Reader TTS

ABSTRACT Do second primary cancers in humans arise from radiation-induced somatic genomic instability after radiotherapy for the first malignancy? The amount of truly pertinent human

information on this issue is sparse, leading to the conclusion that we cannot confirm or refute that instability induction by radiation is involved. However, the _in vitro_ findings of

radiation-induced genomic instability through bystander effects or increased mutation rates in cell progeny of apparently normal but irradiated cells are provocative and their

transferability to human _in vivo_ biology deserves further investigation. We describe possible animal and human studies to stimulate ideas, but the collaborative commitment of multiple

large institutions to tumor tissue procurement and retrieval will be essential. In addition, detecting the temporal progression of genomic instability and identifying the salient genetic

events as being radiation-induced will be pivotal. Execution of some of the studies suggested is not possible now, but applying next-generation methods could bring the concepts to fruition.

As nearly one in 10 cancer diagnoses are second (or higher) malignancies, it is important to understand the contribution of radiotherapy to second cancer induction and pursue

well-coordinated efforts to determine the role of induced genomic instability. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this

article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in

* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS REPEATED IONIZING RADIATION EXPOSURE INDUCES TRIP13 EXPRESSION,

CONFERRING RADIORESISTANCE IN LUNG CANCER CELLS Article Open access 06 January 2025 P53 DYNAMICS VARY BETWEEN TISSUES AND ARE LINKED WITH RADIATION SENSITIVITY Article Open access 09

February 2021 IONIZING RADIATION RESULTS IN A MIXTURE OF CELLULAR OUTCOMES INCLUDING MITOTIC CATASTROPHE, SENESCENCE, METHUOSIS, AND IRON-DEPENDENT CELL DEATH Article Open access 23 November

2020 ABBREVIATIONS * AML: acute myeloblastic leukemia * CGH: comparative genomic hybridization * CT: chemotherapy * +FH: positive family history of cancer * GBM: glioblastoma multiforme *

HL: Hodgkin's lymphoma * LOH: loss of heterozygosity * MDS: myelodysplastic syndrome * MPNST: malignant peripheral nerve sheath tumor * NF2: neurofibromatosis type 2 * RB:

retinoblastoma * RER+: replication error or mutator phenotype * RIM: radiation-induced meningioma * XRT: radiotherapy REFERENCES * Alter BP and Young NS . (1998). _Hematology of Infancy and

Childhood_, Vol. 1. Nathan DG and Oski FA (eds). Saunders: Philadelphia, PA, pp. 259–272. Google Scholar  * Backlund MG, Trasti SL, Backlund DC, Cressman VL, Godfrey V and Koller BH .

(2001). _Cancer Res._, 61, 6577–6582. * Barcellos-Hoff MH and Brooks AL . (2001). _Radiat. Res._, 156, 618–627. * Bauchinger M . (1998). _Mutat. Res._, 404, 89–96. * Behrens C, Travis LB,

Wistuba II, Davis S, Maitra A, Clarke EA, Lynch CF, Glimelius B, Wiklund T, Tarone R and Gazdar AF . (2000). _Cancer Epidemiol. Biomarkers Prev._, 9, 1027–1035. * Ben-Yehuda D, Krichevsky S,

Caspi O, Rund D, Polliack A, Abeliovich D, Zelig O, Yahalom V, Paltiel O, Or R, Peretz T, Ben-Neriah S, Yehuda O and Rachmilewitz EA . (1996). _Blood_, 88, 4296–4303. * Berwick M, Matullo G

and Vineis P . (2002). _Biomarkers of Environmentally Associated Disease: Technologies, Concepts and Perspectives._ Wilson SH and Suk WA (eds). Lewis Publishers: Boca Raton, FL, pp. 84–105.

Google Scholar  * Berwick M and Vineis P . (2000). _J. Natl. Cancer Inst._, 92, 874–897. * Bhatia S, Robison LL, Oberlin O, Greenberg M, Bunin G, Fossati-Bellani F and Meadows AT . (1996).

_N. Engl. J. Med._, 334, 745–751. * Boice Jr JD, Blettner M, Kleinerman RA, Stovall M, Moloney WC, Engholm G, Austin DF, Bosch A, Cookfair DL, Krementz ET, Latourette HB, Peters LJ, Schulz

MD, Lundell M, Pettersson F, Storm HH, Bell CMJ, Coleman MP, Fraser P, Palmer M, Prior P, Choi NW, Hislp TG, Koch M, Robb D, Robson D, Spengler RF, von Fournier D, Frishchkorn R, Lochmüller

H, Pompe-Kirn V, Rimpela A, KjØrstad K, Pejovic MH, Sigurdsson K, Pisani P, Kucera H and Hutchison GB . (1987). _J. Natl. Cancer Inst._, 79, 1295–1311. * Boice Jr JD, Engholm G, Kleinerman

RA, Blettner M, Stovall M, Lisco H, Moloney WC, Austin DF, Bosch A, Cookfair DL, Krementz ET, Latourette HB, Merrill JA, Peters LJ, Schulz MD, Storm HH, Björkholm E, Pettersson F, Bell CMJ,

Coleman MP, Fraser P, Neal FE, Prior P, Choi WN, Hislop TG, Koch M, Kreiger N, Robb D, Robson D, Thomson DH, Lochmüller H, vonFournier D, Frischkorn R, KjØrstad KK, Rimpela A, Pejovich M-H,

Kirn VP, Stankusova H, Berrino F, Sigurdsson K, Hutchison GB and MacMahon B . (1988). _Radiat. Res._, 116, 3–55. * Boice Jr JD, Land CE and Preston DL . (1996). _Cancer Epidemiology and

Prevention_, 2nd edn. Schottenfeld D and Fraumeni Jr JF (eds). Oxford University Press: New York, pp. 319–354. Google Scholar  * Boivin JF, Hutchison GB, Zauber AG, Bernstein L, Davis FG,

Michel RP, Zanke B, Tan CT, Fuller LM, Mauch P and Ultman JE . (1995). _J. Natl. Cancer Inst._, 87, 732–741. * Brat DJ, James CD, Jedlicka AE, Connolly DC, Chang E, Castellani RJ, Schmid M,

Schiller M, Carson DA and Burger PC . (1999). _Am. J. Pathol._, 154, 1431–1438. * Chauveinc L, Dutrillaux AM, Validire P, Padoy E, Sabatier L, Courturier J and Dutrillaux B . (1999). _Cancer

Genet. Cytogenet._, 114, 1–8. * Chen Z and Sandberg AA . (2002). _Am. J. Med. Genet._, 115, 130–141. * Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socie G, Travis LB, Horowitz MM,

Witherspoon RP, Hoover RN, Sobocinski KA, Fraumeni Jr JF and Boice Jr JD . (1997). _N. Engl. J. Med._, 336, 897–904. * De Benedetti VMG, Travis LB, Welsh JA, van Leeuwen FE, Stovall M,

Clarke EA, Boice Jr JD and Bennett WP . (1996). _Cancer Epidemiol. Biomarkers Prev._, 5, 93–98. * Deeg HJ, Socie G, Schoch G, Henry-Amar M, Witherspoon RP, Devergie A, Sullivan KM, Gluckman

E and Storb R . (1996). _Blood_, 87, 386–392. * De Vathaire F, Hardiman C, Shamsaldin A, Campbell S, Grimaud E, Hawkins M, Raquin M, Oberlin O, Diallo I, Zucker JM, Panis X, Lagrange JL,

Daly-Schveitzer N, Lemerle J, Chavaudra J, Schlumberger M and Bonaiti C . (1999). _Arch. Intern. Med._, 159, 2713–2719. * Dores GM, Metayer C, Curtis RE, Lynch CF, Clarke EA, Glimelius B,

Storm H, Pukkala E, van Leeuwen FE, Holowaty EJ, Andersson M, Wiklund T, Joensuu T, van't Veer MB, Stovall M, Gospodarowicz M and Travis LB . (2002). _J. Clin. Oncol._, 20, 3484–3494. *

Fang NY, Greiner TC, Weisenburger DD, Chan WC, Vose JM, Smith LM, Armitage JO, Mayer RA, Pike BL, Collins FS and Hacia JG . (2003). _Proc. Natl. Acad. Sci. USA_, 100, 5372–5377. * Ferguson

DO and Alt FW . (2001). _Oncogene_, 20, 5572–5579. * Finnon P, Moquet JE, Edwards AA and Lloyd DC . (1999). _Int. J. Radiat. Biol._, 75, 1215–1222. * Friedberg EC and Meira LB . (2003). _DNA

Repair_, 2, 501–530. * Gafanovich A, Ramu N, Krichevsky S, Pe'er S, Amir G and Ben-Yehuda D . (1999). _Cancer_, 85, 504–510. * Gilbert ES, Stovall M, Gospodarowicz M, van Leeuwen FE,

Andersson M, Glimelius B, Joensuu T, Lynch CF, Curtis RE, Holowaty E, Storm H, Pukkala E, van't Veer MD, Fraumeni Jr JF, Boice Jr JD, Clarke EA and Travis LB . (2003). _Radiat. Res._,

159, 161–173. * Goodman MF . (2002). _Annu. Rev. Biochem._, 71, 17–50. * Gray JW and Collins C . (2000). _Carcinogenesis_, 21, 443–452. * Horiike S, Misawa S, Kaneko H, Sasai Y, Kobayashi M,

Fujii H, Tanaka S, Yagita M, Abe T, Kashima K and Taniwaki M . (1999). _Leukemia_, 13, 1235–1242. * Inskip PD . (1999). _Multiple Primary Cancers._ Neugut AI, Meadows AT and Robinson E

(eds). Lippincott Williams and Wilkins: Philadelphia, pp. 91–135. Google Scholar  * Kaldor JM, Day NE, Bell J, Clarke EA, Langmark F, Karjalainen S, Band P, Pedersen D, Choi W, Blair V,

Henry-Amar M, Prior P, Assouline D, Pompe-Kirn V, Cartwright RA, Koch M, Arslan A, Fraser P, Sutcliffe SB, Host H, Hakama M and Stovall M . (1992). _Int. J. Cancer_, 52, 677–681. *

Kleinerman RA, Littlefield LG, Tarone RE, Sayer AM, Hildreth NG, Pottern LM, Machado SG and Boice Jr JD . (1990). _Radiat. Res._, 123, 93–101. * Kodama Y, Pawel D, Nakamura N, Preston D,

Honda T, Itoh M, Nakano MK, Ohtaki K, Funamoto S and Awa AA . (2001). _Radiat. Res._, 156, 337–346. * Lefevre S-H, Bogt N, Dutrillaux A-M, Chauveinc L, Stoppa-Lyonnet D, Doz F, Desjardins L,

Dutrillaux B, Chevillard S and Malfoy B . (2001). _Oncogene_, 20, 8092–8099. * Lindahl T . (1993). _Nature_, 362, 709–715. * Little JB . (2000). _Carcinogenesis_, 21, 397–404. * Loeb LA,

Loeb KR and Anderson JP . (2003). _Proc. Natl. Acad. Sci. USA_, 100, 776–781. * Lorimore SA and Wright EG . (2003). _Int. J. Radiat. Biol._, 79, 15–25. * Mendelsohn ML . (1995). _Modeling of

Biological Effects and Risks of Radiation Exposure._ Inaba J and Kobayashi S (eds). National Institute of Radiological Sciences: Chiba, Japan, pp. 185–192. Google Scholar  * Mertens F,

Larramendy ML, Gustavsson A, Gisselsson D, Rydholm A, Brosjo O, Mitelman F, Knuutila YS and Mandahl N . (2000). _Cancer Genet. Cytogenet._, 116, 89–96. * Mohrenweiser HW, Wilson III DM and

Jones IM . (2003). _Mutat. Res._, 526, 93–125. * Morgan WF . (2003a). _Radiat. Res._, 159, 567–580. * Morgan WF . (2003b). _Radiat. Res._, 159, 581–596. * Platz EA, Wiencke JK, Kelsey KT,

Janower ML, Schottenfeld D, Travis LB and Goldman MB . (2000). _Int. J. Radiat. Biol._, 76, 955–961. * Robison LL, Mertens AC, Boice JD, Breslow NE, Donaldson SS, Green DM, Li FP, Meadows

AT, Mulvihill JJ, Neglia JP, Nesbit ME, Paker RJ, Potter JD, Sklar CA, Smith MA, Stovall M, Strong LC, Yasui Y and Zeltzer LK . (2002). _Med. Pediatr. Oncol._, 38, 229–239. * Ronen A and

Glickman BW . (2001). _Environ. Mol. Mutagen._, 37, 241–283. * Shoshan Y, Chernova O, Jeun S-S, Somerville RP, Israel Z, Barnett GH and Cowell JK . (2000). _J. Neuropathol. Exp. Neurol._,

59, 614–620. * Swerdlow AJ, Douglas AJ, Vaughn Hudson G, Vaughan Hudson B, Bennett MH and MacLennan KA . (1992). _BMJ_, 304, 1137–1143. * Tarkkanen M, Wiklund TA, Virolainen MJ, Larramendy

ML, Mandahl N, Mertens F, Blomqvist CP, Tukiainen EJ, Miettinen MMA, Elomaa AI and Knuutila YS . (2001). _Cancer_, 92, 1992–1998. * Travis LB, Gospodarowicz M, Curtis RE, Clarke EA,

Andersson M, Glimelius B, Joensuu T, Lynch CF, van Leeuwen FE, Holowaty E, Storm H, Glimelius I, Pukkala E, Stovall M, Fraumeni Jr JF, Boice Jr JD and Gilbert E . (2002). _J. Natl. Cancer

Inst._, 94, 182–192. * Travis LB, Andersson M, Gospodarowicz M, van Leeuwen FE, Bergfeldt K, Lynch CF, Curtis RE, Kohler BA, Wiklund T, Storm H, Holowaty E, Hall P, Pukkala E, Sleijfer DT,

Clarke EA, Boice Jr JD, Stovall M and Gilbert E . (2000). _J. Natl. Cancer Inst._, 92, 1165–1171. * Tucker MA, Coleman CN, Cox RS, Barghese A and Rosenberg SA . (1988). _N. Engl. J. Med._,

318, 76–81. * Tucker MA, Morris Jones PH, Boice Jr JD, Robison LL, Stone BJ, Stovall M, Jenkin RDT, Lubin JH, Baum ES, Siegel SE, Meadows AT, Hoover RN and Fraumeni Jr JF . (1991). _Cancer

Res._, 51, 2885–2888. * Tucker JD, Ramsey MJ, Lee DA and Minkler JL . (1993). _Int. J. Radiat. Biol._, 64, 27–37. * Ullrich RL and Ponnaiya B . (1998). _Int. J. Radiat. Biol._, 74, 747–754.

* van Leeuwen FE, Klokman WJ, Hagenbeek A, Noyon R, van den Belt-Dusebout AW, van Kerkhoff EH, van Heerde P and Somers R . (1994). _J. Clin. Oncol._, 12, 312–325. * Wood RD, Mitchell M,

Sgouros J and Lindahl T . (2001). _Science_, 291, 1284–1289 (Current supplement athttp://www.cgal.icnet.uk/DNA_Repair_Genes.html). * Wright EG . (1999). _J. Pathol._, 187, 19–27. * Yu Y,

Okayasu R, Weil MM, Silver A, McCarthy M, Zabriskie R, Long S, Cox R and Ullrich RL . (2001). _Cancer Res._, 61, 1820–1824. * Zablotska LB and Neugut AI . (2003). _Cancer_, 97, 1404–1411.

Download references ACKNOWLEDGEMENTS This work was performed under the auspices of the US Department of Energy by the University of California, Lawrence Livermore National Laboratory under

Contract No. W-7405-Eng-48. We thank Drs Peter Inskip, Joni Rutter and the anonymous reviewer for helpful comments on the manuscript. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division

of Cancer Epidemiology and Genetics, Radiation Epidemiology Branch, National Cancer Institute, NIH, DHHS, 6120 Executive Boulevard, EPS 7092, MSC 7238, Bethesda, 20892-7238, MD, USA Alice J

Sigurdson * Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, L-441, PO Box 808, 7000 East Avenue, Livermore, 94551-0808, CA, USA Irene M Jones Authors *

Alice J Sigurdson View author publications You can also search for this author inPubMed Google Scholar * Irene M Jones View author publications You can also search for this author inPubMed 

Google Scholar CORRESPONDING AUTHOR Correspondence to Alice J Sigurdson. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sigurdson, A., Jones, I. Second

cancers after radiotherapy: any evidence for radiation-induced genomic instability?. _Oncogene_ 22, 7018–7027 (2003). https://doi.org/10.1038/sj.onc.1206989 Download citation * Published: 13

October 2003 * Issue Date: 13 October 2003 * DOI: https://doi.org/10.1038/sj.onc.1206989 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get

shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * second

primary cancer * radiation therapy * genomic instability * chromosomal instability * review