Dose-response trend tests for tumorigenesis, adjusted for body weight

Citation
Dw. Gaylor et Rl. Kodell, Dose-response trend tests for tumorigenesis, adjusted for body weight, TOXICOL SCI, 49(2), 1999, pp. 318-323
Citations number
10
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGICAL SCIENCES
ISSN journal
10966080 → ACNP
Volume
49
Issue
2
Year of publication
1999
Pages
318 - 323
Database
ISI
SICI code
1096-6080(199906)49:2<318:DTTFTA>2.0.ZU;2-D
Abstract
Several studies have demonstrated a relationship between rodent body weight and tumor incidence for some tissue/organ sites. It is not uncommon for a chemical tested for carcinogenicity to also affect body weight. In such cas es, comparisons of tumor incidence may be biased by body-weight differences across dose groups. A simple procedure was investigated for reducing this bias. This procedure divides the animals into a few groups based on body we ight. Body weight at 12 months was used, before the appearance of a tumor w as likely to affect body weight. Statistics for dose-response trend tests a re calculated within body weight strata and pooled to obtain an overall dos e-response trend test. This procedure is analogous to that currently used, of stratifying animals, based on their age at the time of removal from a st udy. Age stratification is used to account for differences in animal age ac ross dose groups, which can affect comparisons of tumor incidence. Several examples were investigated where the high-dose group had reduced body weigh ts and associated reductions in tumor incidence, When the data were analyze d by body-weight strata, some positive dose-response trends for tumor incid ence were demonstrated. In one case, the weight-adjusted analysis indicated that a negative dose-response trend in tumor incidence was a real effect, in addition to a body weight reduction. These examples indicate that it is important to consider the effects of body weight changes as low as 10%, and perhaps below, that were caused by chemicals in 2-year bioassays for carci nogenesis. The simple procedure of analyzing tumor incidence within bodywei ght strata can reduce the bias introduced by weight differences across dose groups.