diseases on the expression of radiation side effects: A systematic review. Radiother Oncol. 2006;78:123–130
  31. Overgaard M, Bentzen SM, Christensen JJ, et al. The value of the NSD formula in equation of acute and late radiation complications in normal tissue following 2 and 5 fractions per week in breast cancer patients treated with postmastectomy irradiation. Radiother Oncol. 1987;9:1–11
  32. Bentzen SM, Overgaard M, Thames HD, et al. Early and late normal-tissue injury after postmastectomy radiotherapy alone or combined with chemotherapy. Int J Radiat Biol. 1989;56:711–715
  33. 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
  34. Cesaretti JA, Stock RG, Atencio DP, et al. A genetically determined dose-volume histogram predicts for rectal bleeding among patients treated with prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2007;68:1410-1406
  35. 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
  36. Syrris P, Carter ND, Metcalfe JC, et al. Transforming growth factor-beta1 gene polymorphisms and coronary artery disease. Clin Sci (Lond). 1998;95:659–667
  37. Awad MR, El-Gamel A, Hasleton P, et al. Genotypic variation in the transforming growth factor-beta1 gene: Association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation. 1998;66:1014–1020
  38. Grainger DJ, Heathcote K, Chiano M, et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet. 1999;8:93–97
  39. Hinke V, Seck T, Clanget C, et al. Association of transforming growth factor-beta1 (TGFbeta1) T29 –> C gene polymorphism with bone mineral density (BMD), changes in BMD, and serum concentrations of TGF-beta1 in a population-based sample of postmenopausal german women. Calcif Tissue Int. 2001;69:315–320
  40. Grainger DJ, Metcalfe JC. Tamoxifen: teaching an old drug new tricks?. Nat Med. 1996;2:381–385
  41. Hoffmann SC, Stanley EM, Cox ED, et al. Ethnicity greatly influences cytokine gene polymorphism distribution. Am J Transplant. 2002;2:560–567
  42. Bentzen SM, Thames HD, Overgaard M. Latent-time estimation for late cutaneous and subcutaneous radiation reactions in a single-follow-up clinical study. Radiother Oncol. 1989;15:267–274
  43. Jung H, Beck-Bornholdt HP, Svoboda V, et al. Quantification of late complications after radiation therapy. Radiother Oncol. 2001;61:233–246
  44. 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
  45. Iwakawa M, Imai T, Harada Y, et al. RadGenomics project. Nippon Igaku Hoshasen Gakkai Zasshi. 2002;62:484–489
  46. Burnet NG, Elliott RM, Dunning A, et al. Radiosensitivity, radiogenomics and RAPPER. Clin Oncol (R Coll Radiol). 2006;18:525–528
  47. GENEPI Homepage. www.genepi-estro.orgAccessed December 13, 2007
  48. Strauch K, Fimmers R, Baur MP, et al. How to model a complex trait (1. General considerations and suggestions). Hum Hered. 2003;55:202–210
  49. Pan WH, Lynn KS, Chen CH, et al. Using endophenotypes for pathway clusters to map complex disease genes. Genet Epidemiol. 2006;30:143–154
  50. Johansen J, Bentzen SM, Overgaard J, et al. Relationship between the in vitro radiosensitivity of skin fibroblasts and the expression of subcutaneous fibrosis, telangiectasia, and skin erythema after radiotherapy. Radiother Oncol. 1996;40:101–109
  51. 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
  52. Borgmann K, Roper B, El-Awady R, et al. Indicators of late normal tissue response after radiotherapy for head and neck cancer: Fibroblasts, lymphocytes, genetics (DNA repair, and chromosome aberrations). Radiother Oncol. 2002;64:141–152
  53. Hoeller U, Borgmann K, Bonacker M, et al. Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer. Radiother Oncol. 2003;69:137–144
  54. Rieger KE, Hong WJ, Tusher VG, et al. Toxicity from radiation therapy associated with abnormal transcriptional responses to DNA damage. Proc Natl Acad Sci U S A. 2004;101:6635–6640
  55. Svensson JP, Stalpers LJ, Esveldt-van Lange RE, et al. Analysis of gene expression using gene sets discriminates cancer patients with and without late radiation toxicity. PLoS Med. 2006;3:e422
  56. Rødningen OK, Børresen-Dale AL, Alsner J, et al: Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis. Radiother Oncol (in press)
  57. Alsner J, Rødningen OK, Overgaard J. Differential gene expression before and after ionizing radiation of subcutaneous fibroblasts identifies breast cancer patients resistant to radiation-induced fibrosis. Radiother Oncol. 2007;83:261–266
  58. Herskind C, Bentzen SM, Overgaard J, et al. Differentiation state of skin fibroblast cultures versus risk of subcutaneous fibrosis after radiotherapy. Radiother Oncol. 1998;47:263–269
  59. Herskind C, Johansen J, Bentzen SM, et al. Fibroblast differentiation in subcutaneous fibrosis after postmastectomy radiotherapy. Acta Oncol. 2000;39:383–388
  60. Travis EL. Genetic susceptibility to late normal tissue injury. Semin Radiat Oncol. 2007;17:149–155
  61. Kruse JJ, Stewart FA. Gene expression arrays as a tool to unravel mechanisms of normal tissue radiation injury and prediction of response. World J Gastroenterol. 2007;13:2669–2674
  62. Ahn J, Ambrosone CB, Kanetsky PA, et al. Polymorphisms in genes related to oxidative stress (CAT. MnSOD, MPO, and eNOS) and acute toxicities from radiation therapy following lumpectomy for breast cancer. Clin Cancer Res. 2006;12:7063–7070
  63. Ambrosone CB, Tian C, Ahn J, et al. Genetic predictors of acute toxicities related to radiation therapy following lumpectomy for breast cancer: A case-series study. Breast Cancer Res. 2006;8:R40
  64. 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
  65. 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
  66. 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
  67. 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
  68. 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
  69. 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
  70. Clarke RA, Goozee GR, Birrell GW, et al. Absence of ATM truncations in patients with severe acute radiation reactions. Int J Radiat Oncol Biol Phys. 1998;41:1021–1027
  71. 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
  72. 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
  73. De Ruyck K, Wilding CS, Van Eijkeren M, et al. Microsatellite polymorphisms in DNA repair genes XRCC1. XRCC3 and XRCC5 in patients with gynecological tumors: Association with late clinical radiosensitivity and cancer incidence. Radiat Res. 2005;164:237–244
  74. 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
  75. Edvardsen H, Kristensen VN, Grenaker Alnaes GI, et al. Germline glutathione S-transferase variants in breast cancer: Relation to diagnosis and cutaneous long-term adverse effects after two fractionation patterns of radiotherapy. Int J Radiat Oncol Biol Phys. 2007;67:1163–1171
  76. Gaffney DK, Brohet RM, Lewis CM, et al. Response to radiation therapy and prognosis in breast cancer patients with BRCA1 and BRCA2 mutations. Radiother Oncol. 1998;47:129–136
  77. Giotopoulos G, Symonds RP, Foweraker K, et al. The late radiotherapy normal tissue injury phenotypes of telangiectasia, fibrosis and atrophy in breast cancer patients have distinct genotype-dependent causes. Br J Cancer. 2007;96:1001–1007
  78. 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
  79. 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
  80. Ho AY, Fan G, Atencio DP, et al. Possession of ATM sequence variants as predictor for late normal tissue responses in breast cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2007;69:677–684
  81. 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
  82. 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
  83. Leong T, Whitty J, Keilar M, et al. Mutation analysis of BRCA1 and BRCA2 cancer predisposition genes in radiation hypersensitive cancer patients. Int J Radiat Oncol Biol Phys. 2000;48:959–965
  84. 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
  85. 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
  86. Pierce LJ, Strawderman M, Narod SA, et al. Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol. 2000;18:3360–3369
  87. 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
  88. Price EA, Bourne SL, Radbourne R, et al. Rare microsatellite polymorphisms in the DNA repair genes XRCC1. XRCC3 and XRCC5 associated with cancer in patients of varying radiosensitivity. Somat Cell Mol Genet. 1997;23:237–247
  89. 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
  90. 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
  91. 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
  92. 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
  93. 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
  94. Weissberg JB, Huang DD, Swift M. Radiosensitivity of normal tissues in ataxia-telangiectasia heterozygotes. Int J Radiat Oncol Biol Phys. 1998;42:1133–1136

PII: S1053-4296(07)00095-1

doi: 10.1016/j.semradonc.2007.10.004

Seminars in Radiation Oncology
Volume 18, Issue 2 , Pages 126-135 , April 2008

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