Age-adjustment in experimental animal data and its application to lung cancer in radon-exposed rats

• Published in: Radiation and environmental biophysics 2004-09, Vol.43 (3), p.183-188
• Main Authors: Heidenreich, W F, Collier, C, Morlier, J P, Cross, F T, Kaiser, J C, Monchaux, G
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Age Factors; Aging; Air Pollutants, Radioactive - adverse effects; Algorithms; Animals; Cancer; Clinical trials; Computer Simulation; Disease Models, Animal; Exposure; Female; Incidence; Life Sciences; Lung cancer; Lung Neoplasms - etiology; Male; Models, Biological; Neoplasms, Experimental - etiology; Neoplasms, Radiation-Induced - etiology; Radon; Radon - administration & dosage; Radon - adverse effects; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reproducibility of Results; Risk Assessment - methods; Risk Factors; Rodents; Sensitivity and Specificity; Survival Analysis; Young adults
• ISSN: 0301-634X; 1432-2099
• DOI: 10.1007/s00411-004-0250-y

Procedures for age-adjustment of cancer fractions are proposed which do not require fixed age intervals. The full available information on survival times can then be used, which is especially important in small treatment groups. For incidental cancers a non-decreasing prevalence function and for fatal cancers the Kaplan-Meier estimator is used. In the latter case, the estimated competing risk of the control population is standardized, not its true survival. This makes the technique also applicable to treatment groups with high incidence, which otherwise may give adjusted rates above 100%. In the application part these age-adjustment techniques are used here to study lung cancer in radon-exposed Wistar and Sprague-Dawley rats. The data include a classification in fatal and incidental lung cancers. For fatal lung cancer, the lifetime excess absolute risk (LEAR) at 1 WLM averaged over all exposed groups is 0.67x10(-4) for the Wistar rats, while for the Sprague-Dawley rats it is 0.40x10(-4). For the Sprague-Dawley rats, there are several groups exposed later in life. When the averaging is restricted to animals with start of exposure prior to 150 days of age, the weighted average risk among the Sprague-Dawley rats is 0.79x10(-4). Compared to groups with similar exposures as young adults (up to about 150 days), animals exposed later in life have substantially lower lifetime risks. The Wistar rats include groups with roughly equal exposure rates and ages at start of exposure, but with increasing exposure duration. Within these groupings the LEAR at 1 WLM does not decrease with additional exposure at higher age, as would be expected if the risk from exposures at different ages would be additive.