Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort
Couplée aux données de la cohorte européenne EPIC incluant 1 065 patients atteints d'un cancer colorectal (667 cas de cancer du côlon, 398 cas de cancer du rectum) et portant sur 1 065 témoins, cette étude prospective évalue l'association entre le niveau sérique de lipopolysaccharide et de flagelline et le risque de cancer colorectal
Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer (CRC) development. These processes may be contributed to by leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and CRC risk. Methods: 1,065 incident CRC cases (colon n=667; rectal n=398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors. Results: Overall, elevated anti-LPS and anti-flagellin biomarker levels were not associated with CRC risk. After testing potential interactions by various factors relevant for CRC risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (pinteraction < 0.05 for all the biomarkers). Analyses stratified by sex showed a statistically significant positive CRC risk association for men (fully-adjusted OR for highest vs. lowest quartile for total anti-LPS+flagellin = 1.66; 95% CI, 1.10-2.51; ptrend = 0.049) while a borderline statistically significant inverse association was observed for women (fully-adjusted OR= 0.70; 95%CI, 0.47-1.02; ptrend = 0.18). Conclusions: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to CRC risk among men while in women, a possible inverse association may exist. Impact: Further studies are warranted to better clarify these preliminary observations.