Radiation and Environmental Biophysics

, Volume 46, Issue 4, pp 383–394 | Cite as

Lung cancer risk of Mayak workers: modelling of carcinogenesis and bystander effect

  • P. JacobEmail author
  • R. Meckbach
  • M. Sokolnikov
  • V. V. Khokhryakov
  • E. Vasilenko
Original Paper


Lung cancer mortality in the period of 1948–2002 has been analysed for 6,293 male workers of the Mayak Production Association, for whose information on smoking, annual external doses and annual lung doses due to plutonium exposures was available. Individual likelihoods were maximized for the two-stage clonal expansion (TSCE) model of carcinogenesis and for an empirical risk model. Possible detrimental and protective bystander effects on mutation and malignant transformation rates were taken into account in the TSCE model. Criteria for non-nested models were used to evaluate the quality of fit. Data were found to be incompatible with the model including a detrimental bystander effect. The model with a protective bystander effect did not improve the quality of fit over models without a bystander effect. The preferred TSCE model was sub-multiplicative in the risks due to smoking and internal radiation, and more than additive. Smoking contributed 57% to the lung cancer deaths, the interaction of smoking and radiation 27%, radiation 10%, and others cause 6%. An assessment of the relative biological effectiveness of plutonium was consistent with the ICRP recommended value of 20. At age 60 years, the excess relative risk (ERR) per lung dose was 0.20 (95% CI: 0.13; 0.40) Sv−1, while the excess absolute risk (EAR) per lung dose was 3.2 (2.0; 6.2) per 104 PY Sv. With increasing age attained the ERR decreased and the EAR increased. In contrast to the atomic bomb survivors, a significant elevated lung cancer risk was also found for age attained younger than 55 years. For cumulative lung doses below 5 Sv, the excess risk depended linearly on dose. The excess relative risk was significantly lower in the TSCE model for ages attained younger than 55 than that in the empirical model. This reflects a model uncertainty in the results, which is not expressed by the standard statistical uncertainty bands.


Plutonium Bystander Effect Relative Biological Effectiveness Intermediate Cell Lung Cancer Mortality 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Nina Koshurnikova for stimulating discussions. The work has been supported by the German Federal Ministry of Environment, Nature Preservation and Reactor Safety, and the German Federal Office of Radiation Protection under contract number StSch 4479.


  1. 1.
    Brenner DJ, Doll R, Goodhead DT, Hall EJ, Land CE, Little JB, Lubin JH, Preston DL, Preston RJ, Puskin JS, Ron E, Sachs RK, Samet JM, Setlow RB, Zaider M (2003) Cancer risk attributable to low doses of ionizing radiation: assessing what we really know. Proc Natl Acad Sci 100:13761–13766CrossRefADSGoogle Scholar
  2. 2.
    Sachs RK, Chan M, Hlatky L, Hahnfeldt P (2005) Modeling intercellular interactions during carcinogenesis. Radiat Res 164:324–331CrossRefGoogle Scholar
  3. 3.
    Moolgavkar SH, Venzon DJ (1979) Two-events models for carcinogenesis: incidence curves for childhood and adult tumors. Math Biosci 47:55–77zbMATHCrossRefGoogle Scholar
  4. 4.
    Moolgavkar S, Knudson A (1981) Mutation and cancer: a model for human carcinogenesis. J Natl Cancer Inst 66:1037–1052Google Scholar
  5. 5.
    Jacob V, Jacob P (2004) Modelling of carcinogenesis and low-dose hypersensitivity: an application to lung cancer incidence among atomic bomb survivors. Radiat Environ Biophys 42:265–273CrossRefGoogle Scholar
  6. 6.
    Coates PJ, Lorimore SA, Wright EG (2004) Damaging and protective cell signalling in the untargeted effects of ionizing radiation. Mutat Res 568:5–20Google Scholar
  7. 7.
    Nagasawa H, Little B (1999) Unexpected sensitivity to the induction of mutations by very low doses of alpha particle radiation: evidence for a bystander effect. Radiat Res 54:552–557CrossRefGoogle Scholar
  8. 8.
    Zhou HG, Randers-Pehrson G, Waldren CA, Vannais D, Hall EJ, Hei TK (2000) Induction of a bystander mutagenic effect of alpha particles in mamalian cells. Proc Natl Acad Sci 97:2099–2104CrossRefADSGoogle Scholar
  9. 9.
    Koshurnikova NA, Bolotnikova MG, Ilyin LA, Keirim-Markus IB, Menshikh ZS, Okatenko PV, Romanov SA, Tcvetkov VI, Shilnikova NS (1998) Lung cancer risk due to exposure to incorporated plutonium. Radiat Res 149:366–371CrossRefGoogle Scholar
  10. 10.
    Kreisheimer M, Sokolnikov ME, Koshurnikova NA, Khokhryakov VF, Romanow SA, Shilnikova NS, Okatenko PV, Nekolla EA, Kellerer AM (2003) Lung cancer mortality among nuclear workers of the Mayak facilities in the former Soviet Union. Radiat Environ Biophys 42:129–135CrossRefGoogle Scholar
  11. 11.
    Gilbert ES, Koshurnikova NA, Sokolnikov ME, Shilnikova NS, Preston DL, Ron E, Okatenko PV, Khokhryakov VF, Vasilenko EK, Miller S, Eckerman K, Romanov SA (2004) Lung cancer in Mayak workers. Radiat Res 162:505–515CrossRefGoogle Scholar
  12. 12.
    Jacob V, Jacob P, Meckbach R, Romanov SA, Vasilenko EK (2005) Lung cancer in Mayak workers: interaction of smoking and plutonium exposure. Radiat Environ Biophys 44:119–129CrossRefGoogle Scholar
  13. 13.
    Jacob V, Jacob P, Meckbach R, Romanov SA, Vasilenko EK (2006) Lung cancer in Mayak workers: interaction of smoking and plutonium exposure. Radiat Environ Biophys 44:307 (Erratum)CrossRefGoogle Scholar
  14. 14.
    Walsh L (2007) A short review of model selection techniques for radiation epidemiology. Radiat Environ Biophys. doi: 10.1007/s00411–007–0109–0
  15. 15.
    ICRP Publication 66 (1994) Human respiratory tract model for radiological protection. Ann ICRP 24(1–3):1–482Google Scholar
  16. 16.
    Khokhryakov VF, Suslova KG, Vostrotin VV, Romanov SA, Eckerman KF, Krahenbuhl MP, Miller SC (2005) Adaptation of the ICRP publication 66 respiratory tract model to data on plutonium biokinetics for Mayak workers. Health Phys 2:125–132CrossRefGoogle Scholar
  17. 17.
    ICRP Publication 67 (1994) Age-dependent doses to members of the public from intake of radionuclides: Part 2. Ingestion dose coefficients. Ann ICRP 23(3–4):1–167Google Scholar
  18. 18.
    Leggett RW, Eckerman KF, Khokhryakov VF, Suslova KG, Krahenbuhl MP, Miller SC (2005) Mayak worker study: an improved biokinetic model for reconstructing doses from internally deposited plutonium. Radiat Res 164:111–122CrossRefGoogle Scholar
  19. 19.
    Heidenreich WF, Jacob P, Paretzke HG (1997) Exact solutions of the clonal expansion model and their application to the incidence of solid tumors of atomic bomb survivors. Radiat Environ Biophys 36:45–58CrossRefGoogle Scholar
  20. 20.
    Akaike H (1973) Information theory and an extension of the maximum likelihood principle. In: Petrov and BN, Caski F (eds) Proceedings of the 2nd international symposium on information theory. Budapest, Hungary, Akademiai Kiado, pp 267–281Google Scholar
  21. 21.
    Schwarz G (1978) Estimating the dimension of a model. Ann Stat 6:461–464zbMATHGoogle Scholar
  22. 22.
    Luebeck AG, Heidenreich WF, Hazelton WD, Paretzke HG, Moolgavkar SH (1999) Biologically based analysis of the data for the Colorado uranium miners cohort: age, dose and dose-rate effects. Radiat Res 152:339–351CrossRefGoogle Scholar
  23. 23.
    Jacob P, Walsh L, Eidemüller M (2007) Modelling of carcinogenesis and cell killing in the atomic bomb survivors with applications to the mortality from all solid, stomach and liver cancers. (submitted)Google Scholar
  24. 24.
    ICRP Publication 60 (1992) 1990 Recommendations of the international commission on radiological protection. Ann ICRP 21(1–3):1–201Google Scholar
  25. 25.
    Jacob P, Jacob V (2003) Biological parameters for lung cancer in mathematical models of carcinogenesis. Radiat Prot Dosim 104:357–366Google Scholar
  26. 26.
    Wistuba II, Behrens C, Virmani AK, Mele G, Milchgrub S, Girard L, Fondon JW, Garner HR, McKay B, Latif F, Lerman MI, Lam S, Gazdar AF, Minna JD (2000) High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints. Cancer Res 60:1949–1960Google Scholar
  27. 27.
    Kopp-Schneider A, Haertel T, Burkolder I, Bannasch P, Wesch H, Groos J, Heeger S (2006) Investigating the formation and growth of α-particle radiation-induced foci of altered hepatocytes: a model-based approach. Radiat Res 166:422–430CrossRefGoogle Scholar
  28. 28.
    Sokolnikov ME, Khokhryakov VF, Vasilenko EK, Koshournikova NA (2003) Risk of lung cancer development in the personnel exposed to internal radiation as a result of incorporated Pu. Sibirian Med J 5:31–35 (in Russian)Google Scholar
  29. 29.
    Darby S, Hill D, Auvinen A, Barros-Dios JM, Baysson H, Bochicchio F, Deo H, Falk R, Forastiere F, Hakama M, Heid I, Kreienbrock L, Kreuzer M, Lagarde FC, Mäkeläinen I, Muirhead C, Oberaigner W, Pershagen G, Ruano-Ravina A, Ruosteenoja E, Schaffrath RA, Tirmarche MA, Tomášek L, Whitley E, Wichmann HE (2005) Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies. BMJ 330:223–226CrossRefGoogle Scholar
  30. 30.
    Preston DL, Shimizu Y, Pierce DA, Suyama A, Mabuchi K (2003) Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and non-cancer disease mortality: 1950–1997. Radiat Res 160:381–407CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • P. Jacob
    • 1
    Email author
  • R. Meckbach
    • 1
  • M. Sokolnikov
    • 2
  • V. V. Khokhryakov
    • 2
  • E. Vasilenko
    • 3
  1. 1.GSF National Research Center for Environment and HealthInstitute of Radiation ProtectionNeuherbergGermany
  2. 2.Southern Urals Biophysics InstituteOzyorskRussia
  3. 3.Mayak Production AssociationOzyorskRussia

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