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Published in: BMC Geriatrics 1/2018

Open Access 01-12-2018 | Research Article

Rate of individuals with clearly increased radiosensitivity rise with age both in healthy individuals and in cancer patients

Authors: Barbara Schuster, Anna Ellmann, Theresa Mayo, Judith Auer, Matthias Haas, Markus Hecht, Rainer Fietkau, Luitpold V. Distel

Published in: BMC Geriatrics | Issue 1/2018

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Abstract

Background

The question of an age dependence of individual radiosensitivity has only marginally been studied so far. Therefore, we analyzed blood samples of healthy individuals and cancer patients of different ages to determine individual radiosensitivity.

Methods

Ex vivo irradiated blood samples of 595 individuals were tested. Chromosomes 1, 2 and 4 were stained by 3-color fluorescence in situ hybridization and aberrations were analyzed. Radiosensitivity was determined by the mean breaks per metaphase (B/M).

Results

Healthy individuals (mean age 50.7 years) had an average B/M value of 0.42 ± 0.104 and an increase of 0.0014B/M per year. The patients (mean age 60.4 years) had an average B/M value of 0.44 ± 0.150 and radiosensitivity did not change with age. In previous studies we found that from a value of 0.6B/M on an individual is considered to be distinctly radiosensitive. The portion of radiosensitive individuals (B/M > 0.6) increased in both cohorts with age.

Conclusion

Individual radiosensitivity rises continuously with age, yet with strong interindividual variation. No age related increase of radiosensitivity can be demonstrated in patients due to the strong interindividual variation. However among old cancer patients there is a higher probability to have patients with clearly increased radiosensitivity than at younger age.
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Literature
2.
go back to reference Lilla C, Ambrosone CB, Kropp S, Helmbold I, Schmezer P, von Fournier D, Haase W, Sautter-Bihl ML, Wenz F, Chang-Claude J. Predictive factors for late normal tissue complications following radiotherapy for breast cancer. Breast Cancer Res Treat. 2007;106(1):143–50.CrossRefPubMed Lilla C, Ambrosone CB, Kropp S, Helmbold I, Schmezer P, von Fournier D, Haase W, Sautter-Bihl ML, Wenz F, Chang-Claude J. Predictive factors for late normal tissue complications following radiotherapy for breast cancer. Breast Cancer Res Treat. 2007;106(1):143–50.CrossRefPubMed
3.
go back to reference Sedelnikova OA, Horikawa I, Redon C, Nakamura A, Zimonjic DB, Popescu NC, Bonner WM. Delayed kinetics of DNA double-strand break processing in normal and pathological aging. Aging Cell. 2008;7(1):89–100.CrossRefPubMed Sedelnikova OA, Horikawa I, Redon C, Nakamura A, Zimonjic DB, Popescu NC, Bonner WM. Delayed kinetics of DNA double-strand break processing in normal and pathological aging. Aging Cell. 2008;7(1):89–100.CrossRefPubMed
4.
go back to reference Endt H, Sprung CN, Keller U, Gaipl U, Fietkau R, Distel LV. Detailed analysis of DNA repair and senescence marker kinetics over the life span of a human fibroblast cell line. J Gerontol a-Biol. 2011;66(4):367–75.CrossRef Endt H, Sprung CN, Keller U, Gaipl U, Fietkau R, Distel LV. Detailed analysis of DNA repair and senescence marker kinetics over the life span of a human fibroblast cell line. J Gerontol a-Biol. 2011;66(4):367–75.CrossRef
5.
go back to reference Rube CE, Fricke A, Widmann TA, Furst T, Madry H, Pfreundschuh M, Rube C. Accumulation of DNA Damage in Hematopoietic Stem and Progenitor Cells during Human Aging. PLoS One. 2011;6(3) Rube CE, Fricke A, Widmann TA, Furst T, Madry H, Pfreundschuh M, Rube C. Accumulation of DNA Damage in Hematopoietic Stem and Progenitor Cells during Human Aging. PLoS One. 2011;6(3)
6.
go back to reference Wenger B, Schwegler M, Brunner M, Daniel C, Schmidt M, Fietkau R, Distel LV. PML-nuclear bodies decrease with age and their stress response is impaired in aged individuals. BMC Geriatr. 2014;14:42.CrossRefPubMedPubMedCentral Wenger B, Schwegler M, Brunner M, Daniel C, Schmidt M, Fietkau R, Distel LV. PML-nuclear bodies decrease with age and their stress response is impaired in aged individuals. BMC Geriatr. 2014;14:42.CrossRefPubMedPubMedCentral
7.
go back to reference Peuckmann V, Ekholm O, Rasmussen NK, Groenvold M, Christiansen P, Moller S, Eriksen J, Sjogren P. Chronic pain and other sequelae in long-term breast cancer survivors: nationwide survey in Denmark. Eur J Pain. 2009;13(5):478–85.CrossRefPubMed Peuckmann V, Ekholm O, Rasmussen NK, Groenvold M, Christiansen P, Moller S, Eriksen J, Sjogren P. Chronic pain and other sequelae in long-term breast cancer survivors: nationwide survey in Denmark. Eur J Pain. 2009;13(5):478–85.CrossRefPubMed
8.
go back to reference Dehing-Oberije C, De Ruysscher D, van Baardwijk A, Yu S, Rao B, Lambin P. The importance of patient characteristics for the prediction of radiation-induced lung toxicity. Radiother Oncol. 2009;91(3):421–6.CrossRefPubMed Dehing-Oberije C, De Ruysscher D, van Baardwijk A, Yu S, Rao B, Lambin P. The importance of patient characteristics for the prediction of radiation-induced lung toxicity. Radiother Oncol. 2009;91(3):421–6.CrossRefPubMed
9.
go back to reference Collette S, Collette L, Budiharto T, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, Jager JJ, Hoogenraad W, et al. Predictors of the risk of fibrosis at 10 years after breast conserving therapy for early breast cancer: a study based on the EORTC trial 22881-10882 'boost versus no boost'. Eur J Cancer. 2008;44(17):2587–99.CrossRefPubMed Collette S, Collette L, Budiharto T, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, Jager JJ, Hoogenraad W, et al. Predictors of the risk of fibrosis at 10 years after breast conserving therapy for early breast cancer: a study based on the EORTC trial 22881-10882 'boost versus no boost'. Eur J Cancer. 2008;44(17):2587–99.CrossRefPubMed
10.
go back to reference Barnett GC, Wilkinson JS, Moody AM, Wilson CB, Twyman N, Wishart GC, Burnet NG, Coles CE. The Cambridge breast intensity-modulated radiotherapy trial: patient- and treatment-related factors that influence late toxicity. Clin Oncol. 2011;23(10):662–73.CrossRef Barnett GC, Wilkinson JS, Moody AM, Wilson CB, Twyman N, Wishart GC, Burnet NG, Coles CE. The Cambridge breast intensity-modulated radiotherapy trial: patient- and treatment-related factors that influence late toxicity. Clin Oncol. 2011;23(10):662–73.CrossRef
11.
go back to reference Scott D. Chromosomal radiosensitivity, cancer predisposition and response to radiotherapy. Strahlenther Onkol. 2000;176(5):229–34.CrossRefPubMed Scott D. Chromosomal radiosensitivity, cancer predisposition and response to radiotherapy. Strahlenther Onkol. 2000;176(5):229–34.CrossRefPubMed
12.
go back to reference Jones LA, Scott D, Cowan R, Roberts SA. Abnormal radiosensitivity of lymphocytes from breast cancer patients with excessive normal tissue damage after radiotherapy: chromosome aberrations after low dose-rate irradiation. Int J Radiat Biol. 1995;67 Jones LA, Scott D, Cowan R, Roberts SA. Abnormal radiosensitivity of lymphocytes from breast cancer patients with excessive normal tissue damage after radiotherapy: chromosome aberrations after low dose-rate irradiation. Int J Radiat Biol. 1995;67
13.
go back to reference Dunst J, Neubauer S, Becker A, Gebhart E. Chromosomal in vitro radiosensitivity of lymphocytes in radiotherapy patients and AT-homozygotes. Strahlenther Onkol. 1998;174 Dunst J, Neubauer S, Becker A, Gebhart E. Chromosomal in vitro radiosensitivity of lymphocytes in radiotherapy patients and AT-homozygotes. Strahlenther Onkol. 1998;174
14.
go back to reference Neubauer S, Dunst J, Gebhart E. The impact of complex chromosomal rearrangements on the detection of radiosensitivity in cancer patients. Radiother Oncol. 1997;43(2):189–95.CrossRefPubMed Neubauer S, Dunst J, Gebhart E. The impact of complex chromosomal rearrangements on the detection of radiosensitivity in cancer patients. Radiother Oncol. 1997;43(2):189–95.CrossRefPubMed
15.
go back to reference Baeyens A, Thierens H, Claes K, Poppe B, Messiaen L, De Ridder L, Vral A. Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition. Br J Cancer. 2002;87(12):1379–85.CrossRefPubMedPubMedCentral Baeyens A, Thierens H, Claes K, Poppe B, Messiaen L, De Ridder L, Vral A. Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition. Br J Cancer. 2002;87(12):1379–85.CrossRefPubMedPubMedCentral
16.
go back to reference Hoeller U, Borgmann K, Bonacker M, Kuhlmey A, Bajrovic A, Jung H, Alberti W, Dikomey E. Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer. Radiother Oncol. 2003;69 Hoeller U, Borgmann K, Bonacker M, Kuhlmey A, Bajrovic A, Jung H, Alberti W, Dikomey E. Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer. Radiother Oncol. 2003;69
17.
go back to reference Huber R, Braselmann H, Geinitz H, Jaehnert I, Baumgartner A, Thamm R, Figel M, Molls M, Zitzelsberger H. Chromosomal radiosensitivity and acute radiation side effects after radiotherapy in tumour patients--a follow-up study. Radiat Oncol. 2011;6:32.CrossRefPubMedPubMedCentral Huber R, Braselmann H, Geinitz H, Jaehnert I, Baumgartner A, Thamm R, Figel M, Molls M, Zitzelsberger H. Chromosomal radiosensitivity and acute radiation side effects after radiotherapy in tumour patients--a follow-up study. Radiat Oncol. 2011;6:32.CrossRefPubMedPubMedCentral
18.
go back to reference Scott D, Spreadborough AR, Jones LA, Roberts SA, Moore CJ. Chromosomal radiosensitivity in G2-phase lymphocytes as an indicator of cancer predisposition. Radiat Res. 1996;145(1):3–16.CrossRefPubMed Scott D, Spreadborough AR, Jones LA, Roberts SA, Moore CJ. Chromosomal radiosensitivity in G2-phase lymphocytes as an indicator of cancer predisposition. Radiat Res. 1996;145(1):3–16.CrossRefPubMed
19.
go back to reference Grabenbauer GG, Lahmer G, Distel L, Niedobitek G. Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma. Clin Cancer Res. 2006;12(11 Pt 1):3355–60.CrossRefPubMed Grabenbauer GG, Lahmer G, Distel L, Niedobitek G. Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma. Clin Cancer Res. 2006;12(11 Pt 1):3355–60.CrossRefPubMed
20.
go back to reference Tucker JD, Morgan WF, Awa AA, Bauchinger M, Blakey D, Cornforth MN, Littlefield LG, Natarajan AT, Shasserre C. A proposed system for scoring structural aberrations detected by chromosome painting. Cytogenet Cell Genet. 1995;68(3–4):211–21.CrossRefPubMed Tucker JD, Morgan WF, Awa AA, Bauchinger M, Blakey D, Cornforth MN, Littlefield LG, Natarajan AT, Shasserre C. A proposed system for scoring structural aberrations detected by chromosome painting. Cytogenet Cell Genet. 1995;68(3–4):211–21.CrossRefPubMed
21.
go back to reference Savage JR, Simpson P. On the scoring of FISH-"painted" chromosome-type exchange aberrations. Mutat Res. 1994;307(1):345–53.CrossRefPubMed Savage JR, Simpson P. On the scoring of FISH-"painted" chromosome-type exchange aberrations. Mutat Res. 1994;307(1):345–53.CrossRefPubMed
22.
go back to reference Barber JB, Burrill W, Spreadborough AR, Levine E, Warren C, Kiltie AE, Roberts SA, Scott D. Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer. Radiother Oncol. 2000;55(2):179–86.CrossRefPubMed Barber JB, Burrill W, Spreadborough AR, Levine E, Warren C, Kiltie AE, Roberts SA, Scott D. Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer. Radiother Oncol. 2000;55(2):179–86.CrossRefPubMed
23.
go back to reference Baria K, Warren C, Roberts SA, West CM, Scott D. Chromosomal radiosensitivity as a marker of predisposition to common cancers? Br J Cancer. 2001;84(7):892–6.CrossRefPubMedPubMedCentral Baria K, Warren C, Roberts SA, West CM, Scott D. Chromosomal radiosensitivity as a marker of predisposition to common cancers? Br J Cancer. 2001;84(7):892–6.CrossRefPubMedPubMedCentral
24.
go back to reference Beaton LA, Marro L, Samiee S, Malone S, Grimes S, Malone K, Wilkins RC. Investigating chromosome damage using fluorescent in situ hybridization to identify biomarkers of radiosensitivity in prostate cancer patients. Int J Radiat Biol. 2013;89(12):1087–93.CrossRefPubMed Beaton LA, Marro L, Samiee S, Malone S, Grimes S, Malone K, Wilkins RC. Investigating chromosome damage using fluorescent in situ hybridization to identify biomarkers of radiosensitivity in prostate cancer patients. Int J Radiat Biol. 2013;89(12):1087–93.CrossRefPubMed
25.
go back to reference Popanda O, Ebbeler R, Twardella D, Helmbold I, Gotzes F, Schmezer P, Thielmann HW, von Fournier D, Haase W, Sautter-Bihl ML, et al. Radiation-induced DNA damage and repair in lymphocytes from breast cancer patients and their correlation with acute skin reactions to radiotherapy. Int J Radiat Oncol Biol Phys. 2003;55(5):1216–25.CrossRefPubMed Popanda O, Ebbeler R, Twardella D, Helmbold I, Gotzes F, Schmezer P, Thielmann HW, von Fournier D, Haase W, Sautter-Bihl ML, et al. Radiation-induced DNA damage and repair in lymphocytes from breast cancer patients and their correlation with acute skin reactions to radiotherapy. Int J Radiat Oncol Biol Phys. 2003;55(5):1216–25.CrossRefPubMed
26.
go back to reference Auer J, Keller U, Schmidt M, Ott O, Fietkau R, Distel LV. Individual radiosensitivity in a breast cancer collective is changed with the patients' age. Radiol Oncol. 2014;48(1):80–6.CrossRefPubMedPubMedCentral Auer J, Keller U, Schmidt M, Ott O, Fietkau R, Distel LV. Individual radiosensitivity in a breast cancer collective is changed with the patients' age. Radiol Oncol. 2014;48(1):80–6.CrossRefPubMedPubMedCentral
27.
go back to reference Gebhart E, Neubauer S, Schmitt G, Birkenhake S, Dunst J. Use of a three-color chromosome in situ suppression technique for the detection of past radiation exposure. Radiat Res. 1996;145(1):47–52.CrossRefPubMed Gebhart E, Neubauer S, Schmitt G, Birkenhake S, Dunst J. Use of a three-color chromosome in situ suppression technique for the detection of past radiation exposure. Radiat Res. 1996;145(1):47–52.CrossRefPubMed
28.
go back to reference Keller U, Kuechler A, Liehr T, Muller E, Grabenbauer G, Sauer R, Distel L. Impact of various parameters in detecting chromosomal aberrations by FISH to describe Radiosensitivity. Strahlenther Onkol. 2004;180(5):289–96.CrossRefPubMed Keller U, Kuechler A, Liehr T, Muller E, Grabenbauer G, Sauer R, Distel L. Impact of various parameters in detecting chromosomal aberrations by FISH to describe Radiosensitivity. Strahlenther Onkol. 2004;180(5):289–96.CrossRefPubMed
29.
go back to reference Hasegawa T, Someya M, Hori M, Matsumoto Y, Nakata K, Nojima M, Kitagawa M, Tsuchiya T, Masumori N, Hasegawa T, et al. Expression of Ku70 predicts results of radiotherapy in prostate cancer. Strahlenther Onkol. 2017;193(1):29–37.CrossRefPubMed Hasegawa T, Someya M, Hori M, Matsumoto Y, Nakata K, Nojima M, Kitagawa M, Tsuchiya T, Masumori N, Hasegawa T, et al. Expression of Ku70 predicts results of radiotherapy in prostate cancer. Strahlenther Onkol. 2017;193(1):29–37.CrossRefPubMed
30.
go back to reference Oskan F, Becker G, Bleif M. Specific toxicity after stereotactic body radiation therapy to the central chest : a comprehensive review. Strahlenther Onkol. 2017;193(3):173–84.CrossRefPubMed Oskan F, Becker G, Bleif M. Specific toxicity after stereotactic body radiation therapy to the central chest : a comprehensive review. Strahlenther Onkol. 2017;193(3):173–84.CrossRefPubMed
31.
32.
go back to reference Nagy R, Sweet K, Eng C. Highly penetrant hereditary cancer syndromes. Oncogene. 2004;23(38):6445–70.CrossRefPubMed Nagy R, Sweet K, Eng C. Highly penetrant hereditary cancer syndromes. Oncogene. 2004;23(38):6445–70.CrossRefPubMed
33.
go back to reference Houlston RS, Peto J. The search for low-penetrance cancer susceptibility alleles. Oncogene. 2004;23(38):6471–6.CrossRefPubMed Houlston RS, Peto J. The search for low-penetrance cancer susceptibility alleles. Oncogene. 2004;23(38):6471–6.CrossRefPubMed
34.
go back to reference Dite GS, Jenkins MA, Southey MC, Hocking JS, Giles GG, McCredie MR, Venter DJ, Hopper JL. Familial risks, early-onset breast cancer, and BRCA1 and BRCA2 germline mutations. J Natl Cancer Inst. 2003;95(6):448–57.CrossRefPubMed Dite GS, Jenkins MA, Southey MC, Hocking JS, Giles GG, McCredie MR, Venter DJ, Hopper JL. Familial risks, early-onset breast cancer, and BRCA1 and BRCA2 germline mutations. J Natl Cancer Inst. 2003;95(6):448–57.CrossRefPubMed
35.
go back to reference Distel LV, Keller U, Neubauer S: Three-color FISH for the detection of individual Radiosensitivity: springer; 2009. Distel LV, Keller U, Neubauer S: Three-color FISH for the detection of individual Radiosensitivity: springer; 2009.
36.
go back to reference Distel LV, Neubauer S, Keller U, Sprung CN, Sauer R, Grabenbauer GG. Individual differences in chromosomal aberrations after in vitro irradiation of cells from healthy individuals, cancer and cancer susceptibility syndrome patients. Radiother Oncol. 2006;81(3):257–63.CrossRefPubMed Distel LV, Neubauer S, Keller U, Sprung CN, Sauer R, Grabenbauer GG. Individual differences in chromosomal aberrations after in vitro irradiation of cells from healthy individuals, cancer and cancer susceptibility syndrome patients. Radiother Oncol. 2006;81(3):257–63.CrossRefPubMed
37.
go back to reference Bakhmutsky MV, Joiner MC, Jones TB, Tucker JD. Differences in cytogenetic sensitivity to ionizing radiation in newborns and adults. Radiat Res. 2014;181(6):605–16.CrossRefPubMed Bakhmutsky MV, Joiner MC, Jones TB, Tucker JD. Differences in cytogenetic sensitivity to ionizing radiation in newborns and adults. Radiat Res. 2014;181(6):605–16.CrossRefPubMed
38.
go back to reference Pajic J, Rakic B, Rovcanin B, Jovicic D, Novakovic I, Milovanovic A, Pajic V. Inter-individual variability in the response of human peripheral blood lymphocytes to ionizing radiation: comparison of the dicentric and micronucleus assays. Radiat Environ Biophys. 2015;54(3):317–25.CrossRefPubMed Pajic J, Rakic B, Rovcanin B, Jovicic D, Novakovic I, Milovanovic A, Pajic V. Inter-individual variability in the response of human peripheral blood lymphocytes to ionizing radiation: comparison of the dicentric and micronucleus assays. Radiat Environ Biophys. 2015;54(3):317–25.CrossRefPubMed
39.
go back to reference Baeyens A, Van Den Broecke R, Makar A, Thierens H, De Ridder L, Vral A. Chromosomal radiosensitivity in breast cancer patients: influence of age of onset of the disease. Oncol Rep. 2005;13(2):347–53.PubMed Baeyens A, Van Den Broecke R, Makar A, Thierens H, De Ridder L, Vral A. Chromosomal radiosensitivity in breast cancer patients: influence of age of onset of the disease. Oncol Rep. 2005;13(2):347–53.PubMed
40.
go back to reference Schilling S, Keller U, Sprung CN, Weise A, Grabenbauer GG, Sauer R, Distel L. Breakpoint locations within chromosomes 1, 2, and 4 of patients with increased radiosensitivity. Cancer Genet Cytogenet. 2006;168(1):1–10.CrossRefPubMed Schilling S, Keller U, Sprung CN, Weise A, Grabenbauer GG, Sauer R, Distel L. Breakpoint locations within chromosomes 1, 2, and 4 of patients with increased radiosensitivity. Cancer Genet Cytogenet. 2006;168(1):1–10.CrossRefPubMed
42.
go back to reference Tucker JD, Ramsey MJ, Lee DA, Minkler JL. Validation of chromosome painting as a biodosimeter in human peripheral lymphocytes following acute exposure to ionizing radiation in vitro. Int J Radiat Biol. 1993;64(1):27–37.CrossRefPubMed Tucker JD, Ramsey MJ, Lee DA, Minkler JL. Validation of chromosome painting as a biodosimeter in human peripheral lymphocytes following acute exposure to ionizing radiation in vitro. Int J Radiat Biol. 1993;64(1):27–37.CrossRefPubMed
43.
go back to reference Kuechler A, Neubauer S, Grabenbauer GG, Claussen U, Liehr T, Sauer R, Wendt TG. Is 24-color FISH detection of in-vitro radiation-induced chromosomal aberrations suited to determine individual intrinsic radiosensitivity? Strahlenther Onkol. 2002;178(4):209–15.CrossRefPubMed Kuechler A, Neubauer S, Grabenbauer GG, Claussen U, Liehr T, Sauer R, Wendt TG. Is 24-color FISH detection of in-vitro radiation-induced chromosomal aberrations suited to determine individual intrinsic radiosensitivity? Strahlenther Onkol. 2002;178(4):209–15.CrossRefPubMed
Metadata
Title
Rate of individuals with clearly increased radiosensitivity rise with age both in healthy individuals and in cancer patients
Authors
Barbara Schuster
Anna Ellmann
Theresa Mayo
Judith Auer
Matthias Haas
Markus Hecht
Rainer Fietkau
Luitpold V. Distel
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2018
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/s12877-018-0799-y

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