Radiation and Environmental Biophysics

, Volume 53, Issue 3, pp 505–513 | Cite as

Kidney cancer mortality and ionizing radiation among French and German uranium miners

  • Damien DrubayEmail author
  • Sophie Ancelet
  • Alain Acker
  • Michaela Kreuzer
  • Dominique Laurier
  • Estelle Rage
Original Paper


The investigation of potential adverse health effects of occupational exposures to ionizing radiation, on uranium miners, is an important area of research. Radon is a well-known carcinogen for lung, but the link between radiation exposure and other diseases remains controversial, particularly for kidney cancer. The aims of this study were therefore to perform external kidney cancer mortality analyses and to assess the relationship between occupational radiation exposure and kidney cancer mortality, using competing risks methodology, from two uranium miners cohorts. The French (n = 3,377) and German (n = 58,986) cohorts of uranium miners included 11 and 174 deaths from kidney cancer. For each cohort, the excess of kidney cancer mortality has been assessed by standardized mortality ratio (SMR) corrected for the probability of known causes of death. The associations between cumulative occupational radiation exposures (radon, external gamma radiation and long-lived radionuclides) or kidney equivalent doses and both the cause-specific hazard and the probability of occurrence of kidney cancer death have been estimated with Cox and Fine and Gray models adjusted to date of birth and considering the attained age as the timescale. No significant excess of kidney cancer mortality has been observed neither in the French cohort (SMR = 1.49, 95 % confidence interval [0.73; 2.67]) nor in the German cohort (SMR = 0.91 [0.77; 1.06]). Moreover, no significant association between kidney cancer mortality and any type of occupational radiation exposure or kidney equivalent dose has been observed. Future analyses based on further follow-up updates and/or large pooled cohorts should allow us to confirm or not the absence of association.


Kidney cancer mortality Ionizing radiation Uranium miners Competing risks 



This work was partly supported by AREVA NC, in the framework of a bilateral IRSN-AREVA-NC research agreement, and by the European Commission through the DoReMI program (low Dose Research toward Multidisciplinary Integration). The authors thank Florian Dufey for his valuable contribution.


  1. Allodji RS, Leuraud K, Bernhard S, Henry S, Benichou J, Laurier D (2012) Assessment of uncertainty associated with measuring exposure to radon and decay products in the French uranium miners cohort. J Radiol Prot 32(1):85–100CrossRefGoogle Scholar
  2. Boice JD Jr, 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, Coleman MP, Fraser P, Neal FE, Prior P, Choi NW, Hislop TG, Koch M, Kreiger N, Robb D, Robson D, Thomson DH, Lochmüller H, von Fournier D, Frischkorn R, Kjørstad KE, Rimpela A, Pejovic MH, Pompe-Kirn V, Stankusova H, Berrino F, Sigurdsson K, Hutchison GB, MacMahon B (1988) Radiation dose and second cancer risk in patients treated for cancer of the cervix. Radiat Res 116(1):3–55CrossRefGoogle Scholar
  3. Breslow NE, Day NE (1987) Statistical methods in cancer research. Volume II—The design and analysis of cohort studies. IARC Sci Publ 82:1–406Google Scholar
  4. Cologne J, Hsu WL, Abbott RD, Ohishi W, Grant EJ, Fujiwara S, Cullings HM (2012) Proportional hazards regression in epidemiologic follow-up studies: an intuitive consideration of primary time scale. Epidemiology 23(4):565–573CrossRefGoogle Scholar
  5. Cox DR (1975) Partial likelihood. Biometrika 62(2):269–276CrossRefzbMATHMathSciNetGoogle Scholar
  6. Cross FT, Buschbom RL, Dagle GE, Gideon KM, Gies RA, Gilbert ES (1990) Inhalation hazards to uranium miners. Technical Report Part 1: biomedical sciences, Pacific Northwest Laboratory annual report for 1989 to the DOE Office of Energy Research, PNL-7200. Pacific Northwest Laboratory, Richland, WAGoogle Scholar
  7. Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRefzbMATHMathSciNetGoogle Scholar
  8. Geskus RB (2011) Cause-specific cumulative incidence estimation and the fine and gray model under both left truncation and right censoring. Biometrics 67(1):39–49CrossRefzbMATHMathSciNetGoogle Scholar
  9. Grambsch PM, Therneau TM (1994) Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 81:515–526CrossRefzbMATHMathSciNetGoogle Scholar
  10. Gueguen Y, Rouas C (2012) Données nouvelles sur la nephrotoxicité de l’uranium. Radioprotection 47(3):345–359CrossRefGoogle Scholar
  11. Howe CJ, Cole SR, Chmiel JS, Munoz A (2011) Limitation of inverse probability-of-censoring weights in estimating survival in the presence of strong selection bias. Am J Epidemiol 173(5):569–577CrossRefGoogle Scholar
  12. International Commission in Radiological Protection (2007) The 2007 Recommendations of the international commission on radiological protection. ICRP publication 103 Ann ICRP 37 (2–4):1–332Google Scholar
  13. Kendall GM, Smith TJ (2002) Doses to organs and tissues from radon and its decay products. J Radiol Prot 22(4):389–406CrossRefGoogle Scholar
  14. Koller MT, Raatz H, Steyerberg EW, Wolbers M (2012) Competing risks and the clinical community: irrelevance or ignorance? Stat Med 31(11–12):1089–1097CrossRefMathSciNetGoogle Scholar
  15. Kreuzer M, Walsh L, Schnelzer M, Tschense A, Grosche B (2008) Radon and risk of extrapulmonary cancers: results of the German uranium miners’ cohort study, 1960–2003. Br J Cancer 99(11):1946–1953CrossRefGoogle Scholar
  16. Kreuzer M, Grosche B, Schnelzer M, Tschense A, Dufey F, Walsh L (2010a) Radon and risk of death from cancer and cardiovascular diseases in the German uranium miners cohort study: follow-up 1946–2003. Radiat Environ Biophys 49(2):177–185CrossRefGoogle Scholar
  17. Kreuzer M, Schnelzer M, Tschense A, Walsh L, Grosche B (2010b) Cohort profile: the German uranium miners cohort study (WISMUT cohort), 1946–2003. Int J Epidemiol 39(4):980–987CrossRefGoogle Scholar
  18. Kulich M, Rericha V, Rericha R, Shore DL, Sandler DP (2011) Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study. Environ Res 111(3):400–405CrossRefGoogle Scholar
  19. Kurttio P, Salonen L, Ilus T, Pekkanen J, Pukkala E, Auvinen A (2006) Well water radioactivity and risk of cancers of the urinary organs. Environ Res 102(3):333–338CrossRefGoogle Scholar
  20. Latouche A, Allignol A, Beyersmann J, Labopin M, Fine JP (2013) A competing risks analysis should report results on all cause-specific hazards and cumulative incidence functions. J Clin Epidemiol 66(6):648–653CrossRefGoogle Scholar
  21. Lau B, Cole SR, Gange SJ (2009) Competing risk regression models for epidemiologic data. Am J Epidemiol 170(2):244–256CrossRefGoogle Scholar
  22. Laurent O, Metz-Flamant C, Rogel A, Hubert D, Riedel A, Garcier Y, Laurier D (2010) Relationship between occupational exposure to ionizing radiation and mortality at the French electricity company, period 1961–2003. Int Arch Occup Environ Health 83(8):935–944CrossRefGoogle Scholar
  23. Lehmann F (2004) Job-exposure-matrix ionisierende strahlung im uranerzbergbau der ehemaligen ddr [version 06/2003]. Technical report, Bergbau BG, GeraGoogle Scholar
  24. Ljungberg B, Campbell SC, Choi HY, Jacqmin D, Lee JE, Weikert S, Kiemeney LA (2011) The epidemiology of renal cell carcinoma. Eur Urol 60(4):615–621CrossRefGoogle Scholar
  25. Maraninchi D, Cerf N, Bousquet P (2010) Dynamique d’évolution des taux de mortalité des principaux cancers en France. Institut national du cancer (INCa), Boulogne-BillancourtGoogle Scholar
  26. Marsh JW, Bessa Y, Birchall A, Blanchardon E, Hofmann W, Nosske D, Tomasek L (2008) Dosimetric models used in the alpha-risk project to quantify exposure of uranium miners to radon gas and its progeny. Radiat Prot Dosimetry 130(1):101–106CrossRefGoogle Scholar
  27. Marsh JW, Blanchardon E, Gregoratto D, Hofmann W, Karcher K, Nosske D, Tomasek L (2012) Dosimetric calculations for uranium miners for epidemiological studies. Radiat Prot Dosimetry 149(4):371–383CrossRefGoogle Scholar
  28. Masse R, Morlier JP, Morin M, Chameaud J, Bredon P, Lafuma J (1992) Animals exposed to radon. Radiat Prot Dosimetry 45:603–610Google Scholar
  29. Muirhead CR, Goodill AA, Haylock RG, Vokes J, Little MP, Jackson DA, O’Hagan JA, Thomas JM, Kendall GM, Silk TJ, Bingham D, Berridge GL (1999) Occupational radiation exposure and mortality: second analysis of the national registry for radiation workers. J Radiol Prot 19(1):3–26CrossRefGoogle Scholar
  30. Navai N, Wood CG (2012) Environmental and modifiable risk factors in renal cell carcinoma. Urol Oncol 30(2):220–224CrossRefGoogle Scholar
  31. NRC (2006) Committee to assess health risks from exposure to low levels of ionizing radiation, national research council (NRC). Health risks from exposure to low levels of ionizing radiation: BEIR VII—Phase 2. National Academy of Sciences, Washington, DCGoogle Scholar
  32. Ozasa K, Shimizu Y, Suyama A, Kasagi F, Soda M, Grant EJ, Sakata R, Sugiyama H, Kodama K (2012) Studies of the mortality of atomic bomb survivors, Report 14, 1950–2003: an overview of cancer and noncancer diseases. Radiat Res 177(3):229–243CrossRefGoogle Scholar
  33. Pepe MS, Mori M (1993) Kaplan-Meier, marginal or conditional probability curves in summarizing competing risks failure time data? Stat Med 12(8):737–751CrossRefGoogle Scholar
  34. Putter H, Fiocco M, Geskus RB (2007) Tutorial in biostatistics: competing risks and multi-state models. Stat Med 26(11):2389–2430CrossRefMathSciNetGoogle Scholar
  35. Richardson DB, Hamra G (2010) Ionizing radiation and kidney cancer among Japanese atomic bomb survivors. Radiat Res 173(6):837–842CrossRefGoogle Scholar
  36. Rittgen W, Becker N (2000) SMR analysis of historical follow-up studies with missing death certificates. Biometrics 56(4):1164–1169CrossRefzbMATHMathSciNetGoogle Scholar
  37. Runge W (1999) Chronik der Wismut. Technical report. Wismut GmbH (2738 pages, in German)Google Scholar
  38. Therneau TM, Grambsch PM (2000) Modeling survival data: extending the cox model. Springer, New YorkCrossRefGoogle Scholar
  39. UNSCEAR (2006) Report of the United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2006 Report. Volume 1. Annex A: epidemiological studies of radiation and cancer. United Nations Scientific Committee on the Effects of Atomic Radiation, New YorkGoogle Scholar
  40. Vacquier B, Caer S, Rogel A, Feurprier M, Tirmarche M, Luccioni C, Quesne B, Acker A, Laurier D (2008) Mortality risk in the French cohort of uranium miners: extended follow-up 1946–1999. Occup Environ Med 65(9):597–604CrossRefGoogle Scholar
  41. Vacquier B, Rogel A, Leuraud K, Caer S, Acker A, Laurier D (2009) Radon-associated lung cancer risk among French uranium miners: modifying factors of the exposure-risk relationship. Radiat Environ Biophys 48(1):1–9CrossRefGoogle Scholar
  42. Vacquier B, Rage E, Leuraud K, Caer-Lorho S, Houot J, Acker A, Laurier D (2011) The influence of multiple types of occupational exposure to radon, gamma rays and long-lived radionuclides on mortality risk in the French “post-55” sub-cohort of uranium miners: 1956-1999. Radiat Res 176(6):796–806CrossRefGoogle Scholar
  43. Vicente L, Quiros Y, Perez-Barriocanal F, Lopez-Novoa JM, Lopez-Hernandez FJ, Morales AI (2010) Nephrotoxicity of uranium: pathophysiological, diagnostic and therapeutic perspectives. Toxicol Sci 118(2):324–347CrossRefGoogle Scholar
  44. Walsh L, Dufey F, Mohner M, Schnelzer M, Tschense A, Kreuzer M (2011) Differences in baseline lung cancer mortality between the German uranium miners cohort and the population of the former German Democratic Republic (1960–2003). Radiat Environ Biophys 50(1):57–66CrossRefGoogle Scholar
  45. Weiss HA, Darby SC, Doll R (1994) Cancer mortality following X-ray treatment for ankylosing spondylitis. Int J Cancer 59(3):327–338CrossRefGoogle Scholar
  46. Wilson EB (1927) Probable inference, the law of succession, and statistical inference. J Am Stat Assoc 22:209–212CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Damien Drubay
    • 1
    Email author
  • Sophie Ancelet
    • 1
  • Alain Acker
    • 2
  • Michaela Kreuzer
    • 3
  • Dominique Laurier
    • 1
  • Estelle Rage
    • 1
  1. 1.Laboratory of EpidemiologyInstitut de Radioprotection et de Sûreté Nucléaire (IRSN)Fontenay-aux-Roses cedexFrance
  2. 2.AREVA NCParisFrance
  3. 3.Department of Radiation Protection and HealthFederal Office for Radiation Protection and HealthNeuherbergGermany

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