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Body Weight-Tumor Incidence Correlations in Long-Term Rodent Carcinogenicity Studies
Joseph K. Haseman
Statistics and Biomathematics Branch National Institute of Environmental Health Sciences
Erika Young
Statistics and Biomathematics Branch National Institute of Environmental Health Sciences
Scottie L. Eustis
Statistics and Biomathematics Branch National Institute of Environmental Health Sciences
J. Rick Hailey
Pathology Branch, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709
Associations between body weight and tumor incidence and among the incidences of selected site-specific tumors were examined for more than 4,000 male and female Fischer-344 rats and B6C3F1 mice in the National Toxicology Program historical control database. Incidences of certain site-specific tumors, most notably mammary gland and pituitary gland tumors in rats and liver tumors in mice, were shown to have a strong positive correlation with 52-wk body weight. Using individual animal data, logistic regression models were derived for predicting site-specific tumor incidence as a function of 52-wk body weight, age, and other factors. This association between body weight and tumor incidence can explain many of the decreased tumor incidences observed in National Toxicology Program carcinogenicity studies. Body weight differences between dosed and control groups can also mask carcinogenic effects for those sites sensitive to body weight changes. Thus, when designing long-term rodent carcinogenicity studies, measures should be taken to minimize potential body weight differences between dosed and control groups. There were a number of small but significant negative correlations among tumor incidences, reflecting primarily the lethality of the tumors in question. None of these correlations (nor the 2 small positive correlations found) are likely to have any impact on the interpretation of experimental results. However, the high negative correlation between pituitary gland and testis tumors in male Fischer-344 rats cannot be dismissed so easily, does not reflect tumor lethality, and is currently being studied further.
Key Words: Tumor associations • historical control data • Fischer-344 rats • B6C3F1 mice • pituitary gland tumors • interstitial cell testis tumors • logistic regression models • National Toxicology Program
Toxicologic Pathology, Vol. 25, No. 3,
256-263 (1997)
DOI: 10.1177/019262339702500302
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