Association of Prebiotic Fiber Intake With Colorectal Cancer Risk in an Italian Case-Control Study

Abstract

INTRODUCTION
Colorectal cancer (CRC) is inversely associated with dietary fiber intake. Prebiotic fibers are a subgroup of dietary fibers defined as non-digestible compounds selectively utilized by the gut microbiota, potentially influencing intestinal homeostasis. Some prebiotics such as inulin-type fructans (ITF) and galacto-oligosaccharides (GOS) have been investigated in relation to CRC risk, but epidemiological evidence is inconsistent. A large case-control study reported inverse associations for GOS, while findings for ITF are generally null. Overall, data on specific prebiotic fibers and CRC risk remain limited.

OBJECTIVES
To investigate the association between intake of specific prebiotic fibers, including ITF, fructo-oligosaccharides (FOS) and GOS and CRC risk in an Italian case-control study.

METHODS
We analyzed data from a multicentric case-control study conducted in Milan (Italy) between 2017 and 2019, including 100 histologically confirmed CRC cases and 200 controls, of whom 100 had intestinal adenomas (IA) and 100 were IA- and cancer-free. Cases and controls were individually matched by study center, sex, and age (±5 years). Diet was assessed using a validated food frequency questionnaire. Intake of prebiotic fibers, namely ITF, total and specific FOS (kestose, nystose and fructofuranosyl-nystose), total and specific GOS (stachyose and raffinose) was estimated using ad hoc composition databases. Energy intake was derived from the Italian food composition database for epidemiological studies.

Using a logistic regression model conditioned on the matching variables and including terms for education (<7, 7-11, ≥12 years) and energy intake tertiles, we estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) of CRC for sex-specific tertiles of prebiotic intake (computed on controls). We also estimated the OR for an increment of one SD of prebiotics. P values for trend across tertiles were computed through the Wald χ² test. Analyses were additionally stratified by cancer site and sex.

RESULTS
Higher intake of selected prebiotic fibers was associated with lower CRC risk. Nystose showed an inverse association for the highest versus lowest tertile (OR 0.44; 95% CI 0.22–0.89), with a significant trend across tertiles. Raffinose was inversely associated (continuous OR 0.63; 95% CI 0.43–0.91), with a stronger inverse association for rectal cancer (OR 0.30; 95% CI 0.15–0.63). No consistent associations were observed for the other prebiotics.

In stratified analyses, for nystose an inverse association was observed in males (OR 0.55; 95% CI 0.43–0.89) but not in females (OR 0.95; 95% CI 0.61–1.47; p-heterogeneity = 0.053). Conversely, for stachyose, an inverse association was found in females (OR 0.53; 95% CI 0.31–0.90) but not in males (OR 1.24; 95% CI 0.92–1.66; p-heterogeneity = 0.010).

CONCLUSIONS

Nystose and raffinose were inversely associated with overall CRC risk, and raffinose showed an inverse association with rectal cancer. Sex-specific inverse associations were observed for nystose and stachyose. These findings support a potential role of selected prebiotic fibers in CRC etiology.