Fibroblast growth factor 21 as a circulating biomarker at various stages of colorectal carcinogenesis

BACKGROUND: Despite evidence that inflammation and metabolism play a crucial role in colorectal carcinogenesis, there have been few studies on the association of inflammatory and metabolic protein biomarkers in various stages of colorectal carcinogenesis. METHODS: Ninety-two inflammatory and metabolic biomarkers were measured in plasma samples of participants of screening colonoscopy. Markers identified to be significantly associated with the presence of advanced colorectal neoplasia (ACN) in a discovery set (n = 204) were validated in an independent replication set (n = 422). Adjusted associations with the presence of non-advanced adenomas (NAA), advanced precancerous lesions (APL) and colorectal cancer (CRC) were quantified by multiple logistic regression. RESULTS: Out of the 92 inflammatory proteins, 72 markers were evaluable and 8 showed statistically significant associations with the odds of ACN after full adjustment for potential risk factors for CRC in the discovery set. One of these, fibroblast growth factor 21 (FGF-21), could be validated in the replication set. The multivariable-adjusted odds ratio (OR) reached 2.65 (95% CI, 1.50–4.81) for individuals with FGF-21 levels within the highest tertile, compared to those within the lowest tertile (P(trend) across tertiles = 0.001). Separate models revealed fully adjusted ORs for NAA, APL and CRC of 2.99 (95% CI, 1.45–6.58, P(trend) = 0.005), 2.24 (95% CI, 1.18–4.44, P(trend) = 0.021) and 3.92 (95% CI, 1.51–12.18, P(trend) = 0.003), respectively. CONCLUSIONS: Circulating FGF-21 level is associated with increased risk of early and late stages of colorectal carcinogenesis, supporting a role of inflammation and metabolism at all stages of colorectal carcinogenesis, and suggesting potential use of this biomarker for risk stratification in CRC screening.