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

Area of Science:

• Toxicology
• Carcinogenesis Research
• Statistical Modeling in Biology

Background:

• Rodent body weight is often linked to tumor incidence at various sites.
• Chemical carcinogenicity studies frequently involve chemicals that alter animal body weight.
• Discrepancies in body weight across dose groups can introduce bias in tumor incidence comparisons.

Purpose of the Study:

• To investigate a method for reducing bias in tumor incidence comparisons caused by body weight differences.
• To assess the impact of chemical-induced body weight changes on carcinogenicity bioassay results.

Main Methods:

• Animals were divided into groups based on body weight at 12 months, prior to tumor manifestation.
• Dose-response trend tests for tumor incidence were calculated within these body weight strata.
• Stratified statistics were pooled to determine an overall dose-response trend.

Main Results:

• Analysis within body weight strata revealed positive dose-response trends for tumor incidence in several cases.
• Weight-adjusted analysis identified a genuine negative dose-response trend in one instance, distinct from body weight reduction.
• Even minor body weight changes (around 10%) caused by chemicals can significantly impact 2-year carcinogenicity bioassay outcomes.

Conclusions:

• Stratifying by body weight is a crucial adjustment for accurate interpretation of tumor incidence in carcinogenicity studies.
• This method effectively mitigates bias stemming from dose group body weight variations.
• Researchers must consider body weight alterations, even subtle ones, when evaluating chemical carcinogenicity.