Abstract
Aims: In occupational settings, carcinogenic exposures are often repeated or protracted over time. The time pattern of exposure accrual may influence subsequent temporal patterns of cancer risk. The authors present several simple models that may be used to evaluate the influence of time since exposure or age at exposure on cancer incidence or mortality in an occupational cohort.
Methods: A cohort of 40 415 nuclear industry workers was identified via the Canadian National Dose Registry. Vital status and cause of death were ascertained through 1994. Associations between ionising radiation and mortality due to lung cancer, leukaemia, and cancers other than lung and leukaemia were quantified using conditional logistic regression models with risk sets constructed by incidence density sampling. A step function, a bilinear function, and a sigmoid function were used to evaluate temporal variation in exposure effects.
Results: Step and sigmoid functions were used to explore latency and morbidity periods. For analyses of lung cancer, leukaemia, and other cancers the best fitting models were obtained when exposure assignment was lagged by 13, 0, and 5 years, respectively. A bilinear function was used to evaluate whether exposure effects diminished with time since exposure. In analyses of lung cancer and leukaemia, there was evidence that radiation effects attenuated with protracted time since exposure. In analyses of age at exposure, there was evidence of variation in radiation mortality associations for analyses of lung cancer and leukaemia; discounting radiation doses accrued at younger ages (for example, 15–35 years) led to significant improvements in model fit.
Conclusions: This paper illustrates empirical approaches to evaluating temporal variation in the effect of a protracted exposure on disease risk.
Full Text
The Full Text of this article is available as a PDF (125.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ashmore J. P., Krewski D., Zielinski J. M., Jiang H., Semenciw R., Band P. R. First analysis of mortality and occupational radiation exposure based on the National Dose Registry of Canada. Am J Epidemiol. 1998 Sep 15;148(6):564–574. doi: 10.1093/oxfordjournals.aje.a009682. [DOI] [PubMed] [Google Scholar]
- Cardis E., Gilbert E. S., Carpenter L., Howe G., Kato I., Armstrong B. K., Beral V., Cowper G., Douglas A., Fix J. Effects of low doses and low dose rates of external ionizing radiation: cancer mortality among nuclear industry workers in three countries. Radiat Res. 1995 May;142(2):117–132. [PubMed] [Google Scholar]
- Checkoway H., Pearce N., Hickey J. L., Dement J. M. Latency analysis in occupational epidemiology. Arch Environ Health. 1990 Mar-Apr;45(2):95–100. doi: 10.1080/00039896.1990.9935932. [DOI] [PubMed] [Google Scholar]
- Checkoway H., Rice C. H. Time-weighted averages, peaks, and other indices of exposure in occupational epidemiology. Am J Ind Med. 1992;21(1):25–33. doi: 10.1002/ajim.4700210106. [DOI] [PubMed] [Google Scholar]
- Darby S. C., Nakashima E., Kato H. A parallel analysis of cancer mortality among atomic bomb survivors and patients with ankylosing spondylitis given X-ray therapy. J Natl Cancer Inst. 1985 Jul;75(1):1–21. [PubMed] [Google Scholar]
- Frome E. L., Cragle D. L., Watkins J. P., Wing S., Shy C. M., Tankersley W. G., West C. M. A mortality study of employees of the nuclear industry in Oak Ridge, Tennessee. Radiat Res. 1997 Jul;148(1):64–80. [PubMed] [Google Scholar]
- Gribbin M. A., Weeks J. L., Howe G. R. Cancer mortality (1956-1985) among male employees of Atomic Energy of Canada Limited with respect to occupational exposure to external low-linear-energy-transfer ionizing radiation. Radiat Res. 1993 Mar;133(3):375–380. [PubMed] [Google Scholar]
- Hauptmann M., Berhane K., Langholz B., Lubin J. Using splines to analyse latency in the Colorado Plateau uranium miners cohort. J Epidemiol Biostat. 2001;6(6):417–424. doi: 10.1080/135952201317225444. [DOI] [PubMed] [Google Scholar]
- Hauptmann M., Wellmann J., Lubin J. H., Rosenberg P. S., Kreienbrock L. Analysis of exposure-time-response relationships using a spline weight function. Biometrics. 2000 Dec;56(4):1105–1108. doi: 10.1111/j.0006-341x.2000.01105.x. [DOI] [PubMed] [Google Scholar]
- Howe G. R. Use of computerized record linkage in cohort studies. Epidemiol Rev. 1998;20(1):112–121. doi: 10.1093/oxfordjournals.epirev.a017966. [DOI] [PubMed] [Google Scholar]
- Kneale G. W., Stewart A. M. Factors affecting recognition of cancer risks of nuclear workers. Occup Environ Med. 1995 Aug;52(8):515–523. doi: 10.1136/oem.52.8.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Langholz B., Thomas D., Xiang A., Stram D. Latency analysis in epidemiologic studies of occupational exposures: application to the Colorado Plateau uranium miners cohort. Am J Ind Med. 1999 Mar;35(3):246–256. doi: 10.1002/(sici)1097-0274(199903)35:3<246::aid-ajim4>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
- Pearce N. Methodological problems of time-related variables in occupational cohort studies. Rev Epidemiol Sante Publique. 1992;40 (Suppl 1):S43–S54. [PubMed] [Google Scholar]
- Pierce Donald A. Age-time patterns of radiogenic cancer risk: their nature and likely explanations. J Radiol Prot. 2002 Sep;22(3A):A147–A154. doi: 10.1088/0952-4746/22/3a/326. [DOI] [PubMed] [Google Scholar]
- Pierce Donald A., Sharp Gerald B., Mabuchi Kiyohiko. Joint effects of radiation and smoking on lung cancer risk among atomic bomb survivors. Radiat Res. 2003 Apr;159(4):511–520. doi: 10.1667/0033-7587(2003)159[0511:jeoras]2.0.co;2. [DOI] [PubMed] [Google Scholar]
- Richardson D. B., Wing S. Greater sensitivity to ionizing radiation at older age: follow-up of workers at Oak Ridge National Laboratory through 1990. Int J Epidemiol. 1999 Jun;28(3):428–436. doi: 10.1093/ije/28.3.428. [DOI] [PubMed] [Google Scholar]
- Richardson D. B., Wing S., Hoffmann W. Cancer risk from low-level ionizing radiation: the role of age at exposure. Occup Med. 2001 Apr-Jun;16(2):191–218. [PubMed] [Google Scholar]
- Richardson D. B., Wing S. Radiation and mortality of workers at Oak Ridge National Laboratory: positive associations for doses received at older ages. Environ Health Perspect. 1999 Aug;107(8):649–656. doi: 10.1289/ehp.99107649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ritz B., Morgenstern H., Moncau J. Age at exposure modifies the effects of low-level ionizing radiation on cancer mortality in an occupational cohort. Epidemiology. 1999 Mar;10(2):135–140. [PubMed] [Google Scholar]
- Ritz B. Radiation exposure and cancer mortality in uranium processing workers. Epidemiology. 1999 Sep;10(5):531–538. [PubMed] [Google Scholar]
- Robins J. M., Gail M. H., Lubin J. H. More on "Biased selection of controls for case-control analyses of cohort studies". Biometrics. 1986 Jun;42(2):293–299. [PubMed] [Google Scholar]
- Rothman K. J. Induction and latent periods. Am J Epidemiol. 1981 Aug;114(2):253–259. doi: 10.1093/oxfordjournals.aje.a113189. [DOI] [PubMed] [Google Scholar]
- Salvan A., Stayner L., Steenland K., Smith R. Selecting an exposure lag period. Epidemiology. 1995 Jul;6(4):387–390. doi: 10.1097/00001648-199507000-00010. [DOI] [PubMed] [Google Scholar]
- Sont W. N., Zielinski J. M., Ashmore J. P., Jiang H., Krewski D., Fair M. E., Band P. R., Létourneau E. G. First analysis of cancer incidence and occupational radiation exposure based on the National Dose Registry of Canada. Am J Epidemiol. 2001 Feb 15;153(4):309–318. doi: 10.1093/aje/153.4.309. [DOI] [PubMed] [Google Scholar]
- Thierry-Chef I., Pernicka F., Marshall M., Cardis E., Andreo P. Study of a selection of 10 historical types of dosemeter: variation of the response to Hp(10) with photon energy and geometry of exposure. Radiat Prot Dosimetry. 2002;102(2):101–113. doi: 10.1093/oxfordjournals.rpd.a006078. [DOI] [PubMed] [Google Scholar]
- Weiss H. A., Darby S. C., Doll R. Cancer mortality following X-ray treatment for ankylosing spondylitis. Int J Cancer. 1994 Nov 1;59(3):327–338. doi: 10.1002/ijc.2910590307. [DOI] [PubMed] [Google Scholar]
- Weiss H. A., Darby S. C., Fearn T., Doll R. Leukemia mortality after X-ray treatment for ankylosing spondylitis. Radiat Res. 1995 Apr;142(1):1–11. [PubMed] [Google Scholar]