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- [Aspirin] shows the effect of aspirin on intestinal tumors in rats and mice (2 tables, 4 figures)
- [Calcium] shows the effect of calcium on intestinal tumors in rats and mice (2 tables, 6 figures)
- [Wheat Bran] shows the effect of wheat bran on intestinal tumors in rats and mice (2 tables, 6 figures)
- [Beta-Carotene] shows the effect of carotene on tumors in rodents (1 table, 2 fig. No Min mouse study)To quote the Meta-Analysis, cite: Corpet D.E. & Pierre F., 2005, European Journal of Cancer, 41: 1911-1922.
How good are Rodent Models of Carcinogenesis in Predicting Efficacy in Humans? Systematic Review and Meta-Analysis of Colon Tumour Chemoprevention in Rats, Mice and Men. [EJC reprint].pdf
EJC article major figure, comparing chemoprevention in men & rats,Abstract: To know if rodent models of colon carcinogenesis are good predictors of chemopreventive efficacy in humans, we made a meta-analysis of aspirin, beta-carotene, calcium, and wheat bran studies. Controlled intervention studies of adenoma recurrence in human volunteers were compared with chemoprevention studies of carcinogen-induced tumours in rats, and of polyps in Min (Apc(+/-)) mice: 6714 volunteers, 3911 rats and 458 mice were included in the meta-analyses. Difference between models was small since most global relative risks were between 0.76 and 1.00. A closer look showed that carcinogen-induced rat studies matched human trials for aspirin, calcium, carotene, and were compatible for wheat bran. Min mice results were compatible with human results for aspirin, but discordant for calcium and wheat bran (no carotene study). These few results suggest that rodent models roughly predict effect in humans, but the prediction is not accurate for all agents. Based on three cases only, the carcinogen-induced rat model seems better than the Min mouse model. However, rodent studies are useful to screen potential chemopreventive agents, and to study mechanisms of carcinogenesis and chemoprevention.
or men & mice: screen size or full size
Abbreviations in Data Tables - Meta-Analysis Methods
- Meta-Analysis Software:
Meta-Analysis sharewares EasyMA DOS (2001 version) and EasyMA online (2005 version) were used to analyse rats and mice data, respectively.
- Column "p": NS, Non Significant; MS, Marginally Significant; *, significant: p<0.05 (by Fisher's test).
Last line: Meta-analysis global p value, calculated by Chi-square test, without Yates correction for continuity.
RR and p values calculated with Random Effect Model are shown at the bottom of the figures
- Columns 3 & 4: Number of tumor-bearing rats in control group (col.3); Total number of control rats (col.4).
Control rats' data were duplicated in each line with treated rats data, although control rats were summed only once in last line. When a single group of control rats was reported in several rows, duplicated data were tagged with a "-" (e.g., 15- )
- Meta-Analysis Methods, Rats:
The meta-analysis of carcinogen-injected rats was done as follows: we searched articles on Medline/PubMed database and in "references" sections (cut-off date, January 2005). Some papers were not included because not in English, poor protocol, missing or aberrant data (list given (excluded calcium refs) and (excluded w. bran refs)).
Studies were far from homogeneity (all Q Cochran's p<0.01), which disqualified Fixed effects model. "Random Effects" model was used to calculate common RR, 95% confidence intervals and p values which are shown in Figures above.
Funnel plots were drawn to detect publication bias, which were tested by rank test. However, the Random model calculation needed to duplicate control data, because many studies use a single control group for several treated groups. Each control rat was thus included several times in the table, which should not be.
We thus used also another approach:
Raw number of tumour-bearing rats, and of tumour-free rats, in control and treated groups, were included in a table, and summed up as if all rats had been treated in a single study (each control rat was included only once, see Tables). The 2x2 contingency table with all rats was then analysed with Chi-square statistics (without Yates correction), and 95% confidence intervals (CI) were calculated and shown in last line of Tables (links above). This option of pooling data from all studies was chosen, including rats and mice, initiated by various carcinogens, and treated with various doses. We reasoned that when a human population is treated with a chemopreventive agent, people are exposed to various carcinogens, and have different genetic backgrounds and different diets. We thus had no a priori reason to exclude any rodent protocol.
- Meta-Analysis Methods, Mice:
The meta-analysis of Min mice intestinal polyp studies was done as follows:
Global Effect Size and p value were first calculated with "Random Effects" model and shown on Figures above. However a second approach was also used because Effect Size cannot be compared with RR
We thus chose to use ratios instead of differences. Number of adenomas per mouse in treated group was divided by corresponding value in control group and multiplied by 100, for each study. The mean of these percentages was compared with the hypothetical 100% value (H0 hypothesis) in a one sample Student t test: raw data, mean and p values are shown on Tables above, last line. Also, a weighted mean was calculated, taking in account the number of mice per study.