Abstract 2098: The effect of in utero folic acid supplementation on colorectal cancer risk in the offspring in a chemical carcinogen rodent model
Bibliographic record
Abstract
Abstract Background: Epidemiologic studies suggest that dietary intake and blood levels of folate are inversely related to colorectal cancer (CRC) risk. However, animal studies and recent human intervention trials have suggested that although folate supplementation may decrease the risk of developing de novo CRC, folate supplementation may promote the progression of existing, undiagnosed preneoplastic lesions in the colorectum to CRC. Total intake and blood levels of folate in North America have dramatically increased over the past decade owing to mandatory folic acid (FA; the synthetic form of folate) fortification and 30-40% of the population taking multivitamins containing FA. It is unknown whether high folate in the intrauterine environment may affect CRC risk in the offspring. We therefore investigated the effect of FA supplementation provided in utero and postnatally on CRC risk in the offspring in the azoxymethane (AOM) rat model of CRC. Methods: Female Sprague-Dawley rats were placed on either a control diet (2mg FA/kg diet) or a supplemented diet (5mg FA) for 3 weeks prior to breeding, and remained on the diet throughout pregnancy and lactation. Male pups from each maternal diet group were randomized to either the control or supplemented diet (n=55 per group) at weaning (21 days of age). At 5 and 6 weeks of age, 2 weekly s.c. injections of AOM were given. At 34 weeks of age, all rats were sacrificed and tumor incidence, multiplicity and burden as well as plasma folate and homocysteine (Hcy; an accurate inverse indicator of folate status) and liver folate concentrations were determined. Results: Plasma and liver folate concentrations accurately reflected dietary FA levels (p<0.001), and a significant interaction was found between maternal and pup diets (p< 0.02). Plasma Hcy was lower in pups fed the 5mg diet (p=0.036). Maternal FA supplementation significantly decreased the risk of developing CRC in the offspring (p=0.003) whereas postnatal FA supplementation had no significant effect. Pups from dams on the control diet had a nearly 3-fold increased risk of developing CRC compared with those from dams on FA supplementation (odds ratio=2.78; 95% CI, 1.41-5.50). There was no significant effect of interaction between maternal and pup diets on CRC incidence. Total number of tumors and sum of tumor diameter were significantly different among the diet groups (p=0.014 and p=0.006, respectively) with FA supplemented pups from dams on the control diet bearing a higher number of tumors and a larger tumor diameter than other groups (p<0.03). Conclusions: Notwithstanding the limitations associated with this model, our data suggest that FA supplementation provided in utero, but not postnatally, may protect the offspring from developing CRC. Although FA supplementation may promote the progression of established precursors of CRC, FA supplementation may decrease the risk of developing de novo CRC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".