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Potential screening assays for individual radiation sensitivity and susceptibility and their current validation state

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Pages 280-296 | Received 18 Apr 2019, Accepted 03 Jun 2019, Published online: 26 Jul 2019

References

  • Abend M, Badie C, Quintens R, Kriehuber R, Manning G, Macaeva E, Njima M, Oskamp D, Strunz S, Moertl S, et al. 2016. Examining radiation-induced in vivo and in vitro gene expression changes of the peripheral blood in different laboratories for biodosimetry purposes: first RENEB gene expression study. Radiat Res. 185:109–123.
  • Ainsbury E, Bouffler S, Dörr W, Graw J, Muirhead C, Edwards A, Cooper J. 2009. Radiation cataractogenesis: a review of recent studies. Radiat Res. 172:1–9.
  • Andreassen CN, Rosenstein BS, Kerns SL, Ostrer H, De Ruysscher D, Cesaretti JA, Barnett GC, Dunning AM, Dorling L, West CML, et al., International Radiogenomics Consortium (RgC). 2016a. Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients. Radiother Oncol. 121:431–439.
  • Andreassen C, Schack L, Laursen L, Alsner J. 2016b. Radiogenomics - current status, challenges and future directions. Cancer Lett. 382:127–136.
  • Anglesio MS, Papadopoulos N, Ayhan A, Nazeran TM, Noë M, Horlings HM, Lum A, Jones S, Senz J, Seckin T, et al. 2017. Cancer-associated mutations in endometriosis without cancer. N Engl J Med. 376:1835–1848.
  • Azimzadeh O, Azizova T, Merl-Pham J, Subramanian V, Bakshi MV, Moseeva M, Zubkova O, Hauck SM, Anastasov N, Atkinson MJ, et al. 2017. A dose-dependent perturbation in cardiac energy metabolism is linked to radiation-induced ischemic heart disease in Mayak nuclear workers. Oncotarget. 8:9067–9078.
  • Azria D, Belkacemi Y, Romieu G, Gourgou S, Gutowski M, Zaman K, Moscardo C, Lemanski C, Coelho M, Rosenstein B, et al. 2010. Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial. Lancet Oncol. 11:258–265.
  • Azria D, Ozsahin M, Kramar A, Peters S, Atencio DP, Crompton N, Mornex F, Pèlegrin A, Dubois J-B, Mirimanoff R-O, et al. 2008. Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy. Clin Cancer Res. 14:6284–6288.
  • Azria D, Riou O, Castan F, Nguyen T, Peignaux K, Lemanski C, Lagrange J-L, Kirova Y, Lartigau E, Belkacemi Y, et al. 2015. Radiation-induced CD8 T-lymphocyte apoptosis as a predictor of breast fibrosis after radiotherapy: results of the prospective Multicenter French Trial. EBioMedicine. 2:1965–1973.
  • Badie C, Goodhardt M, Waugh A, Doyen N, Foray N, Calsou P, Singleton B, Gell D, Salles B, Jeggo P, et al. 1997. A DNA double-strand break defective fibroblast cell line (180BR) derived from a radiosensitive patient represents a new mutant phenotype. Cancer Res. 57:4600–4607.
  • Badie C, Iliakis G, Foray N, Alsbeih G, Pantellias G, Okayasu R, Cheong N, Russell N, Begg A, Arlett C. 1995. Defective repair of DNA double-strand breaks and chromosome damage in fibroblasts from a radiosensitive leukemia patient. Cancer Res. 55:1232–1234.
  • Badie C, Kabacik S, Balagurunathan Y, Bernard N, Brengues M, Faggioni G, Greither R, Lista F, Peinnequin A, Poyot T, et al. 2013. Laboratory intercomparison of gene expression assays. Radiat Res. 181:138–148.
  • Baijer J, Déchamps N, Perdry H, Morales P, Kerns S, Vasilescu A, Baulande S, Azria D, Roméo P, Schmitz A. 2016. TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis. Oncotarget. 7:21416–21427.
  • Bakhmutsky MV, Joiner MC, Jones TB, Tucker JD. 2014. Differences in cytogenetic sensitivity to ionizing radiation in newborns and adults. Radiat Res. 181:605–616.
  • Baria K, Warren C, Roberts S, West C, Scott D. 2001. Chromosomal radiosensitivity as a marker of predisposition to common cancers? Br J Cancer. 84:892–896.
  • Barnett GC, Thompson D, Fachal L, Kerns S, Talbot C, Elliott RM, Dorling L, Coles CE, Dearnaley DP, Rosenstein BS, et al. 2014. A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity. Radiother Oncol. 111:178–185.
  • Behjati S, Gundem G, Wedge DC, Roberts ND, Tarpey PS, Cooke SL, Loo P, Alexandrov LB, Ramakrishna M, Davies H, et al. 2016. Mutational signatures of ionizing radiation in second malignancies. Nat Commun. 7:12605.
  • Beitsch PD, Whitworth PW, Hughes K, Patel R, Rosen B, Compagnoni G, Baron P, Simmons R, Smith LA, Grady I, et al. 2019. Underdiagnosis of hereditary breast cancer: are genetic testing guidelines a tool or an obstacle? J Clin Oncol. 37:453–460.
  • Benafif S, Kote-Jarai Z, Eeles RA, PRACTICAL Consortium. 2018. A review of prostate cancer genome-wide association studies (GWAS). Cancer Epidemiol Biomarkers Prev. 27:845–857.
  • Bentzen SM. 2006. Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer. 6:702–713.
  • Bernstein JL, Concannon P, WECARE Study Collaborative Group. 2017. ATM, radiation, and the risk of second primary breast cancer. Int J Radiat Biol. 93:1121–1127.
  • Best T, Li D, Skol AD, Kirchhoff T, Jackson SA, Yasui Y, Bhatia S, Strong LC, mchek S, Nathanson KL, et al. 2011. Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin’s lymphoma. Nat Med. 17:941–943.
  • Blankenberg S, Zeller T, Saarela O, Havulinna AS, Kee F, Tunstall-Pedoe H, Kuulasmaa K, Yarnell J, Schnabel RB, Wild PS, et al. 2010. Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project. Circulation. 121:2388–2397.
  • Bordón E, Henríquez-Hernández L, Lara P, Pinar B, Rodríguez-Gallego C, Lloret M. 2011. Role of CD4 and CD8 T-lymphocytes, B-lymphocytes and natural killer cells in the prediction of radiation-induced late toxicity in cervical cancer patients. Int J Radiat Biol. 87:424–431.
  • Bordón E, Henríquez-Hernández L, Lara PC, Ruíz A, Pinar B, Rodríguez-Gallego C, Lloret M. 2010. Prediction of clinical toxicity in locally advanced head and neck cancer patients by radio-induced apoptosis in peripheral blood lymphocytes (PBLs). Radiat Oncol. 5:4.
  • Bourguignon MH, Gisone PA, Perez MR, Michelin S, Dubner D, Giorgio M, Carosella ED. 2005. Genetic and epigenetic features in radiation sensitivity. Eur J Nucl Med Mol Imaging. 32:351–368.
  • Bourton EC, Plowman PN, Smith D, Arlett CF, Parris CN. 2011. Prolonged expression of the γH2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment. Int J Cancer. 129:2928–2934.
  • Brandmaier A, Hou S-Q, Demaria S, Formenti SC, Shen WH. 2017. PTEN at the interface of immune tolerance and tumor suppression. Front Biol. 12:163–174.
  • Brengues M, Lapierre A, Bourgier C, Pèlegrin A, Özsahin M, Azria D. 2017. T lymphocytes to predict radiation-induced late effects in normal tissues. Expert Rev Mol Diagn. 17:119–127.
  • Britel M, Bourguignon M, Foray N. 2018. The use of the term ‘radiosensitivity’ through history of radiation: from clarity to confusion. Int J Radiat Biol. 94:1–31.
  • Bruheim K, Guren MG, Skovlund E, Hjermstad MJ, Dahl O, Frykholm G, Carlsen E, Tveit K. 2010. Late side effects and quality of life after radiotherapy for rectal cancer. Int J Radiat Oncol Biology Phys. 76:1005–1011.
  • Brzozowska K, Pinkawa M, Eble MJ, Müller W-U, Wojcik A, Kriehuber R, Schmitz S. 2012. In vivo versus in vitro individual radiosensitivity analysed in healthy donors and in prostate cancer patients with and without severe side effects after radiotherapy. Int J Radiat Biol. 88:405–413.
  • Chen Y, Trotti A, Coleman NC, Machtay M, Mirimanoff RO, Hay J, O’Brien PC, El-Gueddari B, Salvajoli JV, Jeremic B. 2006. Adverse event reporting and developments in radiation biology after normal tissue injury: International Atomic Energy Agency consultation. Int J Radiat Oncol Biology Phys. 64:1442–1451.
  • Chin MS, Freniere BB, Lancerotto L, Lujan-Hernandez J, Saleeby JH, Lo Y-C, Orgill DP, Lalikos JF, Fitzgerald TJ. 2015. Hyperspectral imaging as an early biomarker for radiation exposure and microcirculatory damage. Front Oncol. 5:232.
  • Chin MS, Siegel-Reamer L, FitzGerald GA, Wyman A, Connor NM, Lo Y-C, Sioshansi S, Moni J, Cicchetti MG, Lalikos JF, et al. 2017. Association between cumulative radiation dose, adverse skin reactions, and changes in surface hemoglobin among women undergoing breast conserving therapy. Clin Transl Radiat Oncol. 4:15–23.
  • Constine LS, Ronckers CM, Hua C-H, Olch A, Kremer LCM, Jackson A, Bentzen SM. 2019. Pediatric Normal Tissue Effects in the Clinic (PENTEC): an international collaboration to analyse normal tissue radiation dose-volume response relationships for paediatric cancer patients. Clin Oncol (R Coll Radiol). 31:199–207.
  • Coombs CC, Zehir A, Devlin SM, Kishtagari A, Syed A, Jonsson P, Hyman DM, Solit DB, Robson ME, Baselga J, et al. 2017. Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and associated with adverse clinical outcomes. Cell Stem Cell. 21:374–382.e4.
  • Cosset J-M, Hetnal M, Chargari C. 2018. Second cancers after radiotherapy: update and recommandations. Radioprotection. 53:101–105.
  • Crompton NE, Ozsahin M. 1997. A versatile and rapid assay of radiosensitivity of peripheral blood leukocytes based on DNA and surface-marker assessment of cytotoxicity. Radiat Res. 147:55–60.
  • de Gonzalez A, Curtis RE, Kry SF, Gilbert E, Lamart S, Berg CD, Stovall M, Ron E. 2011. Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. Lancet Oncol. 12:353–360.
  • Desai P, Mencia-Trinchant N, Savenkov O, Simon MS, Cheang G, Lee S, Samuel M, Ritchie EK, Guzman ML, Ballman KV, et al. 2018. Somatic mutations precede acute myeloid leukemia years before diagnosis. Nat Med. 24:1015–1023.
  • Djuzenova CS, Elsner I, Katzer A, Worschech E, Distel LV, Flentje M, Polat B. 2013. Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci. Radiat Oncol. 8:98.
  • Djuzenova CS, Zimmermann M, Katzer A, Fiedler V, Distel LV, Gasser M, Waaga-Gasser A-M, Flentje M, Polat B. 2015. A prospective study on histone γ-H2AX and 53BP1 foci expression in rectal carcinoma patients: correlation with radiation therapy-induced outcome. BMC Cancer. 15:856.
  • Emanueli C, Shearn A, Angelini GD, Sahoo S. 2015. Exosomes and exosomal miRNAs in cardiovascular protection and repair. Vascul Pharmacol. 71:24–30.
  • European Commission High Level and Expert Group. 2009. EUR 23884—HLEG report on European Low Dose Risk Research Radiation Protection. Luxembourg: Office for Official Publications of the European Communities. Available at: https://cordis.europa.eu/docs/publications/1070/107087891-6_en.pdf.
  • Fachal L, Gómez-Caamaño A, Barnett GC, Peleteiro P, Carballo AM, Calvo-Crespo P, Kerns SL, Sánchez-García M, Lobato-Busto R, Dorling L, et al. 2014. A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1. Nat Genet. 46:891–894.
  • Ferlazzo ML, Bourguignon M, Foray N. 2017. Functional assays for individual radiosensitivity: a critical review. Semin Radiat Oncol. 27:310–315.
  • Fleckenstein J, Kühne M, Seegmüller K, Derschang S, Melchior P, Gräber S, Fricke A, Rübe CE, Rübe C. 2011. The impact of individual in vivo repair of DNA double-strand breaks on oral mucositis in adjuvant radiotherapy of head-and-neck cancer. Int J Radiat Oncol Biology Phys. 81:1465–1472.
  • Floyd DN, Cassoni AM. 1994. Intrinsic radiosensitivity of adult and cord blood lymphocytes as determined by the micronucleus assay. Eur J Cancer. 30:615–620.
  • Foray N, Bourguignon M, Hamada N. 2016. Individual response to ionizing radiation. Mutat Res. 770:369–386.
  • Foro P, Algara M, Lozano J, Rodriguez N, Sanz X, Torres E, Carles J, Reig A, Membrive I, Quera J, et al. 2014. Relationship between radiation-induced apoptosis of T lymphocytes and chronic toxicity in patients with prostate cancer treated by radiation therapy: a prospective study. Int J Radiat Oncol Biology Phys. 88:1057–1063.
  • Friedman DL, Kadan-Lottick NS, Whitton J, Mertens AC, Yasui Y, Liu Y, Meadows AT, Robison LL, Strong LC. 2005. Increased risk of cancer among siblings of long-term childhood cancer survivors: a report from the childhood cancer survivor study. Cancer Epidemiol Biomarkers Prev. 14:1922–1927.
  • Fucic A, Brunborg G, Lasan R, Jezek D, Knudsen LE, Merlo DF. 2008. Genomic damage in children accidentally exposed to ionizing radiation: a review of the literature. Mutat Res Rev Mutat Res. 658:111–123.
  • Fuentes-Raspall MJ, Caragol I, Alonso C, y Cajal T, Fisas D, Seoane A, Carvajal N, Bonache S, Díez O, Gutiérrez-Enríquez S. 2015. Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism. Apoptosis. 20:371–382.
  • Furutani E, Shimamura A. 2017. Germline genetic predisposition to hematologic malignancy. J Clin Oncol. 35:1018–1028.
  • Gomolka M, Oestreicher U, Rößler U, Samaga D, Endesfelder D, Lang P, Neumaier K, Belka C, Niemeyer M, Kiechle M, et al. 2018. Age-dependent differences in DNA damage after in vitro CT exposure. Int J Radiat Biol. 94:272–282.
  • Goutham H, Mumbrekar K, Vadhiraja B, Fernandes D, Sharan K, Parashiva G, Kapaettu S, Sadashiva S. 2012. DNA double-strand break analysis by γ-H2AX foci: a useful method for determining the overreactors to radiation-induced acute reactions among head-and-neck cancer patients. Int J Radiat Oncol Biology Phys. 84:e607–e612.
  • Granzotto A, Benadjaoud M, Vogin G, Devic C, Ferlazzo ML, Bodgi L, Pereira S, Sonzogni L, Forcheron F, Viau M, et al. 2016. Influence of nucleoshuttling of the ATM protein in the healthy tissues response to radiation therapy: toward a molecular classification of human radiosensitivity. Int J Radiat Oncol Biology Phys. 94:450–460.
  • Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, et al. 2013. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 15:565–574.
  • Greve B, Bölling T, Amler S, Rössler U, Gomolka M, Mayer C, Popanda O, Dreffke K, Rickinger A, Fritz E, et al. 2012. Evaluation of different biomarkers to predict individual radiosensitivity in an inter-laboratory comparison–lessons for future studies. PLoS One. 7:e47185.
  • Habash M, Bohorquez LC, Kyriakou E, Kron T, Martin OA, Blyth BJ. 2017. Clinical and functional assays of radiosensitivity and radiation-induced second cancer. Cancers. 9:147.
  • Hadj-Hamou N-S, Ugolin N, Ory C, Britzen-Laurent N, Sastre-Garau X, Chevillard S, Malfoy B. 2011. A transcriptome signature distinguished sporadic from postradiotherapy radiation-induced sarcomas. Carcinogenesis. 32:929–934.
  • Hall J, Jeggo PA, West C, Gomolka M, Quintens R, Badie C, Laurent O, Aerts A, Anastasov N, Azimzadeh O, et al. 2017. Ionizing radiation biomarkers in epidemiological studies – an update. Mutat Res Rev Mutat Res. 771:59–84.
  • Hamada N. 2017. Ionizing radiation sensitivity of the ocular lens and its dose rate dependence. Int J Radiat Biol. 93:1024–1034.
  • Health Protection Agency. 2013. Human radiosensitivity: a report of the independent advisory group on ionising radiation. Available at: https://assets.publishing.service.gov.uk/government/…/RCE-21_v2_for_website.pdf.
  • Hollstein M, Hupp T. 2011. Chek2ing out the p53 pathway: can Puma lead the way? Cell Cycle. 10:1524.
  • Hourigan CS, Savani BN. 2018. Leukaemia risk associated with low-dose radiation. Lancet Haematol. 5:e324–e325.
  • Hubenak JR, Zhang Q, Branch CD, Kronowitz SJ. 2014. Mechanisms of injury to normal tissue after radiotherapy: a review. Plast Reconstr Surg. 133:49e–56e.
  • ICRP. 2007. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 37:1–332.
  • Ioannidis JP, Bossuyt PM. 2017. Waste, leaks, and failures in the biomarker pipeline. Clin Chem. 63:963–972.
  • Ishihara S, Iinuma H, Fukushima Y, Akahane T, Horiuchi A, Shimada R, Shibuya H, Hayama T, Yamada H, Nozawa K, et al. 2012. Radiation-induced apoptosis of peripheral blood lymphocytes is correlated with histological regression of rectal cancer in response to preoperative chemoradiotherapy. Ann Surg Oncol. 19:1192–1198.
  • Jacob S. 2012. Ionizing radiation as a risk factor for cataract: what about low-dose effects? J Clin Exp Ophthalmol. S1:005.
  • Kabacik S, Manning G, Raffy C, Bouffler S, Badie C. 2015. Time, dose and ataxia telangiectasia mutated (ATM) status dependency of coding and noncoding RNA expression after ionizing radiation exposure. Radiat Res. 183:325–337.
  • Kabacik S, Ortega-Molina A, Efeyan A, Finnon P, Bouffler S, Serrano M, Badie C. 2011. A minimally invasive assay for individual assessment of the ATM/CHEK2/p53 pathway activity. Cell Cycle. 10:1152–1161.
  • Kan C, Zhang J. 2015. BRCA1 mutation: a predictive marker for radiation therapy? Int J Radiat Oncol Biol Phys. 93:281–293.
  • Kerns SL, Dorling L, Fachal L, Bentzen S, Pharoah PD, Barnes DR, Gómez-Caamaño A, Carballo AM, Dearnaley DP, Peleteiro P, et al., Radiogenomics Consortium. 2016. Meta-analysis of Genome Wide Association Studies identifies genetic markers of late toxicity following radiotherapy for prostate cancer. EBioMedicine. 10:150–163.
  • Kessler T, Vilne B, Schunkert H. 2016. The impact of genome-wide association studies on the pathophysiology and therapy of cardiovascular disease . Embo Mol Med. 8:688–701.
  • Kovacic S, Bakran M. 2012. Genetic susceptibility to atherosclerosis. Stroke Res Treat. 2012:362941.
  • Kreuzer M, Auvinen A, Cardis E, Durante M, Harms-Ringdahl M, Jourdain JR, Madas BG, Ottolenghi A, Pazzaglia S, Prise KM, et al. 2018. Multidisciplinary European Low Dose Initiative (MELODI): strategic research agenda for low dose radiation risk research. Radiat Environ Biophys. 57:5–15.
  • Kreuzer M, Auvinen A, Cardis E, Hall J, Jourdain J-R, Laurier D, Little MP, Peters A, Raj K, Russell NS, et al. 2015. Low-dose ionising radiation and cardiovascular diseases-Strategies for molecular epidemiological studies in Europe. Mutat Res Rev Mutat Res. 764:90–100.
  • Leng S, Picchi MA, Liu Y, Thomas CL, Willis DG, Bernauer AM, Carr TG, Mabel PT, Han Y, Amos CI, et al. 2013. Genetic variation in SIRT1 affects susceptibility of lung squamous cell carcinomas in former uranium miners from the Colorado plateau. Carcinogenesis. 34:1044–1050.
  • Leng S, Thomas CL, Snider AM, Picchi MA, Chen W, Willis DG, Carr TG, Krzeminski J, Desai D, Shantu A, et al. 2016. Radon exposure, IL-6 promoter variants, and lung squamous cell carcinoma in former uranium miners. Environ Health Persp. 124:445–451.
  • Li C, Athar M. 2016. Ionizing radiation exposure and basal cell carcinoma pathogenesis. Radiat Res. 186:217–228.
  • Li P, Du C, Xu W, Shi Z, Zhang Q, Li Z, Fu S. 2013. Correlation of dynamic changes in γ-H2AX expression in peripheral blood lymphocytes from head and neck cancer patients with radiation-induced oral mucositis. Radiat Oncol. 8:155.
  • Lobachevsky P, Leong T, Daly P, Smith J, Best N, Tomaszewski J, Thompson ER, Li N, Campbell IG, Martin RF, et al. 2016. Compromized DNA repair as a basis for identification of cancer radiotherapy patients with extreme radiosensitivity. Cancer Lett. 383:212–219.
  • Loh P-R, Genovese G, Handsaker RE, Finucane HK, Reshef YA, Palamara P, Birmann BM, Talkowski ME, Bakhoum SF, McCarroll SA, et al. 2018. Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Nature. 559:350–355.
  • Manning G, Kabacik S, Finnon P, Bouffler S, Badie C. 2013. High and low dose responses of transcriptional biomarkers in ex vivo X-irradiated human blood. Int J Radiat Biol. 89:512–522.
  • Marcu LG. 2017. Photons – radiobiological issues related to the risk of second malignancies. Phys Med. 42:213–220.
  • Meadows AT, Friedman DL, Neglia JP, Mertens AC, Donaldson SS, Stovall M, Hammond S, Yasui Y, Inskip PD. 2009. Second neoplasms in survivors of childhood cancer: findings from the childhood cancer survivor study cohort. J Clin Oncol. 27:2356–2362.
  • Mertens AC, Mitby PA, Radloff G, Jones IM, Perentesis J, Kiffmeyer WR, Neglia JP, Meadows A, Potter JD, Friedman D, et al. 2004. XRCC1 and glutathione-S-transferase gene polymorphisms and susceptibility to radiotherapy-related malignancies in survivors of Hodgkin disease. Cancer. 101:1463–1472.
  • Milano MT, Constine LS, Okunieff P. 2007. Normal tissue tolerance dose metrics for radiation therapy of major organs. Semin Radiat Oncol. 17:131–140.
  • Morton LM, Sampson JN, Armstrong GT, Chen TH, Hudson MM, Karlins E, Dagnall CL, Li SA, Wilson CL, Srivastava DK, et al. 2017. Genome-wide association study to identify susceptibility loci that modify radiation-related risk for breast cancer after childhood cancer. J Natl Cancer Inst. 109.
  • Mumbrekar K, Fernandes D, Goutham H, Sharan K, Vadhiraja B, Satyamoorthy K, Sadashiva S. 2014. Influence of double-strand break repair on radiation therapy-induced acute skin reactions in breast cancer patients. Int J Radiat Oncol Biol Phys. 88:671–676.
  • Neriishi K, Hayashi T, Nakashima E, Imai K, Nakachi K. 2009. ATM haplotypes and radiosensitivity in A-bomb survivors: preliminary trial using existing data at RERF. Abstract Book of Radiation Cataractogenesis Workshop. Hiroshima, Japan: RERF.
  • O'Brien G, Cruz-Garcia L, Majewski M, Grepl J, Abend M, Port M, Tichý A, Sirak I, Malkova A, Donovan E, et al. 2018. FDXR is a biomarker of radiation exposure in vivo. Sci Rep. 8:684.
  • Oestreicher U, Endesfelder D, Gomolka M, Kesminiene A, Lang P, Lindholm C, Rößler U, Samaga D, Kulka U. 2018. Automated scoring of dicentric chromosomes differentiates increased radiation sensitivity of young children after low dose CT exposure in vitro. Int J Radiat Biol. 94:1017–1026.
  • Olsson CE, Jackson A, Deasy JO, Thor M. 2018. A systematic post-QUANTEC review of tolerance doses for late toxicity after prostate cancer radiotherapy. Int J Radiat Oncol Biology Phys. 102:1514–1532.
  • Ordoñez R, Henríquez-Hernández LA, Federico M, Valenciano A, Pinar B, Lloret M, Bordón E, Rodríguez-Gallego C, Lara PC. 2014. Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients. Strahlenther Onkol. 190:210–216.
  • Ory C, Ugolin N, Levalois C, Lacroix L, Caillou B, Bidart J-M, Schlumberger M, Diallo I, de Vathaire F, Hofman P, et al. 2011. Gene expression signature discriminates sporadic from post-radiotherapy-induced thyroid tumors. Endocr Relat Cancer 18:193–206.
  • Ozsahin M, Crompton N, Gourgou S, Kramar A, Li L, Shi Y, Sozzi W, Zouhair A, Mirimanoff RO, Azria D. 2005. CD4 and CD8 T-lymphocyte apoptosis can predict radiation-induced late toxicity: a prospective study in 399 patients. Clin Cancer Res. 11:7426–7433.
  • Pereira S, Bodgi L, Duclos M, Canet A, Ferlazzo ML, Devic C, Granzotto A, Deneuve S, Vogin G, Foray N. 2018. Fast and binary assay for predicting radiosensitivity based on the theory of ATM nucleo-shuttling: development, validation, and performance. Int J Radiat Oncol Biology Phys. 100:353–360.
  • Pérez-Losada J, Castellanos-Martín A, Mao J-H. 2011. Cancer evolution and individual susceptibility. Integr Biol (Camb). 3:316–328.
  • Pointreau Y, Kreps S, Hennequin C. 2010. Évaluation des effets secondaires des radiations ionisantes. Cancer Radiothér. 14:246–249.
  • Rajaraman P, Hauptmann M, Bouffler S, Wojcik A. 2018. Human individual radiation sensitivity and prospects for prediction. Ann ICRP. 47:126–141.
  • Repussard J. 2017. Low dose effects research in Europe: eight years of evolution towards new paradigms. Radioprotection. 52:251–258.
  • Rosenberger A, Hung RJ, Christiani DC, Caporaso NE, Liu G, Bojesen SE, Le Marchand L, Haiman CA, Albanes D, Aldrich MC, et al. 2018. Genetic modifiers of radon-induced lung cancer risk: a genome-wide interaction study in former uranium miners. Int Arch Occup Environ Health. 91:937–950.
  • Rosenblatt E, Izewska J, Anacak Y, Pynda Y, Scalliet P, Boniol M, Autier P. 2013. Radiotherapy capacity in European countries: an analysis of the Directory of Radiotherapy Centers (DIRAC) database. Lancet Oncol. 14:e79–e86.
  • Schmitz A, Bayer J, Dechamps N, Goldin L, Thomas G. 2007. Heritability of susceptibility to ionizing radiation-induced apoptosis of human lymphocyte subpopulations. Int J Radiat Oncol Biol Phys. 68:1169–1177.
  • Schnarr K, Boreham D, Sathya J, Julian J, Dayes IS. 2009. Radiation-induced lymphocyte apoptosis to predict radiation therapy late toxicity in prostate cancer patients. Int J Radiat Oncol Biol Phys. 74:1424–1430.
  • Seibold P, Behrens S, Schmezer P, Helmbold I, Barnett G, Coles C, Yarnold J, Talbot CJ, Imai T, Azria D, et al. 2015. XRCC1 polymorphism associated with late toxicity after radiation therapy in breast cancer patients. Int J Radiat Oncol Biol Phys. 92:1084–1092.
  • Shore RE, Neriishi K, Nakashima E. 2010. Epidemiological studies of cataract risk at low to moderate radiation doses: (not) seeing is believing. Radiat Res. 181:889–894.
  • Sigurdson AJ, Stram DO. 2012. Genetic predisposition to radiation-related cancer and potential implications for risk assessment. Ann ICRP. 41:108–116.
  • Suit H, Goldberg S, Niemierko A, Ancukiewicz M, Hall E, Goitein M, Wong W, Paganetti H. 2007. Secondary carcinogenesis in patients treated with radiation: a review of data on radiation-induced cancers in human, non-human primate, canine and rodent subjects. Radiat Res. 167:12–42.
  • Talbot C, Tanteles G, Barnett G, Burnet N, Chang-Claude J, Coles C, Davidson S, nning A, Mills J, Murray R, et al. 2012. A replicated association between polymorphisms near TNFα and risk for adverse reactions to radiotherapy. Br J Cancer. 107:748–753.
  • Trimboli AJ, Cantemir-Stone CZ, Li F, Wallace JA, Merchant A, Creasap N, Thompson JC, Caserta E, Wang H, Chong J-L, et al. 2009. Pten in stromal fibroblasts suppresses mammary epithelial tumors. Nature. 461:1084–1091.
  • Tsuruoka C, Blyth BJ, Morioka T, Kaminishi M, Shinagawa M, Shimada Y, Kakinuma S. 2016. Sensitive detection of radiation-induced medulloblastomas after acute or protracted gamma-ray exposures in ptch1 heterozygous mice using a radiation-specific molecular signature. Radiat Res. 186:407–414.
  • UNSCEAR. 2008. Effects of ionizing radiation. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2006 Report, Vol. I. New York (NY): UNSCEAR.
  • van Oorschot B, Hovingh S, Dekker A, Stalpers LJ, Franken NA. 2016. Predicting radiosensitivity with gamma-H2AX foci assay after single high-dose-rate and pulsed dose-rate ionizing irradiation. Radiat Res. 185:190–198.
  • van Oorschot B, Hovingh SE, Moerland PD, Medema J, Stalpers L, Vrieling H, Franken N. 2014. Reduced activity of double-strand break repair genes in prostate cancer patients with late normal tissue radiation toxicity. Int J Radiat Oncol Biol Phys. 88:664–670.
  • Vandevoorde C, Depuydt J, Veldeman L, Neve W, Sebastià N, Wieme G, Baert A, Langhe S, Philippé J, Thierens H, et al. 2016. In vitro cellular radiosensitivity in relationship to late normal tissue reactions in breast cancer patients: a multi-endpoint case-control study. Int J Radiat Biol. 92:823–836.
  • Verbiest T, Finnon R, Brown N, Cruz-Garcia L, Finnon P, O’Brien G, Ross E, Bouffler S, Scudamore CL, Badie C. 2018. Tracking preleukemic cells in vivo to reveal the sequence of molecular events in radiation leukemogenesis. Leukemia. 32:1435–1444.
  • Vogin G, Bastogne T, Bodgi L, Gillet-Daubin J, Canet A, Pereira S, Foray N. 2018. The pATM Immunofluorescence assay: a high-performance radiosensitivity assay to predict post radiotherapy overreactions. Int J Radiat Oncol Biol Phys. 101:690–693.
  • Waugh APW, Beare DM, Arlett CF, Green MHL, Cole J. 1991. Comparative human cellular radiosensitivity: IV. The increased sensitivity of human neonatal cord blood lymphocytes to γ-irradiation compared with lymphocytes from children and adults. Int J Radiat Biol. 59:767–776.
  • Werbrouck J, De Ruyck K, Beels L, Vral A, Van Eijkeren M, De Neve W, Thierens H. 2010. Prediction of late normal tissue complications in RT treated gynaecological cancer patients: potential of the γ-H2AX foci assay and association with chromosomal radiosensitivity. Oncol Rep. 23:571–578.
  • West C, Azria D, Chang-Claude J, Davidson S, Lambin P, Rosenstein B, De Ruysscher D, Talbot C, Thierens H, Valdagni R, et al. 2014. The REQUITE project: validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality of life in cancer survivors. Clin Oncol. 26:739–742.
  • West CM, Barnett GC. 2011. Genetics and genomics of radiotherapy toxicity: towards prediction. Genome Med. 3:52.
  • West C, Rosenstein BS, Alsner J, Azria D, Barnett G, Begg A, Bentzen S, Burnet N, Chang CJ, Chuang E, et al. 2010. Establishment of a radiogenomics consortium. Int J Radiat Oncol Biol Phys. 76:1295–1296.
  • Wirsdörfer F, de Leve S, Jendrossek V. 2018. Combining radiotherapy and immunotherapy in lung cancer: can we expect limitations due to altered normal tissue toxicity? Int J Mol Sci. 20:24.
  • Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, Welch JS, Lamprecht TL, Shen D, Hundal J, Fulton RS, et al. 2015. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature. 518:552–555.
  • Zahnreich S, Ebersberger A, Karle H, Kaina B, Schmidberger H. 2016. Quantification of radiation biomarkers in leukocytes of breast cancer patients treated with different modalities of 3D-CRT or IMRT. Radiat Res. 186:508–519.

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